Psychopathology in adolescents with TLE and FLE.

PubMed

Huemer, Julia; Plattner, Belinda; Planer, Nadja; Steiner, Hans; Feucht, Martha

2016-11-01

To describe the rates and types of psychiatric disorders among adolescents with chronic symptomatic epilepsies and to evaluate syndrome-specific differences between temporal lobe (TLE) and frontal lobe (FLE) epilepsies. A cross-sectional single-center study design applying the Youth Self Report (YSR) to investigate psychopathological symptoms and the Weinberger Adjustment Inventory (WAI) to investigate personality dimensions was used. Consecutive adolescents between 14 and 18 years of age with drug-resistant symptomatic TLE and FLE were investigated during pre-surgical evaluation prior to epilepsy surgery. Data from twenty-eight patients (19 with TLE and 9 with FLE) were analyzed for this report. Compared with the test norm, higher prevalence rates and a wider range of psychopathological symptoms were seen in patients with TLE. This result was not seen in patients with FLE. Concerning personality dimensions, significantly higher values of repressive defensiveness and significantly lower values of positive emotion and confidence were found in patients with TLE. In contrast, significantly lower levels of distress and significantly higher levels of repressive defensiveness and denial of distress were seen in patients with FLE. Comparing TLE with FLE, a significantly higher mean score for distress, and a significantly lower mean score for positive emotion and denial of distress were found in patients with TLE. In summary, psychiatric comorbidity was frequently found in this sample of youths with chronic drug-resistant localization-related epilepsies. Although results have to be interpreted with caution because of the small sample size, psychiatric symptomatology was significantly different between TLE and FLE. Our results show that continuous and syndrome-specific psychiatric monitoring is essential in young patients with epilepsy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Graph theory findings in the pathophysiology of temporal lobe epilepsy

PubMed Central

Chiang, Sharon; Haneef, Zulfi

2014-01-01

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE. PMID:24831083

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2014-09-01

Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Traumatic Brain Injury (TBI) is a well-established inducer of temporal lobe epilepsy (TLE...INTRODUCTION: This research addresses the FY10 PRMRP topic area of Epilepsy . Traumatic Brain Injury (TBI) is a well- established etiology of temporal ... lobe epilepsy (TLE), a frequently medically intractable and often progressive epilepsy syndrome. Much evidence indicates that abnormalities in

Spectroscopic imaging of the pilocarpine model of human epilepsy suggests that early NAA reduction predicts epilepsy.

PubMed

Gomes, W A; Lado, F A; de Lanerolle, N C; Takahashi, K; Pan, C; Hetherington, H P

2007-08-01

Reduced hippocampal N-acetyl aspartate (NAA) is commonly observed in patients with advanced, chronic temporal lobe epilepsy (TLE). It is unclear, however, whether an NAA deficit is also present during the clinically quiescent latent period that characterizes early TLE. This question has important implications for the use of MR spectroscopic imaging (MRSI) in the early identification of patients at risk for TLE. To determine whether NAA is diminished during the latent period, we obtained high-resolution (1)H spectroscopic imaging during the latent period of the rat pilocarpine model of human TLE. We used actively detuneable surface reception and volume transmission coils to enhance sensitivity and a semiautomated voxel shifting method to accurately position voxels within the hippocampi. During the latent period, 2 and 7 d following pilocarpine treatment, hippocampal NAA was significantly reduced by 27.5 +/- 6.9% (P < 0.001) and 17.3 +/- 6.9% (P < 0.001) at 2 and 7 d, respectively. Quantitative estimates of neuronal loss at 7 d (2.3 +/- 7.7% reduction; P = 0.58, not significant) demonstrate that the NAA deficit is not due to neuron loss and therefore likely represents metabolic impairment of hippocampal neurons during the latent phase. Therefore, spectroscopic imaging provides an early marker for metabolic dysfunction in this model of TLE.

T2 hyperintense signal in patients with temporal lobe epilepsy with MRI signs of hippocampal sclerosis and in patients with temporal lobe epilepsy with normal MRI.

PubMed

Kubota, Bruno Yukio; Coan, Ana Carolina; Yasuda, Clarissa Lin; Cendes, Fernando

2015-05-01

Increased MRI T2 signal is commonly present not only in the hippocampus but also in other temporal structures of patients with temporal lobe epilepsy (TLE), and it is associated with histological abnormalities related to the epileptogenic lesion. This study aimed to verify the distribution of T2 increased signal in temporal lobe structures and its correlations with clinical characteristics of TLE patients with (TLE-HS) or without (TLE-NL) MRI signs of hippocampal sclerosis. We selected 203 consecutive patients: 124 with TLE-HS and 79 with TLE-NL. Healthy controls (N=59) were used as a comparison group/comparative group. T2 multiecho images obtained via a 3-T MRI were evaluated with in-house software. T2 signal decays were computed from five original echoes in regions of interest in the hippocampus, amygdala, and white matter of the anterior temporal lobe. Values higher than 2 standard deviations from the mean of controls were considered as abnormal. T2 signal increase was observed in the hippocampus in 78% of patients with TLE-HS and in 17% of patients with TLE-NL; in the amygdala in 13% of patients with TLE-HS and in 14% of patients with TLE-NL; and in the temporal lobe white matter in 22% of patients with TLE-HS and in 8% of patients with TLE-NL. Group analysis demonstrated a significant difference in the distribution of the T2 relaxation times of the hippocampus (ANOVA, p<0.0001), amygdala (p=0.003), and temporal lobe white matter (p<0.0001) ipsilateral to the epileptogenic zone for patients with TLE-HS compared with controls but only for the amygdala (p=0.029) and temporal lobe white matter (ANOVA, p=0.025) for patients with TLE-NL compared with controls. The average signal from the hippocampus ipsilateral to the epileptogenic zone was significantly higher in patients with no family history of epilepsy (two-sample T-test, p=0.005). Increased T2 signal occurs in different temporal structures of patients with TLE-HS and in patients with TLE-NL. The hippocampal hyperintense signal is more pronounced in patients without family history of epilepsy and is influenced by earlier seizure onset. These changes in T2 signal may be associated with structural abnormalities related to the epileptogenic zone or to the nature of the initial precipitating injury in patients with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center.

PubMed

Hirfanoglu, Tugba; Serdaroglu, Ayse; Kurt, Gokhan; Erdem, Atilla; Capraz, Irem; Bilir, Erhan; Vural, Ozge; Ucar, Murat; Oner, Ali Yusuf; Onal, Baran; Akdemir, Ozgur; Atay, Ozlem; Arhan, Ebru; Aydin, Kursad

2016-10-01

This study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom. This study included 61 children aged between 2 and 18years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom. Of the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p<0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia. Resective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased functional connectivity and structural deficit in alertness network with right-sided temporal lobe epilepsy.

PubMed

Gao, Yujun; Zheng, Jinou; Li, Yaping; Guo, Danni; Wang, Mingli; Cui, Xiangxiang; Ye, Wei

2018-04-01

Patients with temporal lobe epilepsy (TLE) often suffer from alertness alterations. However, specific regions connected with alertness remain controversial, and whether these regions have structural impairment is also elusive. This study aimed to investigate the characteristics and neural mechanisms underlying the functions and structures of alertness network in patients with right-sided temporal lobe epilepsy (rTLE) by performing the attentional network test (ANT), resting-state functional magnetic resonance imaging (R-SfMRI), and diffusion tensor imaging (DTI).A total of 47 patients with rTLE and 34 healthy controls underwent ANT, R-SfMRI, and DTI scan. The seed-based functional connectivity (FC) method and deterministic tractography were used to analyze the data.Patients with rTLE had longer reaction times in the no-cue and double-cue conditions. However, no differences were noted in the alertness effect between the 2 groups. The patient group had lower FC compared with the control group in the right inferior parietal lobe (IPL), amygdala, and insula. Structural deficits were found in the right parahippocampal gyrus, superior temporal pole, insula, and amygdala in the patient group compared with the control group. Also significantly negative correlations were observed between abnormal fractional anisotropy (between the right insula and the superior temporal pole) and illness duration in the patients with rTLE.The findings of this study suggested abnormal intrinsic and phasic alertness, decreased FC, and structural deficits within the alerting network in the rTLE. This study provided new insights into the mechanisms of alertness alterations in rTLE.

Impaired cerebral blood flow networks in temporal lobe epilepsy with hippocampal sclerosis: A graph theoretical approach.

PubMed

Sone, Daichi; Matsuda, Hiroshi; Ota, Miho; Maikusa, Norihide; Kimura, Yukio; Sumida, Kaoru; Yokoyama, Kota; Imabayashi, Etsuko; Watanabe, Masako; Watanabe, Yutaka; Okazaki, Mitsutoshi; Sato, Noriko

2016-09-01

Graph theory is an emerging method to investigate brain networks. Altered cerebral blood flow (CBF) has frequently been reported in temporal lobe epilepsy (TLE), but graph theoretical findings of CBF are poorly understood. Here, we explored graph theoretical networks of CBF in TLE using arterial spin labeling imaging. We recruited patients with TLE and unilateral hippocampal sclerosis (HS) (19 patients with left TLE, and 21 with right TLE) and 20 gender- and age-matched healthy control subjects. We obtained all participants' CBF maps using pseudo-continuous arterial spin labeling and analyzed them using the Graph Analysis Toolbox (GAT) software program. As a result, compared to the controls, the patients with left TLE showed a significantly low clustering coefficient (p=0.024), local efficiency (p=0.001), global efficiency (p=0.010), and high transitivity (p=0.015), whereas the patients with right TLE showed significantly high assortativity (p=0.046) and transitivity (p=0.011). The group with right TLE also had high characteristic path length values (p=0.085), low global efficiency (p=0.078), and low resilience to targeted attack (p=0.101) at a trend level. Lower normalized clustering coefficient (p=0.081) in the left TLE and higher normalized characteristic path length (p=0.089) in the right TLE were found also at a trend level. Both the patients with left and right TLE showed significantly decreased clustering in similar areas, i.e., the cingulate gyri, precuneus, and occipital lobe. Our findings revealed differing left-right network metrics in which an inefficient CBF network in left TLE and vulnerability to irritation in right TLE are suggested. The left-right common finding of regional decreased clustering might reflect impaired default-mode networks in TLE. Copyright © 2016 Elsevier Inc. All rights reserved.

Seizure semiology and electroencephalography in young children with lesional temporal lobe epilepsy.

PubMed

Lv, Rui-Juan; Sun, Zhen-Rong; Cui, Tao; Shao, Xiao-Qiu

2014-02-01

This study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE). Children with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE. A total of 84 seizures were analyzed in 11 children (aged 23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early. In contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Stem cell therapy for treatment of epilepsy.

PubMed

Goodarzi, Parisa; Aghayan, Hamid Reza; Soleimani, Masoud; Norouzi-Javidan, Abbas; Mohamadi-Jahani, Fereshteh; Jahangiri, Sharareh; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak

2014-01-01

Epilepsy as one of the most common neurological disorders affects more than 50 million people worldwide with a higher prevalence rate in low-income countries. Excessive electrical discharges in neurons following neural cell damage or loss cause recurrent seizures. One of the most common and difficult to treat types of epilepsy is temporal lobe epilepsy (TLE) which results from hippocampal sclerosis. Nowadays, similar to other diseases, epilepsy also is a candidate for treatment with different types of stem cells. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. Two major roles of stem cell therapy in epilepsy are prophylaxis against chronic epilepsy and amelioration cognitive function after the occurrence of TLE. Several animal studies have supported the use of these cells for treating drug-resistant TLE. Although stem cell therapy seems like a promising approach for treatment of epilepsy in the future however, there are some serious safety and ethical concerns that are needed to be eliminated before clinical application.

Temporal lobe epilepsy is a predisposing factor for sleep apnea: A questionnaire study in video-EEG monitoring unit.

PubMed

Yildiz, F Gokcem; Tezer, F Irsel; Saygi, Serap

2015-07-01

The interaction between epilepsy and sleep is known. It has been shown that patients with epilepsy have more sleep problems than the general population. However, there is no recent study that compares the frequency of sleep disorders in groups with medically refractory temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). The main purpose of this study was to investigate the occurrence of sleep disorders in two subtypes of epilepsy by using sleep questionnaire forms. One hundred and eighty-nine patients, out of 215 who were monitored for refractory epilepsy and were followed by the video-EEG monitoring unit, were divided into a group with TLE and a group with ETLE. The medical outcome study-sleep scale (MOS-SS), Epworth sleepiness scale (ESS), and sleep apnea scale of the sleep disorders questionnaire (SD-SDQ) were completed after admission to the video-EEG monitoring unit. The total scores in the group with TLE and group with ETLE were compared. Of the patients, TLE was diagnosed in 101 (53.4%) (45 females), and ETLE was diagnosed in 88 (46.6%) (44 females). Comparison of MOS-SS and Epworth sleepiness scale scores in the two subgroups did not reveal significant differences. In the group with TLE, SD-SDQ scores were significantly higher compared to that in the group with ETLE. Patients with temporal lobe epilepsy have higher risk of obstructive sleep apnea (OSA) according to their reported symptoms. Detection of OSA in patients with epilepsy by using questionnaire forms may decrease the risk of ictal or postictal respiratory-related 'Sudden Unexpected Death in Epilepsy'. Copyright © 2015 Elsevier Inc. All rights reserved.

Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions

PubMed Central

Laufs, Helmut; Hamandi, Khalid; Salek-Haddadi, Afraim; Kleinschmidt, Andreas K; Duncan, John S; Lemieux, Louis

2007-01-01

A cerebral network comprising precuneus, medial frontal, and temporoparietal cortices is less active both during goal-directed behavior and states of reduced consciousness than during conscious rest. We tested the hypothesis that the interictal epileptic discharges affect activity in these brain regions in patients with temporal lobe epilepsy who have complex partial seizures. At the group level, using electroencephalography-correlated functional magnetic resonance imaging in 19 consecutive patients with focal epilepsy, we found common decreases of resting state activity in 9 patients with temporal lobe epilepsy (TLE) but not in 10 patients with extra-TLE. We infer that the functional consequences of TLE interictal epileptic discharges are different from those in extra-TLE and affect ongoing brain function. Activity increases were detected in the ipsilateral hippocampus in patients with TLE, and in subthalamic, bilateral superior temporal and medial frontal brain regions in patients with extra-TLE, possibly indicating effects of different interictal epileptic discharge propagation. PMID:17133385

Lateralization of temporal lobe epilepsy and learning disabilities, as defined by disability-related civil rights law.

PubMed

Butterbaugh, Grant; Olejniczak, Piotr; Roques, Betsy; Costa, Richard; Rose, Marcy; Fisch, Bruce; Carey, Michael; Thomson, Jessica; Skinner, John

2004-08-01

Epilepsy research has identified higher rates of learning disorders in patients with temporal lobe epilepsy (TLE). However, most studies have not adequately assessed complex functional adult learning skills, such as reading comprehension and written language. We designed this study to evaluate our predictions that higher rates of reading comprehension, written language, and calculation disabilities would be associated with left TLE versus right TLE. Reading comprehension, written language, and calculation skills were assessed by using selected subtests from the Woodcock-Johnson Psycho-Educational Tests of Achievement-Revised in a consecutive series of 31 presurgical patients with TLE. Learning disabilities were defined by one essential criterion consistent with the Americans with Disabilities Act of 1990. Patients had left hemisphere language dominance based on Wada results, left or right TLE based on inpatient EEG monitoring, and negative magnetic resonance imaging (MRI), other than MRI correlates of mesial temporal sclerosis. Higher rates of reading comprehension, written language, and calculation disabilities were associated with left TLE, as compared with right TLE. Nearly 75% of patients with left TLE, whereas fewer than 10% of those with right TLE, had at least one learning disability. Seizure onset in the language-dominant hemisphere, as compared with the nondominant hemisphere, was associated with higher rates of specific learning disabilities and a history of poor literacy or career development or both. These results support the potential clinical benefits of using lateralization of seizure onset as a predictor of the risk of learning disabilities that, once evaluated, could be accommodated to increase the participation of patients with epilepsy in work and educational settings.

Temporal Lobe Epilepsy Alters Auditory-motor Integration For Voice Control

PubMed Central

Li, Weifeng; Chen, Ziyi; Yan, Nan; Jones, Jeffery A.; Guo, Zhiqiang; Huang, Xiyan; Chen, Shaozhen; Liu, Peng; Liu, Hanjun

2016-01-01

Temporal lobe epilepsy (TLE) is the most common drug-refractory focal epilepsy in adults. Previous research has shown that patients with TLE exhibit decreased performance in listening to speech sounds and deficits in the cortical processing of auditory information. Whether TLE compromises auditory-motor integration for voice control, however, remains largely unknown. To address this question, event-related potentials (ERPs) and vocal responses to vocal pitch errors (1/2 or 2 semitones upward) heard in auditory feedback were compared across 28 patients with TLE and 28 healthy controls. Patients with TLE produced significantly larger vocal responses but smaller P2 responses than healthy controls. Moreover, patients with TLE exhibited a positive correlation between vocal response magnitude and baseline voice variability and a negative correlation between P2 amplitude and disease duration. Graphical network analyses revealed a disrupted neuronal network for patients with TLE with a significant increase of clustering coefficients and path lengths as compared to healthy controls. These findings provide strong evidence that TLE is associated with an atypical integration of the auditory and motor systems for vocal pitch regulation, and that the functional networks that support the auditory-motor processing of pitch feedback errors differ between patients with TLE and healthy controls. PMID:27356768

Graph theory findings in the pathophysiology of temporal lobe epilepsy.

PubMed

Chiang, Sharon; Haneef, Zulfi

2014-07-01

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Social cognition dysfunctions in patients with epilepsy: Evidence from patients with temporal lobe and idiopathic generalized epilepsies.

PubMed

Realmuto, Sabrina; Zummo, Leila; Cerami, Chiara; Agrò, Luigi; Dodich, Alessandra; Canessa, Nicola; Zizzo, Andrea; Fierro, Brigida; Daniele, Ornella

2015-06-01

Despite an extensive literature on cognitive impairments in focal and generalized epilepsy, only a few number of studies specifically explored social cognition disorders in epilepsy syndromes. The aim of our study was to investigate social cognition abilities in patients with temporal lobe epilepsy (TLE) and in patients with idiopathic generalized epilepsy (IGE). Thirty-nine patients (21 patients with TLE and 18 patients with IGE) and 21 matched healthy controls (HCs) were recruited. All subjects underwent a basic neuropsychological battery plus two experimental tasks evaluating emotion recognition from facial expression (Ekman-60-Faces test, Ek-60F) and mental state attribution (Story-based Empathy Task, SET). In particular, the latter is a newly developed task that assesses the ability to infer others' intentions (i.e., intention attribution - IA) and emotions (i.e., emotion attribution - EA) compared with a control condition of physical causality (i.e., causal inferences - CI). Compared with HCs, patients with TLE showed significantly lower performances on both social cognition tasks. In particular, all SET subconditions as well as the recognition of negative emotions were significantly impaired in patients with TLE vs. HCs. On the contrary, patients with IGE showed impairments on anger recognition only without any deficit at the SET task. Emotion recognition deficits occur in patients with epilepsy, possibly because of a global disruption of a pathway involving frontal, temporal, and limbic regions. Impairments of mental state attribution specifically characterize the neuropsychological profile of patients with TLE in the context of the in-depth temporal dysfunction typical of such patients. Impairments of socioemotional processing have to be considered as part of the neuropsychological assessment in both TLE and IGE in view of a correct management and for future therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Exome sequencing identifies SUCO mutations in mesial temporal lobe epilepsy.

PubMed

Sha, Zhiqiang; Sha, Longze; Li, Wenting; Dou, Wanchen; Shen, Yan; Wu, Liwen; Xu, Qi

2015-03-30

Mesial temporal lobe epilepsy (mTLE) is the main type and most common medically intractable form of epilepsy. Severity of disease-based stratified samples may help identify new disease-associated mutant genes. We analyzed mRNA expression profiles from patient hippocampal tissue. Three of the seven patients had severe mTLE with generalized-onset convulsions and consciousness loss that occurred over many years. We found that compared with other groups, patients with severe mTLE were classified into a distinct group. Whole-exome sequencing and Sanger sequencing validation in all seven patients identified three novel SUN domain-containing ossification factor (SUCO) mutations in severely affected patients. Furthermore, SUCO knock down significantly reduced dendritic length in vitro. Our results indicate that mTLE defects may affect neuronal development, and suggest that neurons have abnormal development due to lack of SUCO, which may be a generalized-onset epilepsy-related gene. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

PubMed Central

Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

2014-01-01

Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated. PMID:23530853

Left or right? Lateralizing temporal lobe epilepsy by dynamic amygdala fMRI.

PubMed

Ives-Deliperi, Victoria; Butler, James Thomas; Jokeit, Hennric

2017-05-01

In this case series, the findings of 85 functional MRI studies employing a dynamic fearful face paradigm are reported. Previous findings have shown the paradigm to generate bilateral amygdala activations in healthy subjects and unilateral activations in patients with MTLE, in the contralateral hemisphere to seizure origin. Such findings suggest ipsilateral limbic pathology and offer collateral evidence in lateralizing MTLE. The series includes 60 patients with TLE, 12 patients with extra-temporal lobe epilepsy, and 13 healthy controls. Functional MRI studies using a 1.5T scanner were conducted over a three-year period at a single epilepsy center and individual results were compared with EEG findings. In the cohort of unilateral TLE patients, lateralized activations of the amygdala were concordant with EEG findings in 76% of patients (77% lTLE, 74% rTLE). The differences in the mean lateralized indices of the lTLE, rTLE, and healthy control groups were all statistically significant. Lateralized amygdala activations were concordant with EEG findings in only 31% of the 12 patients with extra-temporal lobe epilepsy and bilateral amygdala activations were generated in all but one of the healthy control subjects. This case series further endorses the utility of the dynamic fearful face functional MRI paradigm using the widely available 1.5T as an adjunctive investigation to lateralize TLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Object and proper name retrieval in temporal lobe epilepsy: a study of difficulties and latencies.

PubMed

Condret-Santi, Valérie; Barragan-Jason, Gladys; Valton, Luc; Denuelle, Marie; Curot, Jonathan; Nespoulous, Jean-Luc; Barbeau, Emmanuel J

2014-12-01

Retrieving a specific name is sometimes difficult and can be even harder when pathology affects the temporal lobes. Word finding difficulties have been well documented in temporal lobe epilepsy (TLE) but analyses have mostly concentrated on the study of accuracy. Our aim here was to go beyond simple accuracy and to provide both a quantitative and a qualitative assessment of naming difficulties and latencies in patients with TLE. Thirty-two patients with temporal lobe epilepsy (16 with epilepsy affecting the cerebral hemisphere dominant for language (D-TLE) and 16 with epilepsy affecting the cerebral hemisphere non-dominant for language (ND-TLE)) and 34 healthy matched control subjects were included in the study. The experiment involved naming 70 photographs of objects and 70 photographs of celebrities as fast as possible. Accuracy and naming reaction times were recorded. Following each trial, a questionnaire was used to determine the specific nature of each subject's difficulty in retrieving the name (e.g., no difficulty, paraphasia, tip of the tongue, feeling of knowing the name, etc). Reaction times were analysed both across subjects and across trials. D-TLE patients showed consistent and quasi-systematic impairment compared to matched control subjects on both object and famous people naming. This impairment was characterized not only by lower accuracy but also by more qualitative errors and tip of the tongue phenomena. Furthermore, minimum reaction times were slowed down by about 70 ms for objects and 150 ms for famous people naming. In contrast, patients with ND-TLE were less impaired, and their impairment was limited to object naming. These results suggest that patients with TLE, in particular D-TLE, show a general impairment of lexical access. Furthermore, there was evidence of subtle difficulties (increased reaction times) in patients with TLE. Copyright © 2014 Elsevier B.V. All rights reserved.

Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy

PubMed Central

Sidhu, M.K.; Stretton, J.; Winston, G.P.; Symms, M.; Thompson, P.J.; Koepp, M.J.; Duncan, J.S.

2015-01-01

Summary Aims In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. Methods We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. Results Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. Conclusion Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation. PMID:25616449

Video electroencephalogram telemetry in temporal lobe epilepsy

PubMed Central

Mani, Jayanti

2014-01-01

Temporal lobe epilepsy (TLE) is the most commonly encountered medically refractory epilepsy. It is also the substrate of refractory epilepsy that gives the most gratifying results in any epilepsy surgery program, with a minimum use of resources. Correlation of clinical behavior and the ictal patterns during ictal behavior is mandatory for success at epilepsy surgery. Video electroencephalogram (EEG) telemetry achieves this goal and hence plays a pivotal role in pre-surgical assessment. The role of telemetry is continuously evolving with the advent of digital EEG technology, of high-resolution volumetric magnetic resonance imaging and other functional imaging techniques. Most of surgical selection in patients with TLE can be done with a scalp video EEG monitoring. However, the limitations of the scalp EEG technique demand invasive recordings in a selected group of TLE patients. This subset of the patients can be a challenge to the epileptologist. PMID:24791089

Isolated amygdala enlargement in temporal lobe epilepsy: A systematic review.

PubMed

Beh, S M Jessica; Cook, Mark J; D'Souza, Wendyl J

2016-07-01

The objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies. PubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords 'amygdala enlargement', 'epilepsy', and 'seizures' in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included. Of 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small samples of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67-100% vs. 26-47%), and they have an excellent response to antiepileptic drugs (81.8%-100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls. Reliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests characteristics of an older age of epilepsy onset, a greater tendency to nonconvulsive seizures, and a good response to antiepileptic drugs in this interesting group of epilepsies. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Clinical correlates of graph theory findings in temporal lobe epilepsy.

PubMed

Haneef, Zulfi; Chiang, Sharon

2014-11-01

Temporal lobe epilepsy (TLE) is considered a brain network disorder, additionally representing the most common form of pharmaco-resistant epilepsy in adults. There is increasing evidence that seizures in TLE arise from abnormal epileptogenic networks, which extend beyond the clinico-radiologically determined epileptogenic zone and may contribute to the failure rate of 30-50% following epilepsy surgery. Graph theory allows for a network-based representation of TLE brain networks using several neuroimaging and electrophysiologic modalities, and has potential to provide clinicians with clinically useful biomarkers for diagnostic and prognostic purposes. We performed a review of the current state of graph theory findings in TLE as they pertain to localization of the epileptogenic zone, prediction of pre- and post-surgical seizure frequency and cognitive performance, and monitoring cognitive decline in TLE. Although different neuroimaging and electrophysiologic modalities have yielded occasionally conflicting results, several potential biomarkers have been characterized for identifying the epileptogenic zone, pre-/post-surgical seizure prediction, and assessing cognitive performance. For localization, graph theory measures of centrality have shown the most potential, including betweenness centrality, outdegree, and graph index complexity, whereas for prediction of seizure frequency, measures of synchronizability have shown the most potential. The utility of clustering coefficient and characteristic path length for assessing cognitive performance in TLE is also discussed. Future studies integrating data from multiple modalities and testing predictive models are needed to clarify findings and develop graph theory for its clinical utility. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Impaired Facial Expression Recognition in Children with Temporal Lobe Epilepsy: Impact of Early Seizure Onset on Fear Recognition

ERIC Educational Resources Information Center

Golouboff, Nathalie; Fiori, Nicole; Delalande, Olivier; Fohlen, Martine; Dellatolas, Georges; Jambaque, Isabelle

2008-01-01

The amygdala has been implicated in the recognition of facial emotions, especially fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE). The present study investigates the recognition of facial emotions in children and adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right, 16 left) and…

Attention deficits in children with epilepsy: Preliminary findings.

PubMed

Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

2017-02-01

Attention difficulties are a common clinical complaint among children with epilepsy. We aimed to compare a range of attentional abilities between groups of children with two common epilepsy syndromes, Temporal Lobe Epilepsy (TLE) and Idiopathic Generalized Epilepsy (IGE), and to healthy controls. We also investigated whether epilepsy factors (laterality of seizure focus, epilepsy onset, duration, and severity) were related to attentional abilities. Multiple dimensions of attention (selective, sustained, and divided attention and attentional control) were assessed directly with standardized neuropsychological measures in 101 children aged 6-16years (23 children with TLE, 20 with IGE and 58 healthy controls). Attention was also assessed indirectly, via a parent-report measure. Children with TLE performed worse than children with IGE (p=0.013) and healthy controls (p<0.001) on a test of attentional control, but no between-group differences were apparent on tests of other attentional abilities. Compared to healthy controls, greater attention problems were reported by parents of children with TLE (p=0.006) and IGE (p=0.012). Left-hemisphere seizure focus and greater epilepsy severity were associated with poorer attentional control and sustained-divided attention, respectively, but no other epilepsy factors were associated with attentional abilities. These findings suggest that children with localization-related epilepsy, but not generalized epilepsy, may be at risk of deficits in attentional control. Interventions aimed at improving attentional control may be targeted at children with localization-related epilepsy, particularly those with a left-hemisphere seizure focus, who appear to be particularly susceptible to this type of attentional deficit. Copyright © 2016 Elsevier Inc. All rights reserved.

Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy.

PubMed

Bernhardt, Boris C; Bonilha, Leonardo; Gross, Donald W

2015-09-01

Recent years have witnessed a paradigm shift in the study and conceptualization of epilepsy, which is increasingly understood as a network-level disorder. An emblematic case is temporal lobe epilepsy (TLE), the most common drug-resistant epilepsy that is electroclinically defined as a focal epilepsy and pathologically associated with hippocampal sclerosis. In this review, we will summarize histopathological, electrophysiological, and neuroimaging evidence supporting the concept that the substrate of TLE is not limited to the hippocampus alone, but rather is broadly distributed across multiple brain regions and interconnecting white matter pathways. We will introduce basic concepts of graph theory, a formalism to quantify topological properties of complex systems that has recently been widely applied to study networks derived from brain imaging and electrophysiology. We will discuss converging graph theoretical evidence indicating that networks in TLE show marked shifts in their overall topology, providing insight into the neurobiology of TLE as a network-level disorder. Our review will conclude by discussing methodological challenges and future clinical applications of this powerful analytical approach. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation of LILRB2 signal pathway in temporal lobe epilepsy patients and in a pilocarpine induced epilepsy model.

PubMed

Yue, Jiong; Li, Wei; Liang, Chao; Chen, Bing; Chen, Xin; Wang, Lukang; Zang, Zhenle; Yu, Sixun; Liu, Shiyong; Li, Song; Yang, Hui

2016-11-01

Temporal lobe epilepsy (TLE) is a frequent form of focal intractable epilepsy in adults, but the specific mechanism underlying the epileptogenesis of TLE is still unknown. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) (the murine homolog gene called paired immunoglobulin-like receptor B, or PirB), participates in the process of synaptic plasticity and neurite growth in the central nervous system (CNS), suggesting a potential role of LILRB2 in epilepsy. However, the expression pattern of LILRB2 and the downstream molecular signal in intractable TLE remains poorly understood. In the present study, western blotting and immunohistochemistry results showed that LILRB2 expression was upregulated in the temporal neocortex of patients with TLE. Moreover, protein levels of LILRB2 negatively correlated with the frequency of seizures in TLE patients. In the pilocarpine-induced C57BL/6 mouse model, PirB upregulation in the hippocampus began 12h after status epilepticus (SE), reached a peak at 7days and then maintained a significantly high level until day 60. Similarly, we found a remarkable increase in PirB expression at 1day, 7days and30days post-SE in the temporal cortex. Double-labeled immunofluorescence showed that LILRB2/PirB were highly expressed in neurons and astrocytes but not microglia. In addition, protein levels of POSH, SHROOM3, ROCK1 and ROCK2, the important downstream factors of the LILRB2 pathway, were significantly increased in the epileptic foci of TLE patients and located on the NeuN-positive neurons and GFAP-positive astrocytes. Taken together, our results indicate that LILRB2/PirB may be involved in the process of TLE. Copyright © 2016 Elsevier Inc. All rights reserved.

Immunohistochemical study of Metallothionein in patients with temporal lobe epilepsy.

PubMed

Juárez-Rebollar, Daniel; Alonso-Vanegas, Mario; Nava-Ruíz, Concepción; Buentello-García, Masao; Yescas-Gómez, Petra; Díaz-Ruíz, Araceli; Rios, Camilo; Méndez-Armenta, Marisela

2017-05-01

Epilepsy is characterized by spontaneous recurrent seizures and temporal lobe epilepsy (TLE) is the most common serious neurological example of acquired and frequent epilepsy. Oxidative stress is recognized as playing a contributing role in several neurological disorders, and most recently have been implicated in acquired epilepsies. The MTs occur in several brain regions and may serve as neuroprotective proteins against reactive oxygen species causing oxidative damage and stress. The main aim of this work was to describe the immunohistochemical localization of MT in the specimens derived from the patients affected by TLE. Histopathological examination showed NeuN, GFAP and MT immunopositive cells that were analyzed for determinate in hippocampal and parietal cortex samples. An increase in the reactive gliosis associated with increased MT expression was observed in patients with TLE. Copyright © 2016 Elsevier Ltd. All rights reserved.

De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy.

PubMed

Vari, Maria Stella; Traverso, Monica; Bellini, Tommaso; Madia, Francesca; Pinto, Francesca; Minetti, Carlo; Striano, Pasquale; Zara, Federico

2017-08-01

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and may be associated with acquired central nervous system lesions or could be genetic. Various susceptibility genes and environmental factors are believed to be involved in the aetiology of TLE, which is considered to be a heterogeneous, polygenic, and complex disorder. Rare point mutations in LGI1, DEPDC5, and RELN as well as some copy number variations (CNVs) have been reported in families with TLE patients. We perform a genetic analysis by Array-CGH in a patient with dysmorphic features and temporal lobe epilepsy. We report a de novo duplication of the long arm of chromosome 12. We confirm that 12q22-q23.3 is a candidate locus for familial temporal lobe epilepsy with febrile seizures and highlight the role of chromosomal rearrangements in patients with epilepsy and intellectual disability. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

PubMed Central

Wolfart, Jakob; Laker, Debora

2015-01-01

Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

Novel GABRG2 mutations cause familial febrile seizures

PubMed Central

Boillot, Morgane; Morin-Brureau, Mélanie; Picard, Fabienne; Weckhuysen, Sarah; Lambrecq, Virginie; Minetti, Carlo; Striano, Pasquale; Zara, Federico; Iacomino, Michele; Ishida, Saeko; An-Gourfinkel, Isabelle; Daniau, Mailys; Hardies, Katia; Baulac, Michel; Dulac, Olivier; Leguern, Eric; Nabbout, Rima

2015-01-01

Objective: To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy. Methods: The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening. Results: Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.Pro59fs*12), 1 missense mutation (p.Met199Val), and 1 exonic deletion were subsequently identified in 5 families of the follow-up cohort. Conclusions: We report GABRG2 mutations in 5.6% (6/108) of families with FS, with or without associated epilepsy. This study provides evidence that GABRG2 mutations are linked to the FS phenotype, rather than epilepsy, and that loss-of-function of GABAA receptor γ2 subunit is the probable underlying pathogenic mechanism. PMID:27066572

Epilepsy and restless legs syndrome.

PubMed

Geyer, James D; Geyer, Emery E; Fetterman, Zachary; Carney, Paul R

2017-03-01

Restless legs syndrome (RLS) is a common neurological movement disorder occurring in approximately 10% of the general population. The prevalence of moderately severe RLS is 2.7% overall (3.7% for women and 1.7% for men). Epilepsy is also a common neurological disorder with significant associated morbidity and impact on quality of life. We evaluated the severity and frequency of primary RLS in patients with localization-related temporal lobe epilepsy (TLE) and investigated the role of prodromal RLS symptoms as a warning sign and lateralizing indicator. All epilepsy patients seen in the outpatient clinic were screened for movement disorders from 2005 to 2015. Ninety-eight consecutive patients with localization-related TLE (50 right TLE and 48 left TLE) who met inclusion criteria were seen in the outpatient clinic. The control group consisted of 50 individuals with no history or immediate family history of epilepsy. Each patient was evaluated with the International Restless Legs Study Group (IRLSSG) questionnaire, NIH RLS diagnostic criteria, ferritin level, and comprehensive sleep screening including polysomnography. Furthermore, patients with obstructive sleep apnea or a definite cause of secondary restless legs syndrome such as low serum ferritin or serum iron levels were also excluded from the study. There was a significant association between the type of epilepsy and whether or not patients had RLS χ 2 (1)=10.17, p<.01, using the χ 2 Goodness of Fit Test. Based on the odds ratio, the odds of patients having RLS were 4.60 times higher if they had right temporal epilepsy than if they had left temporal epilepsy, serving as a potential lateralizing indicator. A prodromal sensation of worsening RLS occurred in some patients providing the opportunity to intervene at an earlier stage in this subgroup. We identified frequent moderate to severe RLS in patients with epilepsy. The frequency of RLS was much more common than would typically be seen in patients of similar age. The restlessness was typically described as moderately severe. The RLS symptoms were more common and somewhat more severe in the right TLE group than the left TLE group. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors for spatial memory impairment in patients with temporal lobe epilepsy.

PubMed

Amlerova, Jana; Laczo, Jan; Vlcek, Kamil; Javurkova, Alena; Andel, Ross; Marusic, Petr

2013-01-01

At present, the risk factors for world-centered (allocentric) navigation impairment in patients with temporal lobe epilepsy (TLE) are not known. There is some evidence on the importance of the right hippocampus but other clinical features have not been investigated yet. In this study, we used an experimental human equivalent to the Morris water maze to examine spatial navigation performance in patients with drug-refractory unilateral TLE. We included 47 left-hemisphere speech dominant patients (25 right sided; 22 left sided). The aim of our study was to identify clinical and demographic characteristics of TLE patients who performed poorly in allocentric spatial memory tests. Our results demonstrate that poor spatial navigation is significantly associated with younger age at epilepsy onset, longer disease duration, and lower intelligence level. Allocentric navigation in TLE patients was impaired irrespective of epilepsy lateralization. Good and poor navigators did not differ in their age, gender, or preoperative/postoperative status. This study provides evidence on risk factors that increase the likelihood of allocentric navigation impairment in TLE patients. The results indicate that not only temporal lobe dysfunction itself but also low general cognitive abilities may contribute to the navigation impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

Up-regulated ephrinB3/EphB3 expression in intractable temporal lobe epilepsy patients and pilocarpine induced experimental epilepsy rat model.

PubMed

Huang, Hao; Li, Ruohan; Yuan, Jinxian; Zhou, Xin; Liu, Xi; Ou, Shu; Xu, Tao; Chen, Yangmei

2016-05-15

EphB family receptor tyrosine kinases, in cooperation with cell surface-bound ephrinB ligands, play a critical role in maintenance of dendritic spine morphogenesis, axons guidance, synaptogenesis, synaptic reorganization and plasticity in the central nervous system (CNS). However, the expression pattern of ephrinB/EphB in intractable temporal lobe epilepsy (TLE) and the underlying molecular mechanisms during epileptogenesis remain poorly understood. Here we investigated the expression pattern and cellular distribution of ephrinB/EphB in intractable TLE patients and lithium chloride-pilocarpine induced TLE rats using real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, double-labeled immunofluorescence and Western blot analysis. Compared to control groups, ephrinB3 and EphB3 mRNA expression were significantly up-regulated in intractable TLE patients and TLE rats, while the mRNA expression trend of ephrinB1/2 and EphB1/2/4/6 in intractable TLE patients and TLE rats were inconsistent. Western blot analysis and semi-quantitative immunohistochemistry confirmed that ephrinB3 and EphB3 protein level were up-regulated in intractable TLE patients and TLE rats. At the same time, double-labeled immunofluorescence indicate that ephrinB3 was expressed mainly in the cytoplasm and protrusions of glia and neurons, while EphB3 was expressed mainly in the cytoplasm of neurons. Taken together, up-regulated expression of ephrinB3/EphB3 in intractable TLE patients and experimental TLE rats suggested that ephrinB3/EphB3 might be involved in the pathogenesis of TLE. Copyright © 2016 Elsevier B.V. All rights reserved.

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy.

PubMed

Loi, Richard Q; Leyden, Kelly M; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J; Paul, Brianna M; Dale, Anders M; White, Nathan S; McDonald, Carrie R

2016-11-01

Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers). RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Reductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy.

PubMed

Torres, Carolina Machado; Siebert, Marina; Bock, Hugo; Mota, Suelen Mandelli; Castan, Juliana Unis; Scornavacca, Francisco; de Castro, Luiza Amaral; Saraiva-Pereira, Maria Luiza; Bianchin, Marino Muxfeldt

2017-06-01

Psychiatric comorbidities are highly prevalent in epilepsy, adding an important burden to the disease and profoundly affecting the quality of life of these individuals. Patients with temporal lobe epilepsy (TLE) are especially at risk to develop depression and several lines of evidence suggest that the association of depression with epilepsy might be related to common biological substrates. In this study, we test whether NTRK2 allele variants are associated with mood disorders or depressive disorders in patients with TLE. An association study of 163 patients with TLE. The NTRK2 variants studied were rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. All patients were submitted to the Structured Clinical Interview for DSM-IV (SCID) and epilepsy patients with mood disorders or depressive disorders were compared to epilepsy patients without mood disorders or depressive disorders. In our TLE cohort, 76 patients (46.6%) showed mood disorders. After logistic regression, independent risk factors for mood disorders in TLE were female sex, presence of concomitant anxiety disorders, and genetic variations in rs1867283 and rs10868235 NTRK2 variants. Depressive disorders accounted for this results and independent variables associated with depressive disorders in TLE were female sex (OR=2.59; 95%CI=1.15-5.82; p=0.021), presence of concomitant anxiety disorders (OR=3.72; 95%CI=1.71-8.06; p=0.001) or psychotic disorders (OR=3.86; 95%CI=1.12-13.25; p=0.032), A/A genotype in the rs1867283 NTRK2 gene (OR=3.06; 95%CI=1.25-7.50; p=0.015) and C/C genotype in the rs10868235 NTRK2 gene (OR=3.54; 1.55-8.08; p=0.003). Similarly, these genotypes also remained independently and significantly associated with depressive disorders when patients with depressive disorders were compared to TLE patients without any psychiatric comorbidity. In the present study, female sex, presence of concomitant anxiety or psychotic disorders, and specific allelic variations in the NTRK2 gene were independently associated with mood disorders or depressive disorders in TLE. If our results were confirmed, variants in the NTRK2 gene could be considered as risk factors or biomarkers for depressive disorders in patients with TLE. Copyright © 2017 Elsevier Inc. All rights reserved.

High-frequency oscillations, extent of surgical resection, and surgical outcome in drug-resistant focal epilepsy

PubMed Central

Haegelen, Claire; Perucca, Piero; Châtillon, Claude-Edouard; Andrade-Valença, Luciana; Zelmann, Rina; Jacobs, Julia; Collins, D. Louis; Dubeau, François; Olivier, André; Gotman, Jean

2013-01-01

Summary Purpose Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome. Methods We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow-up was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80–250 Hz; fast ripples, >250 Hz) were identified visually on a 5–10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome. Key Findings HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome. Significance In TLE, removal of HFO-generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results. PMID:23294353

Historical Risk Factors Associated with Seizure Outcome After Surgery for Drug-Resistant Mesial Temporal Lobe Epilepsy.

PubMed

Asadi-Pooya, Ali A; Nei, Maromi; Sharan, Ashwini; Sperling, Michael R

2016-05-01

To investigate the possible influence of risk factors on seizure outcome after surgery for drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). This retrospective study recruited patients with drug-resistant MTS-TLE who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center and were followed for a minimum of 1 year. Patients had been prospectively registered in a database from 1986 through 2014. After surgery outcome was classified into 2 groups: seizure-free or relapsed. The possible risk factors influencing long-term outcome after surgery were investigated. A total of 275 patients with MTS-TLE were studied. Two thirds of the patients had Engel's class 1 outcome and 48.4% of the patients had sustained seizure freedom, with no seizures since surgery. Patients with a history of tonic-clonic seizures in the year preceding surgery were more likely to experience seizure recurrence (odds ratio, 2.4; 95% confidence interval 1.19-4.80; P = 0.01). Gender, race, family history of epilepsy, history of febrile seizure, history of status epilepticus, duration of disease before surgery, intelligence quotient, and seizure frequency were not predictors of outcome. Many patients with drug-resistant MTS-TLE respond favorably to surgery. It is critical to distinguish among different types and etiologies of TLE when predicting outcome after surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Route Learning Impairment in Temporal Lobe Epilepsy

PubMed Central

Bell, Brian D.

2012-01-01

Memory impairment on neuropsychological tests is relatively common in temporal lobe epilepsy (TLE) patients. But memory rarely has been evaluated in more naturalistic settings. This study assessed TLE (n = 19) and control (n = 32) groups on a real-world route learning (RL) test. Compared to the controls, the TLE group committed significantly more total errors across the three RL test trials. RL errors correlated significantly with standardized auditory and visual memory and visual-perceptual test scores in the TLE group. In the TLE subset for whom hippocampal data were available (n = 14), RL errors also correlated significantly with left hippocampal volume. This is one of the first studies to demonstrate real-world memory impairment in TLE patients and its association with both mesial temporal lobe integrity and standardized memory test performance. The results support the ecological validity of clinical neuropsychological assessment. PMID:23041173

Epilepsy increases vulnerability of long-term face recognition to proactive interference.

PubMed

Bengner, T; Malina, T; Lindenau, M; Voges, B; Goebell, E; Stodieck, S

2006-02-01

Proactive interference (PI) decreases short- and long-term memory in healthy subjects. Neurological patients exhibit a heightened PI effect on short-term memory. It is, however, not known if PI affects long-term memory in neurological patients. We analyzed whether epilepsy heightens the negative effect of PI on long-term face memory. PI was induced by a list of 20 faces learned 24 hours prior to a target list of 20 faces. We tested immediate and 24-hour recognition for both lists. Twelve healthy controls and 42 patients with generalized epilepsy or temporal lobe epilepsy (TLE) were studied. PI led to a decrease in 24-hour recognition in patients with generalized epilepsy and TLE but not in controls. Thus, PI may cause long-term memory disturbances in epilepsy patients. PI was also associated with decreased short-term memory, but only in right TLE. This confirms the dominant role of the right temporal lobe in short-term face memory.

Current psychiatric disorders in patients with epilepsy are predicted by maltreatment experiences during childhood.

PubMed

Labudda, Kirsten; Illies, Dominik; Herzig, Cornelia; Schröder, Katharina; Bien, Christian G; Neuner, Frank

2017-09-01

Childhood maltreatment has been shown to be a risk factor for the development of psychiatric disorders. Although the prevalence of psychiatric disorders is high in epilepsy patients, it is unknown if childhood maltreatment experiences are elevated compared to the normal population and if early maltreatment is a risk factor for current psychiatric comorbidities in epilepsy patients. This is the main purpose of this study. Structured interviews were used to assess current Axis I diagnoses in 120 epilepsy patients from a tertiary Epilepsy Center (34 TLE patients, 86 non-TLE patients). Childhood maltreatment in the family and peer victimization were assessed with validated questionnaires. Patients' maltreatment scores were compared with those of a representative matched control group. Logistic regression analysis was conducted to assess the potential impact of childhood maltreatment on current psychiatric comorbidity in epilepsy patients. Compared to a matched control group, epilepsy patients had higher emotional and sexual maltreatment scores. Patients with a current psychiatric diagnosis reported more family and peer maltreatment than patients without a psychiatric disorder. Family maltreatment scores predicted the likelihood of a current psychiatric disorder. TLE patients did not differ from non-TLE patients according to maltreatment experiences and rates of current psychiatric disorders. Our findings suggest that in epilepsy patients emotional and sexual childhood maltreatment is experienced more often than in the normal population and that early maltreatment is a general risk factor for psychiatric comorbidities in this group. Copyright © 2017 Elsevier B.V. All rights reserved.

Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy

PubMed Central

Loi, Richard Q.; Leyden, Kelly M.; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J.; Paul, Brianna M.; Dale, Anders M.; White, Nathan S.; McDonald, Carrie R.

2016-01-01

Objective Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI’s ability to separate intra-axonal diffusion (i.e., neurite density; ND) from diffusion associated with extra-axonal factors (e.g., inflammation; crossing fibers). Methods RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic hindered (IH) and free (IF) water, and crossing fibers (CF) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Results Reductions in FA were seen primarily in frontotemporal white matter in TLE and were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. Significance RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy. PMID:27735051

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality.

PubMed

Bartolini, Luca; Whitehead, Matthew T; Ho, Cheng-Ying; Sepeta, Leigh N; Oluigbo, Chima O; Havens, Kathryn; Freilich, Emily R; Schreiber, John M; Gaillard, William D

2017-01-01

To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD). We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies. Rates of pathology subtypes differed between TLE and ETLE (χ 2 (3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ 2 (1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ 2 (1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ 2 (6) = 13.07, p = 0.042). Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

A functional magnetic resonance imaging investigation of theory of mind impairments in patients with temporal lobe epilepsy.

PubMed

Hennion, Sophie; Delbeuck, Xavier; Koelkebeck, Katja; Brion, Marine; Tyvaert, Louise; Plomhause, Lucie; Derambure, Philippe; Lopes, Renaud; Szurhaj, William

2016-12-01

Although patients with mesial temporal lobe epilepsy (mTLE) are known to have theory of mind (ToM) impairments, the latter's neural functional bases have yet to be explored. We used functional magnetic resonance imaging (fMRI) to gain insights into the neural dysfunction associated with ToM impairments in patients with mTLE. Twenty-five patients (12 and 13 with right and left mTLE, respectively) and 25 healthy controls performed the "animated shapes" task during fMRI. This complex ToM task requires both explicit reasoning about mental states and implicit processing of information on biological motion and action. The animated shapes evoke both ToM and non-ToM interaction perception, and the corresponding neural activation patterns were compared. Behavioral performance (i.e. categorization of the interactions) was also recorded. Relative to healthy controls, both patients with right and left mTLE were impaired in categorizing ToM interactions. The fMRI results showed that both patients with right and left mTLE had less intense neural activation (relative to controls) in regions involved in the implicit component of ToM processes (i.e. the fusiform gyrus in patients with right mTLE and the supplementary motor area in patients with left mTLE). In patients with right mTLE, we also observed more intense activation (relative to controls) in regions involved in the explicit component of ToM processes (i.e. the dorsal medial prefrontal cortex); age at onset of epilepsy also mediated activation in regions involved in the explicit component (i.e. the ventral medial prefrontal cortex and the temporoparietal junction). Patients with left mTLE displayed greater activation of the contralateral mesial regions (relative to controls); we speculate that this may correspond to the deployment of a compensatory mechanism. This study provides insights into the disturbances of the implicit/explicit ToM neural network in patients with mTLE. These impairments in the ToM neural network depend on clinical characteristics, such as the laterality (right or left mTLE) and the age at onset of epilepsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetics of Temporal Lobe Epilepsy: A Review

PubMed Central

Salzmann, Annick; Malafosse, Alain

2012-01-01

Temporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex disorder. To understand its genetic component, numerous linkage analyses of familial forms and association studies of cases versus controls have been conducted since the middle of the nineties. The present paper lists genetic findings for TLE from the initial segregation analysis to the most recent results published in May 2011. To date, no genes have been clearly related to TLE despite many efforts to do so. However, it is vital to continue replication studies and collaborative attempts to find significant results and thus determine which gene variant combination plays a definitive role in the aetiology of TLE. PMID:22957248

Sex differences in verbal and nonverbal learning before and after temporal lobe epilepsy surgery.

PubMed

Berger, Justus; Oltmanns, Frank; Holtkamp, Martin; Bengner, Thomas

2017-01-01

Women outperform men in a host of episodic memory tasks, yet the neuroanatomical basis for this effect is unclear. It has been suggested that the anterior temporal lobe might be especially relevant for sex differences in memory. In the current study, we investigated whether temporal lobe epilepsy (TLE) has an influence on sex effects in learning and memory and whether women and men with TLE differ in their risk for memory deficits after epilepsy surgery. 177 patients (53 women and 41 men with left TLE, 42 women and 41 men with right TLE) were neuropsychologically tested before and one year after temporal lobe resection. We found that women with TLE had better verbal, but not figural, memory than men with TLE. The female advantage in verbal memory was not affected by temporal lobe resection. The same pattern of results was found in a more homogeneous subsample of 84 patients with only hippocampal sclerosis who were seizure-free after surgery. Our findings challenge the concept that the anterior temporal lobe plays a central role in the verbal memory advantage for women. Copyright © 2016 Elsevier Inc. All rights reserved.

Unique and shared validity of the "Wechsler logical memory test", the "California verbal learning test", and the "verbal learning and memory test" in patients with epilepsy.

PubMed

Helmstaedter, Christoph; Wietzke, Jennifer; Lutz, Martin T

2009-12-01

This study was set-up to evaluate the construct validity of three verbal memory tests in epilepsy patients. Sixty-one consecutively evaluated patients with temporal lobe epilepsy (TLE) or extra-temporal epilepsy (E-TLE) underwent testing with the verbal learning and memory test (VLMT, the German equivalent of the Rey auditory verbal learning test, RAVLT); the California verbal learning test (CVLT); the logical memory and digit span subtests of the Wechsler memory scale, revised (WMS-R); and testing of intelligence, attention, speech and executive functions. Factor analysis of the memory tests resulted in test-specific rather than test over-spanning factors. Parameters of the CVLT and WMS-R, and to a much lesser degree of the VLMT, were highly correlated with attention, language function and vocabulary. Delayed recall measures of logical memory and the VLMT differentiated TLE from E-TLE. Learning and memory scores off all three tests differentiated mesial temporal sclerosis from other pathologies. A lateralization of the epilepsy was possible only for a subsample of 15 patients with mesial TLE. Although the three tests provide overlapping indicators for a temporal lobe epilepsy or a mesial pathology, they can hardly be taken in exchange. The tests have different demands on semantic processing and memory organization, and they appear differentially sensitive to performance in non-memory domains. The tests capability to lateralize appears to be poor. The findings encourage the further discussion of the dependency of memory outcomes on test selection.

Brain morphological and microstructural features in cryptogenic late-onset temporal lobe epilepsy: a structural and diffusion MRI study.

PubMed

Sone, Daichi; Sato, Noriko; Kimura, Yukio; Watanabe, Yutaka; Okazaki, Mitsutoshi; Matsuda, Hiroshi

2018-06-01

Although epilepsy in the elderly has attracted attention recently, there are few systematic studies of neuroimaging in such patients. In this study, we used structural MRI and diffusion tensor imaging (DTI) to investigate the morphological and microstructural features of the brain in late-onset temporal lobe epilepsy (TLE). We recruited patients with TLE and an age of onset > 50 years (late-TLE group) and age- and sex-matched healthy volunteers (control group). 3-Tesla MRI scans, including 3D T1-weighted images and 15-direction DTI, showed normal findings on visual assessment in both groups. We used Statistical Parametric Mapping 12 (SPM12) for gray and white matter structural normalization and comparison and used Tract-Based Spatial Statistics (TBSS) for fractional anisotropy and mean diffusivity comparisons of DTI. In both methods, p < 0.05 (family-wise error) was considered statistically significant. In total, 30 patients with late-onset TLE (mean ± SD age, 66.8 ± 8.4; mean ± SD age of onset, 63.0 ± 7.6 years) and 40 healthy controls (mean ± SD age, 66.6 ± 8.5 years) were enrolled. The late-onset TLE group showed significant gray matter volume increases in the bilateral amygdala and anterior hippocampus and significantly reduced mean diffusivity in the left temporofrontal lobe, internal capsule, and brainstem. No significant changes were evident in white matter volume or fractional anisotropy. Our findings may reflect some characteristics or mechanisms of cryptogenic TLE in the elderly, such as inflammatory processes.

Differences in graph theory functional connectivity in left and right temporal lobe epilepsy.

PubMed

Chiang, Sharon; Stern, John M; Engel, Jerome; Levin, Harvey S; Haneef, Zulfi

2014-12-01

To investigate lateralized differences in limbic system functional connectivity between left and right temporal lobe epilepsy (TLE) using graph theory. Interictal resting state fMRI was performed in 14 left TLE patients, 11 right TLE patients, and 12 controls. Graph theory analysis of 10 bilateral limbic regions of interest was conducted. Changes in edgewise functional connectivity, network topology, and regional topology were quantified, and then left and right TLE were compared. Limbic edgewise functional connectivity was predominantly reduced in both left and right TLE. More regional connections were reduced in right TLE, most prominently involving reduced interhemispheric connectivity between the bilateral insula and bilateral hippocampi. A smaller number of limbic connections were increased in TLE, more so in left than in right TLE. Topologically, the most pronounced change was a reduction in average network betweenness centrality and concurrent increase in left hippocampal betweenness centrality in right TLE. In contrast, left TLE exhibited a weak trend toward increased right hippocampal betweenness centrality, with no change in average network betweenness centrality. Limbic functional connectivity is predominantly reduced in both left and right TLE, with more pronounced reductions in right TLE. In contrast, left TLE exhibits both edgewise and topological changes that suggest a tendency toward reorganization. Network changes in TLE and lateralized differences thereof may have important diagnostic and prognostic implications. Published by Elsevier B.V.

Dream recall frequency and content in patients with temporal lobe epilepsy.

PubMed

Bentes, Carla; Costa, João; Peralta, Rita; Pires, Joana; Sousa, Paula; Paiva, Teresa

2011-11-01

To evaluate morning dream recall frequency and content in patients with temporal lobe epilepsy (TLE). Fifty-two patients with pharmacoresistant TLE submitted to a written dream diary during five consecutive days and continuous video-electroencephalographic (video-EEG) monitoring. A matched control group of 41 healthy subjects completed the same diary at home. The number of recalled dreams (including long dreams) and nonrecalled dream mentation were collected, and the Dream Recall Rate (DRR) was calculated. Hall and Van de Castle dream content analysis was performed. Greater than 70% of patients with TLE (37 of 52) recall their dreams, but DRR rate in these patients is lower than in controls (p ≤ 0.001). Dream recall does not appear to be influenced by the presence of neuropsychological deficits nor seizure frequency. In dreams descriptions, TLE patients (vs. controls) have a higher percentage of familiarity in settings and fewer dreams with at least one success. Onirical activity of patients with TLE is different from that of healthy subjects. Our results support the role of mesial and neocortical temporal structures in dream experience. The selective activation of dysfunctional mesial structures may be responsible for some of the observed variability. However, dream content changes can also mirror social and psychological comorbidities of patients with epilepsy. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

PubMed

Sidhu, Meneka K; Thompson, Pamela J; Wandschneider, Britta; Foulkes, Alexandra; de Tisi, Jane; Stretton, Jason; Perona, Marina; Thom, Maria; Bonelli, Silvia B; Burdett, Jane; Williams, Elaine; Duncan, John S; Matarin, Mar

2018-06-27

Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE. © 2018 John Wiley & Sons Ltd.

Preoperative assessment of confrontation naming ability and interictal paraphasia production in unilateral temporal lobe epilepsy.

PubMed

Schefft, Bruce K; Testa, S Marc; Dulay, Mario F; Privitera, Michael D; Yeh, Hwa-Shain

2003-04-01

The present study examined the diagnostic utility of confrontation naming tasks and phonemic paraphasia production in lateralizing the epileptogenic region in patients with temporal lobe epilepsy (TLE). Further, the role of intelligence in moderating the diagnostic utility of confrontation naming tasks was assessed. Eighty patients with medically intractable complex partial seizures (40 left TLE, 40 right TLE) received the Boston Naming Test (BNT) and the Visual Naming subtest (VNT) of the Multilingual Aphasia Examination. The BNT was diagnostically more sensitive than the VNT in identifying left TLE (77.5% vs 17.5%, respectively). The utility of BNT performance and paraphasias was maximal in patients with Full Scale IQs >or=90 who were 6.8 times more likely to have left TLE than patients without paraphasias. Preoperative assessment of confrontation naming ability and phonemic paraphasia production using the BNT provided diagnostically useful information in lateralizing the epileptogenic region in left TLE.

Neocortical Temporal Lobe Epilepsy

PubMed Central

Bercovici, Eduard; Kumar, Balagobal Santosh; Mirsattari, Seyed M.

2012-01-01

Complex partial seizures (CPSs) can present with various semiologies, while mesial temporal lobe epilepsy (mTLE) is a well-recognized cause of CPS, neocortical temporal lobe epilepsy (nTLE) albeit being less common is increasingly recognized as separate disease entity. Differentiating the two remains a challenge for epileptologists as many symptoms overlap due to reciprocal connections between the neocortical and the mesial temporal regions. Various studies have attempted to correctly localize the seizure focus in nTLE as patients with this disorder may benefit from surgery. While earlier work predicted poor outcomes in this population, recent work challenges those ideas yielding good outcomes in part due to better localization using improved anatomical and functional techniques. This paper provides a comprehensive review of the diagnostic workup, particularly the application of recent advances in electroencephalography and functional brain imaging, in neocortical temporal lobe epilepsy. PMID:22953057

Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium.

PubMed

Hermann, B P; Trenerry, M R; Colligan, R C

1996-07-01

We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.

Memory, Metamemory and Their Dissociation in Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Howard, Charlotte E.; Andres, Pilar; Broks, Paul; Noad, Rupert; Sadler, Martin; Coker, Debbie; Mazzoni, Giuliana

2010-01-01

Patients with temporal-lobe epilepsy (TLE) present with memory difficulties. The aim of the current study was to determine to what extent these difficulties could be related to a metamemory impairment. Fifteen patients with TLE and 15 matched healthy controls carried out a paired-associates learning task. Memory recall was measured at intervals of…

Disrupted Structural and Functional Networks and Their Correlation with Alertness in Right Temporal Lobe Epilepsy: A Graph Theory Study.

PubMed

Jiang, Wenyu; Li, Jianping; Chen, Xuemei; Ye, Wei; Zheng, Jinou

2017-01-01

Previous studies have shown that temporal lobe epilepsy (TLE) involves abnormal structural or functional connectivity in specific brain areas. However, limited comprehensive studies have been conducted on TLE associated changes in the topological organization of structural and functional networks. Additionally, epilepsy is associated with impairment in alertness, a fundamental component of attention. In this study, structural networks were constructed using diffusion tensor imaging tractography, and functional networks were obtained from resting-state functional MRI temporal series correlations in 20 right temporal lobe epilepsy (rTLE) patients and 19 healthy controls. Global network properties were computed by graph theoretical analysis, and correlations were assessed between global network properties and alertness. The results from these analyses showed that rTLE patients exhibit abnormal small-world attributes in structural and functional networks. Structural networks shifted toward more regular attributes, but functional networks trended toward more random attributes. After controlling for the influence of the disease duration, negative correlations were found between alertness, small-worldness, and the cluster coefficient. However, alertness did not correlate with either the characteristic path length or global efficiency in rTLE patients. Our findings show that disruptions of the topological construction of brain structural and functional networks as well as small-world property bias are associated with deficits in alertness in rTLE patients. These data suggest that reorganization of brain networks develops as a mechanism to compensate for altered structural and functional brain function during disease progression.

How do cognition, emotion, and epileptogenesis meet? A study of emotional cognitive bias in temporal lobe epilepsy.

PubMed

Lanteaume, Laura; Bartolomei, Fabrice; Bastien-Toniazzo, Mireille

2009-06-01

Emotional distress is one of the most frequently reported seizure precipitants in epilepsy, but little is known about its causes and processes. Interestingly, it is now accepted that emotional distress, such as anxiety, may be accompanied by evolutionary adaptation, or abnormal attentional vigilance toward threatening stimuli. The goal of this research was to study the link between emotional seizure precipitants and pathological attention-related biases toward threat in temporal lobe epilepsy (TLE). To this aim, patients were asked to report the extent to which seizures were elicited or not by emotional precipitants, allowing distinction of two groups: "Emo-TLE" group and "Other-TLE" group. Attentional biases were investigated by comparing patients' emotional Stroop and dot detection paradigms with those of healthy individuals (control group). We found that the Emo-TLE group was characterized by attentional bias toward threatening stimuli compared with neutral stimuli and compared with the other two groups. We thus hypothesize that attentional biases related to threat in patients with TLE may sustain emotional vulnerability and seizure occurrence.

Disrupted topological properties of brain white matter networks in left temporal lobe epilepsy: a diffusion tensor imaging study.

PubMed

Xu, Y; Qiu, S; Wang, J; Liu, Z; Zhang, R; Li, S; Cheng, L; Liu, Z; Wang, W; Huang, R

2014-10-24

Mesial temporal lobe epilepsy (mTLE) is the most common drug-refractory focal epilepsy in adults. Although previous functional and morphological studies have revealed abnormalities in the brain networks of mTLE, the topological organization of the brain white matter (WM) networks in mTLE patients is still ambiguous. In this study, we constructed brain WM networks for 14 left mTLE patients and 22 age- and gender-matched normal controls using diffusion tensor tractography and estimated the alterations of network properties in the mTLE brain networks using graph theoretical analysis. We found that networks for both the mTLE patients and the controls exhibited prominent small-world properties, suggesting a balanced topology of integration and segregation. However, the brain WM networks of mTLE patients showed a significant increased characteristic path length but significant decreased global efficiency, which indicate a disruption in the organization of the brain WM networks in mTLE patients. Moreover, we found significant between-group differences in the nodal properties in several brain regions, such as the left superior temporal gyrus, left hippocampus, the right occipital and right temporal cortices. The robustness analysis showed that the results were likely to be consistent for the networks constructed with different definitions of node and edge weight. Taken together, our findings may suggest an adverse effect of epileptic seizures on the organization of large-scale brain WM networks in mTLE patients. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Stigma and quality of life at long-term follow-up after surgery for epilepsy in Uganda.

PubMed

Fletcher, Anita; Sims-Williams, Helen; Wabulya, Angela; Boling, Warren

2015-11-01

Epilepsy is a worldwide health problem with a 10-fold greater prevalence in the developing world. Commonly, the seizure focus is in the temporal lobe, and seizures in about 30% of people with epilepsy are intractable to medication. For these individuals, surgery for intractable temporal lobe epilepsy (iTLE) is more effective than medication alone and may be the only option for cure. Intractable temporal lobe epilepsy is associated with elevated morbidity and mortality, reduced quality of life (QOL), and associated stigma particularly occurring in the developing world. Individuals with intractable epilepsy who participated in an earlier Uganda pilot study were selected for the current study based on their undergoing previous surgery for iTLE or having comparable seizure type who did not have surgery. At long-term follow-up, 10 who underwent surgery for iTLE in addition to 9 patients with focal dyscognitive type epilepsy who did not have surgery were evaluated in the current study. Tests were administered to look at various outcome parameters: seizure severity, QOL, stigma, and self-esteem. Stigma and self-esteem were additionally evaluated in the parent/caregiver. Seventy-percent of surgical resection patients were seizure-free at 8 years postsurgery. The QOLIE-31 scores were higher in surgical patients. Child/patient and parent/proxy surveys identified lower stigma in seizure-free patients. The results suggest that surgery for iTLE is an effective treatment for epilepsy in the developing world and provides an opportunity to reduce stigma and improve QOL. Copyright © 2015 Elsevier Inc. All rights reserved.

A componential analysis of proverb interpretation in patients with frontal lobe epilepsy and temporal lobe epilepsy: relationships with disease-related factors.

PubMed

McDonald, Carrie R; Delis, Dean C; Kramer, Joel H; Tecoma, Evelyn S; Iragui, Vicente J

2008-05-01

The ability to interpret nonliteral, metaphoric language was explored in patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), and matched control participants, to determine (1) if patients with FLE were impaired in their interpretations relative to those with TLE and controls, and (2) if disease-related variables (e.g., age of seizure onset) predicted performances in either patient group. A total of 22 patients with FLE, 20 patients with TLE, and 23 controls were administered a test of proverb interpretation to assess their ability to grasp the abstract meaning of nonliteral language. Participants were presented with a series of proverbs and asked to provide an oral interpretation of each. Responses to each proverb were scored according to their accuracy and level of abstractness. Patients with FLE, but not TLE, were impaired relative to controls in their overall interpretation of proverbs. However, a subgroup analysis revealed that only patients with left FLE showed impaired interpretation accuracy relative to the other groups, whereas patients with both left FLE and left TLE showed impaired abstraction. Patients with FLE were also impaired when they were asked to select the best interpretation of the proverb from response alternatives. In patients with FLE, only a left-sided seizure focus was associated with poorer performance. In patients with TLE, both an early age of onset and a left-sided seizure focus predicted poorer performance. Overall, FLE patients exhibit greater impairment than TLE patients in interpreting proverbs. However, the nature and disease-specific correlates of impaired performances in proverb interpretation differ between the groups.

A COMPONENTIAL ANALYSIS OF PROVERB INTERPRETATION IN PATIENTS WITH FRONTAL LOBE EPILEPSY AND TEMPORAL LOBE EPILEPSY: RELATIONSHIPS WITH DISEASE-RELATED FACTORS

PubMed Central

McDonald, Carrie R.; Delis, Dean C.; Kramer, Joel H.; Tecoma, Evelyn S.; Iragui, Vicente J.

2017-01-01

The ability to interpret nonliteral, metaphoric language was explored in patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), and matched control participants, to determine (1) if patients with FLE were impaired in their interpretations relative to those with TLE and controls, and (2) if disease-related variables (e.g., age of seizure onset) predicted performances in either patient group. A total of 22 patients with FLE, 20 patients with TLE, and 23 controls were administered a test of proverb interpretation to assess their ability to grasp the abstract meaning of nonliteral language. Participants were presented with a series of proverbs and asked to provide an oral interpretation of each. Responses to each proverb were scored according to their accuracy and level of abstractness. Patients with FLE, but not TLE, were impaired relative to controls in their overall interpretation of proverbs. However, a subgroup analysis revealed that only patients with left FLE showed impaired interpretation accuracy relative to the other groups, whereas patients with both left FLE and left TLE showed impaired abstraction. Patients with FLE were also impaired when they were asked to select the best interpretation of the proverb from response alternatives. In patients with FLE, only a left-sided seizure focus was associated with poorer performance. In patients with TLE, both an early age of onset and a left-sided seizure focus predicted poorer performance. Overall, FLE patients exhibit greater impairment than TLE patients in interpreting proverbs. However, the nature and disease-specific correlates of impaired performances in proverb interpretation differ between the groups. PMID:17853125

The patient had a normal magnetic resonance imaging and temporal lobe epilepsy secondary to a porencephalic cyst but showed structural lesions (hippocampal sclerosis)☆

PubMed Central

Matsubara, Teppei; Ayuzawa, Satoshi; Aoki, Tsukasa; Fujiomto, Ayataka; Osuka, Satoru; Matsumura, Akira

2013-01-01

Patients with a porencephalic cyst frequently develop intractable temporal lobe epilepsy (TLE). We report a surgically-treated male patient with intractable mesial TLE (mTLE) secondary to a porencephalic cyst. Although magnetic resonance imaging showed no hippocampal abnormalities, long-term video-electrocorticography revealed seizure onset discharges in the hippocampus. Temporal lobectomy brought an end to the patient's seizures. Hippocampal sclerosis was histopathologically confirmed (dual pathology). Careful evaluation of hippocampal epileptogenicity is required, and temporal lobectomy, which is less invasive than hemispherectomy, can be a treatment of choice for patients with mTLE secondary to a porencephalic cyst. PMID:25667851

Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

PubMed Central

Janz, Philipp; Schwaderlapp, Niels; Heining, Katharina; Häussler, Ute; Korvink, Jan G; von Elverfeldt, Dominik; Hennig, Jürgen; Egert, Ulrich

2017-01-01

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. DOI: http://dx.doi.org/10.7554/eLife.25742.001 PMID:28746029

Glycine Transporter 1 is a Target for the Treatment of Epilepsy

PubMed Central

Shen, Hai-Ying; van Vliet, Erwin; Bright, Kerry-Ann; Hanthorn, Marissa; Lytle, Nikki; Gorter, Jan; Aronica, Eleonora; Boison, Detlev

2015-01-01

Glycine is the major inhibitory neurotransmitter in brainstem and spinal cord, whereas in hippocampus glycine exerts dual modulatory roles on strychnine-sensitive glycine receptors and on the strychnine-insensitive glycineB site of the N-methyl-D-aspartate receptor (NMDAR). In hippocampus, the synaptic availability of glycine is largely under control of glycine transporter 1 (GlyT1). Since epilepsy is a disorder of disrupted network homeostasis affecting the equilibrium of various neurotransmitters and neuromodulators, we hypothesized that changes in hippocampal GlyT1 expression and resulting disruption of glycine homeostasis might be implicated in the pathophysiology of epilepsy. Using two different rodent models of temporal lobe epilepsy (TLE) – the intrahippocampal kainic acid model of TLE in mice, and the rat model of tetanic stimulation-induced TLE – we first demonstrated robust overexpression of GlyT1 in the hippocampal formation, suggesting dysfunctional glycine signaling in epilepsy. Overexpression of GlyT1 in the hippocampal formation was corroborated in human TLE samples by quantitative real time PCR. In support of a role of dysfunctional glycine signaling in the pathophysiology of epilepsy, both the genetic deletion of GlyT1 in hippocampus and the GlyT1 inhibitor LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109. We conclude that GlyT1 overexpression in the epileptic brain constitutes a new target for therapeutic intervention, and that GlyT1 inhibitors constitute a new class of antiictogenic drugs. These findings are of translational value since GlyT1 inhibitors are already in clinical development to treat cognitive symptoms in schizophrenia. PMID:26302655

Decision making under ambiguity and under risk in mesial temporal lobe epilepsy.

PubMed

Delazer, Margarete; Zamarian, Laura; Bonatti, Elisabeth; Kuchukhidze, Giorgi; Koppelstätter, Florian; Bodner, Thomas; Benke, Thomas; Trinka, Eugen

2010-01-01

Decision making is essential in everyday life. Though the importance of the mesial temporal lobe in emotional processing and feedback learning is generally recognized, decision making in mesial temporal lobe epilepsy (mTLE) is almost unexplored so far. Twenty-eight consecutive epilepsy patients with drug resistant mTLE and fifty healthy controls performed decision tasks under initial ambiguity (participants have to learn by feedback to make advantageous decisions) and under risk (advantageous choices may be made by estimating risks and by rational strategies). A subgroup analysis compared the performance of patients affected by MRI-verified abnormalities of the hippocampus or amygdala. The effect of lesion side was also assessed. In decision under ambiguity, mTLE patients showed marked deficits and did not improve over the task. Patients with hippocampus abnormality and patients with amygdala abnormality showed comparable deficits. No difference was found between right and left TLE groups. In decision under risk, mTLE patients performed at the same level as controls. Results suggest that mTLE patients have difficulties in learning from feedback and in making decisions in uncertain, ambiguous situations. By contrast, they are able to make advantageous decisions when full information is given and risks, possible gains and losses are exactly defined.

Differential neuropsychological test sensitivity to left temporal lobe epilepsy.

PubMed

Loring, David W; Strauss, Esther; Hermann, Bruce P; Barr, William B; Perrine, Kenneth; Trenerry, Max R; Chelune, Gordon; Westerveld, Michael; Lee, Gregory P; Meador, Kimford J; Bowden, Stephen C

2008-05-01

We examined the sensitivity of the Rey Auditory Verbal Learning Test (AVLT), California Verbal Learning Test (CVLT), Boston Naming Test (BNT), and Multilingual Aphasia Examination Visual Naming subtest (MAE VN) to lateralized temporal lobe epilepsy (TLE) in patients who subsequently underwent anterior temporal lobectomy. For the AVLT (n = 189), left TLE patients performed more poorly than their right TLE counterparts [left TLE = 42.9 (10.6), right TLE = 47.7 (9.9); p < .002 (Cohen's d = .47)]. Although statistically significant, the CVLT group difference (n = 212) was of a smaller magnitude [left LTE = 40.7 (11.1), right TLE = 43.8 (9.9); (p < .03, Cohen's d = .29)] than the AVLT. Group differences were also present for both measures of confrontation naming ability [BNT: left LTE = 43.1 (8.9), right TLE = 48.1 (8.9); p < .001 (Cohen's d = .56); MAE VN: left TLE = 42.2, right TLE = 45.6, p = .02 (Cohen's d = .36)]. When these data were modeled in independent logistic regression analyses, the AVLT and BNT both significantly predicted side of seizure focus, although the positive likelihood ratios were modest. In the subset of 108 patients receiving both BNT and AVLT, the AVLT was the only significant predictor of seizure laterality, suggesting individual patient variability regarding whether naming or memory testing may be more sensitive to lateralized TLE.

Verbal Dominant Memory Impairment and Low Risk for Post-operative Memory Worsening in Both Left and Right Temporal Lobe Epilepsy Associated with Hippocampal Sclerosis.

PubMed

Khalil, Amr Farid; Iwasaki, Masaki; Nishio, Yoshiyuki; Jin, Kazutaka; Nakasato, Nobukazu; Tominaga, Teiji

2016-11-15

Post-operative memory changes after temporal lobe surgery have been established mainly by group analysis of cognitive outcome. This study investigated individual patient-based memory outcome in surgically-treated patients with mesial temporal lobe epilepsy (TLE). This study included 84 consecutive patients with intractable TLE caused by unilateral hippocampal sclerosis (HS) who underwent epilepsy surgery (47 females, 41 left [Lt] TLE). Memory functions were evaluated with the Wechsler Memory Scale-Revised before and at 1 year after surgery. Pre-operative memory function was classified into three patterns: verbal dominant memory impairment (Verb-D), visual dominant impairment (Vis-D), and no material-specific impairment. Post-operative changes in verbal and visual memory indices were classified into meaningful improvement, worsening, or no significant changes. Pre-operative patterns and post-operative changes in verbal and visual memory function were compared between the Lt and right (Rt) TLE groups. Pre-operatively, Verb-D was the most common type of impairment in both the Lt and Rt TLE groups (65.9 and 48.8%), and verbal memory indices were lower than visual memory indices, especially in the Lt compared with Rt TLE group. Vis-D was observed only in 11.6% of Rt and 7.3% of Lt TLE patients. Post-operatively, meaningful improvement of memory indices was observed in 23.3-36.6% of the patients, and the memory improvement was equivalent between Lt and Rt TLE groups and between verbal and visual materials. In conclusion, Verb-D is most commonly observed in patients with both the Lt and Rt TLE associated with HS. Hippocampectomy can improve memory indices in such patients regardless of the side of surgery and the function impaired.

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

PubMed

Ormond, D Ryan; Clusmann, Hans; Sassen, Robert; Hoppe, Christian; Helmstaedter, Christoph; Schramm, Johannes; Grote, Alexander

2018-04-13

Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery. To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort. One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes. Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%). Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.

Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies.

PubMed

Malter, M P; Frisch, C; Zeitler, H; Surges, R; Urbach, H; Helmstaedter, C; Elger, C E; Bien, C G

2015-08-01

Temporal lobe epilepsy with antibodies (abs) against the glutamic acid decarboxylase 65 isoform (GAD-TLE) is known as an immune-mediated neurological syndrome. Here we evaluate the therapy response to various immunotherapies and epilepsy surgery in this syndrome. All patients with GAD-TLE and follow-up data and stored serum and CSF samples, identified and treated at the Bonn centre from 2002 to 2010, were studied retrospectively. Seizure freedom for ≥1 year and reduction of ≥50%, i.e. therapy response, were assessed. GAD-ab titres and neuropsychological performances were documented prior and after individual interventions. Thirteen patients with GAD-TLE were identified with the following seizure responses: corticosteroids (5 responders out of 11 treated patients); i.v. immunoglobulins (1/5), apheresis therapy (1/8); and natalizumab (1/1), selective amygdala-hippocampectomy (2/3). None of the patients achieved sustained seizure freedom apart from one patient. This patient was on antiepileptic drug treatment after discontinuation of immunotherapy. The seizure response to immunotherapies in patients with GAD-TLE was poor. Corticosteroids were the most effective regarding seizure response. Especially the poor effects of apheresis therapies support the idea that GAD-abs are not directly pathogenic. None of three patients was seizure-free after temporal lobe surgery suggesting that GAD-TLE patients respond worse than others to this type of intervention. Our results reflect the chronic course of the disease with low likelihood for patients with GAD-TLE to attain long-term seizure freedom. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Patterns of verbal learning and memory in children with intractable temporal lobe or frontal lobe epilepsy.

PubMed

Fuentes, Amanda; Smith, Mary Lou

2015-12-01

The objective of this study was to provide a better understanding of the verbal learning and memory (VLM) patterns that might differentiate children with frontal lobe epilepsy (FLE) from children with temporal lobe epilepsy (TLE) and to examine the impact of variables thought to influence outcomes (seizure laterality, age at seizure onset, age at assessment, epilepsy duration, number of antiepileptic drugs). Retrospective analyses were carried out for children with intractable unilateral TLE (n=100) and FLE (n=27) who completed standardized measures of VLM entailing lists of single words or lists of word pairs. Mean intelligent quotients and VLM scores on single words fell within the average range for both groups, whereas scores fell within the low average to borderline range on word pairs. No significant overall differences in VLM were found between the group with TLE and the group with FLE. Older age at assessment and older age at seizure onset were generally associated with better VLM in both groups but were related to better performance in a number of indices in the group with TLE and only fewer intrusions in the group with FLE. The VLM profiles of children with TLE and FLE are generally similar. Older age at assessment and older age at seizure onset have a favorable impact on both groups but are related to better encoding, retrieval, and monitoring processes for the group with TLE and improved memory monitoring (i.e., as indicated by fewer intrusions) in the group with FLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Unique and shared areas of cognitive function in children with intractable frontal or temporal lobe epilepsy.

PubMed

Law, Nicole; Widjaja, Elysa; Smith, Mary Lou

2018-03-01

Previous findings have been mixed in terms of identifying a distinct pattern of neuropsychological deficits in children with frontal lobe epilepsy (FLE) and in those with temporal lobe epilepsy (TLE). The current study investigated the neuropsychological similarities and differences across these two pediatric medically intractable localization-related epilepsies. Thirty-eight children with FLE, 20 children with TLE, and 40 healthy children (HC) participated in this study. A comprehensive battery of standardized tests assessed five neuropsychological domains including intelligence, language, memory, executive function, and motor function. A principal component analysis (PCA) was used to distill our neuropsychological measures into latent components to compare between groups. Principal component analysis extracted 5 latent components: executive function (F1), verbal semantics (F2), motor (F3), nonverbal cognition/impulsivity (F4), and verbal cognition/attention (F5). The group with FLE differed from the HC group on F1, F2, F4, and F5, and had worse performance than the group with TLE on F1; the group with TLE had lower performance relative to the HC group on F2. Our findings suggest that, in comparison with neurotypically developing children, children with medically intractable FLE have more widespread neuropsychological impairments than do children with TLE. The differences between the two patient groups were greatest for the factor score most clearly related to executive function. The results provide mixed support for the concept of specificity in neuropsychological dysfunction among different subtypes of localization-related medically intractable childhood epilepsies. Copyright © 2018 Elsevier Inc. All rights reserved.

Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

PubMed Central

Johnson, Michael R.; Rossetti, Tiziana; Speed, Doug; Srivastava, Prashant K.; Chadeau-Hyam, Marc; Hajji, Nabil; Dabrowska, Aleksandra; Rotival, Maxime; Razzaghi, Banafsheh; Kovac, Stjepana; Wanisch, Klaus; Grillo, Federico W.; Slaviero, Anna; Langley, Sarah R.; Shkura, Kirill; Roncon, Paolo; De, Tisham; Mattheisen, Manuel; Niehusmann, Pitt; O’Brien, Terence J.; Petrovski, Slave; von Lehe, Marec; Hoffmann, Per; Eriksson, Johan; Coffey, Alison J.; Cichon, Sven; Walker, Matthew; Simonato, Michele; Danis, Bénédicte; Mazzuferi, Manuela; Foerch, Patrik; Schoch, Susanne; De Paola, Vincenzo; Kaminski, Rafal M.; Cunliffe, Vincent T.; Becker, Albert J.; Petretto, Enrico

2015-01-01

Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a mouse model of TLE using 100 epileptic and 100 control hippocampi shows the proconvulsive module is preserved across-species, specific to the epileptic hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3), and demonstrate that SESN3 positively regulates the module in macrophages, microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms the regulation of the transcriptional module, and attenuates chemically induced behavioural seizures in vivo. PMID:25615886

Temporal lobe epilepsy surgery: what do patients want to know?

PubMed

Choi, Hyunmi; Pargeon, Kim; Bausell, Rebecca; Wong, John B; Mendiratta, Anil; Bakken, Suzanne

2011-11-01

Patients with pharmacoresistant temporal lobe epilepsy (TLE) contemplating brain surgery must make a complex treatment decision involving trade-offs. Patient decision aids, containing information on the risks and benefits of treatment interventions, increase patient knowledge and facilitate shared decision making between patients and physicians. We conducted five focus groups to describe the information patients need to make informed decisions about TLE surgery. Twenty patients who had undergone TLE surgery described the information used in their decision-making process, and evaluated the potential for a patient decision aid to assist other patients who are considering surgery. Thematic analysis revealed information needs that were both experiential (i.e., learning about other patients' experiences through testimonials) and factual (i.e., individualized statistical information). Patients also made suggestions on how this information should be delivered to patients. These data will accelerate the development of a patient decision aid designed to assist TLE patients in their decision making about epilepsy surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

[Study based on ICA of "dorsal attention network" in patients with temporal lobe epilepsy].

PubMed

Yang, Zhigen; Wang, Huinan; Zhang, Zhiqiang; Zhong, Yuan; Chen, Zhili; Lu, Guangming

2010-02-01

Many functional magnetic resonance imaging (fMRI) studies have revealed the deactivation phenomenon of default mode network in the patients with epilepsy; however, nearly not any of the reports has focused on the dorsal attention network of epilepsy. In this paper, independent component analysis (ICA) was used to isolate the dorsal attention network of 16 patients with temporal lobe epilepsy (TLE) and of 20 healthy normals; and a goodness-of-fit analysis was applied at the individual subject level to choose the interesting component. Intra-group analysis and inter-group analysis were performed. The results indicated that the dorsal attention network included bilateral intraparietal sulcus, middle frontal gyrus, human frontal eye field, posterior lobe of right cerebellum, etc. The TLE group showed decreased functional connectivity in most of the dorsal attention regions with the predominance in the bilateral intraparietal sulcus, middle frontal gyrus, and posterior lobe of right cerebellum. These data suggested that the intrinsic organization of the brain function might be disrupted in TLE. In addition, the decrease of goodness-of-fit scores suggests that activity in the dorsal attention network may ultimately prove a sensitive biomarker for TLE.

Multivariate pattern analysis reveals anatomical connectivity differences between the left and right mesial temporal lobe epilepsy.

PubMed

Fang, Peng; An, Jie; Zeng, Ling-Li; Shen, Hui; Chen, Fanglin; Wang, Wensheng; Qiu, Shijun; Hu, Dewen

2015-01-01

Previous studies have demonstrated differences of clinical signs and functional brain network organizations between the left and right mesial temporal lobe epilepsy (mTLE), but the anatomical connectivity differences underlying functional variance between the left and right mTLE remain uncharacterized. We examined 43 (22 left, 21 right) mTLE patients with hippocampal sclerosis and 39 healthy controls using diffusion tensor imaging. After the whole-brain anatomical networks were constructed for each subject, multivariate pattern analysis was applied to classify the left mTLE from the right mTLE and extract the anatomical connectivity differences between the left and right mTLE patients. The classification results reveal 93.0% accuracy for the left mTLE versus the right mTLE, 93.4% accuracy for the left mTLE versus controls and 90.0% accuracy for the right mTLE versus controls. Compared with the right mTLE, the left mTLE exhibited a different connectivity pattern in the cortical-limbic network and cerebellum. The majority of the most discriminating anatomical connections were located within or across the cortical-limbic network and cerebellum, thereby indicating that these disease-related anatomical network alterations may give rise to a portion of the complex of emotional and memory deficit between the left and right mTLE. Moreover, the orbitofrontal gyrus, cingulate cortex, hippocampus and parahippocampal gyrus, which exhibit high discriminative power in classification, may play critical roles in the pathophysiology of mTLE. The current study demonstrated that anatomical connectivity differences between the left mTLE and the right mTLE may have the potential to serve as a neuroimaging biomarker to guide personalized diagnosis of the left and right mTLE.

Accelerated long-term forgetting in resected and seizure-free temporal lobe epilepsy patients.

PubMed

Visser, M; Forn, C; Gómez-Ibáñez, A; Rosell-Negre, P; Villanueva, V; Ávila, C

2018-03-12

Episodic memory impairments caused by temporal lobe epilepsy (TLE) are well documented in the literature. Standard clinical episodic memory tests typically include a 30-min delayed recall test. However, in the past decade, it has become apparent that this standard test does not capture the full range of memory problems in TLE patients. Some patients perform well on a standard 30-min delayed recall test, but show Accelerated Long-term Forgetting (ALF) after 24 h. Although ALF has been investigated in patients with different types of epilepsy, current research on resected TLE patients is missing. In the present study, resected TLE patients were compared to a control group matched on initial learning. They showed normal performance on verbal recall after 30 min, but impairments became apparent after one week. Moreover, the significant interaction between participant group and memory test delay demonstrated that the patients indeed showed an acceleration in forgetting. Furthermore, ALF was present in both left and right resected TLE patients, which contradicts the presence of material-specific hemispheric differences in ALF. In addition, ALF was observed in seizure-free resected TLE patients, thereby demonstrating that this factor is not crucial for long-term memory deficits. The outcome shows that clinicians are likely to underestimate memory deficits in resected TLE patients and, therefore, advocates for the inclusion of ALF tests in standard clinical batteries for both pre- and post-surgery testing sessions. Copyright © 2018 Elsevier Ltd. All rights reserved.

[New developments in epileptogenesis and therapeutic perspectives].

PubMed

Lerche, H; Vezzani, A; Beck, H; Blümcke, I; Weber, Y; Elger, C

2011-08-01

Epileptogenesis describes the mechanisms of how epilepsies are generated. We have chosen four areas in which significant progress has been achieved in understanding epileptogenesis. Those are (1) inflammatory processes which play an increasingly important role for the generation of temporal lobe epilepsy with hippocampal sclerosis (TLE with HS), (2) disturbances of intrinsic properties of neuronal compartments, in particular acquired defects of ion channels of which those in dendrites are described here for TLE with HS, (3) epigenetic effects, which affect for example the methylation of promoters and secondarily can change the expression of specific genes in TLE with HS, and finally (4) the epileptogenesis of idiopathic epilepsies which are caused by inborn genetic alterations affecting mainly ion channels. Apart from aspects of basic research, we will describe clinical consequences and therapeutic perspectives.

Lesional Temporal Lobe Epilepsy: Beware the Deceitful "Panic Attack".

PubMed

Kulason, Kay O; Schneider, Julia R; Rahme, Ralph; Pramanik, Bidyut; Chong, Derek; Boockvar, John A

2018-03-01

Ganglioglioma is a rare, benign, intraaxial glioneuronal tumor but a relatively common cause of pharmacoresistant temporal lobe epilepsy (TLE). Given its often nonspecific neuropsychiatric manifestations and frequently negative electroencephalographic workup, TLE can be easily misdiagnosed as a psychiatric disorder, particularly panic attacks. We present a case of a 17-year-old boy who was found to have lesional TLE secondary to a left temporal ganglioglioma, 5 years after having been misdiagnosed with panic disorder and having undergone ineffective and unnecessary psychotherapy. He was successfully cured by surgery. Although a few similar cases of TLE masquerading as a panic disorder have been previously reported in the literature, this is the youngest and only pediatric patient described to date. This report underscores the challenges in making an accurate clinical diagnosis of TLE and the importance of timely brain imaging whenever an atypical or medically refractory panic disorder is encountered. Copyright © 2017 Elsevier Inc. All rights reserved.

Imaging structural and functional brain networks in temporal lobe epilepsy.

PubMed

Bernhardt, Boris C; Hong, Seokjun; Bernasconi, Andrea; Bernasconi, Neda

2013-10-01

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.

Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures

PubMed Central

Finegersh, Andrey; Avedissian, Christina; Shamim, Sadat; Dustin, Irene; Thompson, Paul M.; Theodore, William H.

2011-01-01

Summary Purpose Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score ≥14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression. PMID:21269286

Mapping the convergent temporal epileptic network in left and right temporal lobe epilepsy.

PubMed

Fang, Peng; An, Jie; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

2017-02-03

Left and right mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) exhibits similar functional and clinical dysfunctions, such as depressive mood and emotional dysregulation, implying that the left and right mTLE may share a common network substrate. However, the convergent anatomical network disruption between the left and right HS remains largely uncharacterized. This study aimed to investigate whether the left and right mTLE share a similar anatomical network. We examined 43 (22 left, 21 right) mTLE patients with HS and 39 healthy controls using diffusion tensor imaging. Machine learning approaches were applied to extract the abnormal anatomical connectivity patterns in both the left and right mTLE. The left and right mTLE showed that 28 discriminating connections were exactly the same when compared to the controls. The same 28 connections showed high discriminating power in comparisons of the left mTLE versus controls (91.7%) and the right mTLE versus controls (90.0%); however, these connections failed to discriminate the left from the right mTLE. These discriminating connections, which were diminished both in the left and right mTLE, were primarily located in the limbic-frontal network, partially agreeing with the limbic-frontal dysregulation model of depression. These findings suggest that left and right mTLE share a convergent circuit, which may account for the mood and emotional deficits in mTLE and may suggest the neuropathological mechanisms underlying the comorbidity of depression and mTLE. Copyright © 2016. Published by Elsevier B.V.

Temporal lobe epilepsy surgery in children versus adults: from etiologies to outcomes

PubMed Central

Lee, Yun-Jin

2013-01-01

Temporal lobe epilepsy (TLE) is the most common type of medically intractable epilepsy in adults and children, and mesial temporal sclerosis is the most common underlying cause of TLE. Unlike in the case of adults, TLE in infants and young children often has etiologies other than mesial temporal sclerosis, such as tumors, cortical dysplasia, trauma, and vascular malformations. Differences in seizure semiology have also been reported. Motor manifestations are prominent in infants and young children, but they become less obvious with increasing age. Further, automatisms tend to become increasingly complex with age. However, in childhood and especially in adolescence, the clinical manifestations are similar to those of the adult population. Selective amygdalohippocampectomy can lead to excellent postoperative seizure outcome in adults, but favorable results have been seen in children as well. Anterior temporal lobectomy may prove to be a more successful surgery than amygdalohippocampectomy in children with intractable TLE. The presence of a focal brain lesion on magnetic resonance imaging is one of the most reliable independent predictors of a good postoperative seizure outcome. Seizure-free status is the most important predictor of improved psychosocial outcome with advanced quality of life and a lower proportion of disability among adults and children. Since the brain is more plastic during infancy and early childhood, recovery is promoted. In contrast, long epilepsy duration is an important risk factor for surgically refractory seizures. Therefore, patients with medically intractable TLE should undergo surgery as early as possible. PMID:23908666

Individual hippocampal subfield assessment indicates that matrix macromolecules and gliosis are key elements for the increased T2 relaxation time seen in temporal lobe epilepsy.

PubMed

Peixoto-Santos, Jose Eduardo; Kandratavicius, Ludmyla; Velasco, Tonicarlo Rodrigues; Assirati, Joao Alberto; Carlotti, Carlos Gilberto; Scandiuzzi, Renata Caldo; Salmon, Carlos Ernesto Garrido; Santos, Antonio Carlos Dos; Leite, Joao Pereira

2017-01-01

Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE. Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG. Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus. Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes.

PubMed

Kreilkamp, B A K; Weber, B; Elkommos, S B; Richardson, M P; Keller, S S

2018-06-01

To investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique. We recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1-weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes. Patients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus-amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes. Our results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome. © 2018 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

Monocarboxylate transporters in temporal lobe epilepsy: roles of lactate and ketogenic diet.

PubMed

Lauritzen, Fredrik; Eid, Tore; Bergersen, Linda H

2015-01-01

Epilepsy is a serious neurological disorder that affects approximately 1 % of the general population, making it one of the most common disorders of the central nervous system. Furthermore, up to 40 % of all patients with epilepsy cannot control their seizures with current medications. More efficacious treatments for medication refractory epilepsy are therefore needed. A better understanding of the mechanisms that cause this disorder is likely to facilitate the discovery of such treatments. Impairment in cerebral energy metabolism has been proposed as a possible causative factor in the pathogenesis of temporal lobe epilepsy (TLE), which is one of the most common types of medication-refractory epilepsies in adults. In this review, we will discuss some of the current hypotheses regarding the possible causal relationship between brain energy metabolism and TLE. Emphasis will be placed on the role of energy substrates (lactate and ketone bodies) and their transporter molecules, particularly monocarboxylate transporters 1 and 2 (MCT1 and MCT2). We recently reported that the cellular distribution of MCT1 and MCT2 is perturbed in the hippocampus in patients with TLE. The changes may be an adaptive response aimed at keeping high levels of lactate in the epileptic tissue, which may serve to counteract epileptic activity by downregulating cAMP levels through the lactate receptor GPR81, newly discovered in hippocampus. We propose that the perturbation of MCTs may be further involved in the pathophysiology of TLE by influencing brain energy homeostasis, mitochondrial function, GABA-ergic and glutamatergic neurotransmission, and flux of lactate through the brain.

Dissociation of Short- and Long-Term Face Memory: Evidence from Long-Term Recency Effects in Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Bengner, T.; Malina, T.

2007-01-01

We tested whether memory deficits in temporal lobe epilepsy (TLE) are better described by a single- or dual-store memory model. To this aim, we analyzed the influence of TLE and proactive interference (PI) on immediate and 24-h long-term recency effects during face recognition in 16 healthy participants and 18 right and 21 left non-surgical TLE…

Differences in sleep architecture between left and right temporal lobe epilepsy.

PubMed

Nakamura, Miki; Jin, Kazutaka; Kato, Kazuhiro; Itabashi, Hisashi; Iwasaki, Masaki; Kakisaka, Yosuke; Nakasato, Nobukazu

2017-01-01

To investigate whether seizure lateralization affects sleep macrostructure in patients with left and right temporal lobe epilepsy (TLE), as rapid eye movement (REM) sleep is shorter in patients with right hemispheric cerebral infarction than with left. We retrospectively analyzed data from 16 patients with TLE (6 men and 10 women aged 34.9 ± 11.4 years) who underwent polysomnography as well as long-term video electroencephalography. Ten patients were diagnosed with left TLE and six patients with right TLE. Sleep stages and respiratory events were scored based on the American Academy of Sleep Medicine criteria. Sleep and respiratory parameters were compared between the patient groups. Percentage of REM stage sleep was significantly (p < 0.05) lower in patients with left TLE (median 8.8 %, interquartile range 5.5-13.8 %) than in patients with right TLE (median 17.0 %, interquartile range 14.1-18.3 %). The other parameters showed no significant differences. Shorter REM sleep in patients with left TLE sharply contrasts with the previous report of shorter REM sleep in patients with right cerebral infarction. Laterality of the irritative epileptic focus versus destructive lesion may have different effects on the sleep macrostructures.

Effect of Temporal Neocortical Pathology on Seizure Freeness in Adult Patients with Temporal Lobe Epilepsy.

PubMed

Kemerdere, Rahsan; Ahmedov, Merdin Lyutviev; Alizada, Orkhan; Yeni, Seher Naz; Oz, Buge; Tanriverdi, Taner

2018-05-23

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Focal cortical dysplasia is the most common dual pathology found in association with the hippocampal sclerosis. In this study, the effect of dual pathology on freedom from seizure was sought in patients with TLE. This study performed a retrospective analysis of patients with TLE who underwent surgery between 2010 and 2017. Histopathologic analysis was performed on patients with and without dual pathology in the temporal neocortex. Seizure outcomes were compared. A total of 54 patients with TLE were included. The rate of overall favorable seizure outcome was found to be 96.3%. In 53.7%, dual pathology was present in the temporal cortices in addition to the hippocampal sclerosis. Patients without dual pathology showed significantly greater freedom from seizure (P = 0.02). Patients without dual pathology had a significantly higher seizure-free rate after anterior temporal resection than patients with dual pathology. Resection of the temporal cortex in addition to mesial temporal structures seems to be reasonable for better seizure outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

Decrease of NAA with aging outside the seizure focus in mesial temporal lobe epilepsy--a proton-MRS study at 3 Tesla.

PubMed

Riederer, Franz; Bittsanský, Michal; Lehner-Baumgartner, Eva; Baumgartner, Christoph; Mlynárik, Vladimír; Gruber, Stephan; Moser, Ewald; Kaya, Marihan; Serles, Wolfgang

2007-11-07

There is evidence that chronic pharmacoresistant temporal lobe epilepsy (TLE) is a progressive disorder accompanied by mental deterioration. We investigated effects of aging on cerebral N-acetyl-aspartate (NAA) concentrations in the temporal lobe of 12 patients with pharmacoresistant mesial TLE (mTLE) and 22 healthy controls by means of proton-magnetic resonance spectroscopy ((1)H-MRS) at 3 T. Furthermore, we calculated correlations between NAA concentrations and measures of verbal and figural memory in patients. In mTLE patients but not in healthy controls the concentration of NAA in the lateral temporal lobe was negatively correlated with age. In patients with mTLE NAA in left lateral temporal voxels correlated with verbal memory. NAA in medial temporal voxels did not correlate with age or neuropsychological measures. Significant decrease of NAA with age in the lateral temporal lobe of patients with mTLE provides evidence for progressive neuronal dysfunction with aging. NAA is a marker of neuronal integrity since it correlates with verbal memory.

Distinctive Structural and Effective Connectivity Changes of Semantic Cognition Network across Left and Right Mesial Temporal Lobe Epilepsy Patients.

PubMed

Fan, Xiaotong; Yan, Hao; Shan, Yi; Shang, Kun; Wang, Xiaocui; Wang, Peipei; Shan, Yongzhi; Lu, Jie; Zhao, Guoguang

2016-01-01

Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients.

Distinctive Structural and Effective Connectivity Changes of Semantic Cognition Network across Left and Right Mesial Temporal Lobe Epilepsy Patients

PubMed Central

Fan, Xiaotong; Shang, Kun; Wang, Xiaocui; Wang, Peipei; Shan, Yongzhi; Lu, Jie

2016-01-01

Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients. PMID:28018680

Influence of anxiety on memory performance in temporal lobe epilepsy.

PubMed

Brown, Franklin C; Westerveld, Michael; Langfitt, John T; Hamberger, Marla; Hamid, Hamada; Shinnar, Shlomo; Sperling, Michael R; Devinsky, Orrin; Barr, William; Tracy, Joseph; Masur, David; Bazil, Carl W; Spencer, Susan S

2014-02-01

This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 patients with temporal lobe epilepsy from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was poorer for those with high versus low levels of anxiety but was not found to be related to the TLE side. The verbal memory score on the California Verbal Learning Test (CVLT) was significantly lower for patients with left-sided TLE than for patients with right-sided TLE with low anxiety levels but equally impaired for those with high anxiety levels. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left-sided TLE for those with low anxiety levels, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety levels. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety levels. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety levels. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among patients with TLE, regardless of anxiety levels. © 2013.

Evaluation of feature selection algorithms for classification in temporal lobe epilepsy based on MR images

NASA Astrophysics Data System (ADS)

Lai, Chunren; Guo, Shengwen; Cheng, Lina; Wang, Wensheng; Wu, Kai

2017-02-01

It's very important to differentiate the temporal lobe epilepsy (TLE) patients from healthy people and localize the abnormal brain regions of the TLE patients. The cortical features and changes can reveal the unique anatomical patterns of brain regions from the structural MR images. In this study, structural MR images from 28 normal controls (NC), 18 left TLE (LTLE), and 21 right TLE (RTLE) were acquired, and four types of cortical feature, namely cortical thickness (CTh), cortical surface area (CSA), gray matter volume (GMV), and mean curvature (MCu), were explored for discriminative analysis. Three feature selection methods, the independent sample t-test filtering, the sparse-constrained dimensionality reduction model (SCDRM), and the support vector machine-recursive feature elimination (SVM-RFE), were investigated to extract dominant regions with significant differences among the compared groups for classification using the SVM classifier. The results showed that the SVM-REF achieved the highest performance (most classifications with more than 92% accuracy), followed by the SCDRM, and the t-test. Especially, the surface area and gray volume matter exhibited prominent discriminative ability, and the performance of the SVM was improved significantly when the four cortical features were combined. Additionally, the dominant regions with higher classification weights were mainly located in temporal and frontal lobe, including the inferior temporal, entorhinal cortex, fusiform, parahippocampal cortex, middle frontal and frontal pole. It was demonstrated that the cortical features provided effective information to determine the abnormal anatomical pattern and the proposed method has the potential to improve the clinical diagnosis of the TLE.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

PubMed

Martínez-Levy, G A; Rocha, L; Rodríguez-Pineda, F; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Briones-Velasco, M; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

2018-05-01

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Rhythmic ictal nonclonic hand (RINCH) motions in temporal lobe epilepsy: invasive EEG findings, incidence, and lateralizing value.

PubMed

Kuba, Robert; Musilová, Klára; Vojvodič, Nikola; Tyrlíková, Ivana; Rektor, Ivan; Brázdil, Milan

2013-10-01

The main purpose of this retrospective analysis was to evaluate the incidence and lateralization value of rhythmic ictal nonclonic hand (RINCH) motions in patients with temporal lobe epilepsy (TLE), who were classified as Engel I at least 2 years after epilepsy surgery. We analyzed the distribution of ictal activity at the time of RINCH appearance in patients in whom RINCH motions were present during invasive EEG monitoring. A group of 120 patients was included in this study. In total, we reviewed 491 seizures: 277 seizures in patients with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (TLE-HS group) and 214 in TLE caused by other lesions (TLE-OTH group). We analyzed 29 patients (79 of the seizures) during invasive EEG monitoring. Fisher's exact test and binomial test were used for the statistical analysis. RINCH motions were observed in 24 out of 120 patients (20%) and in 48 out of 491 seizures (9.8%). There was no significant difference between the occurrence of RINCH motions in patients with TLE-HS and in patients with TLE-OTH, or between gender, right/left-sided TLE, and language dominant/nondominant TLE. RINCH motions were contralateral to the seizure onset in 83.3% of patients and 91.7% of seizures (p=0.0015; p<0.001, respectively). There were no differences in the lateralizing value of RINCH motions in patients with TLE-HS or TLE-OTH. We analyzed RINCH motions in 5 patients/7 seizures during invasive EEG. In all 7 seizures with RINCH motions, we observed the widespread activation of the temporal lobe (mesial and lateral, opercular and polar regions) contralateral to the side of RINCH motions. In all 7 seizures, we observed that at the time of RINCH motion onset, at least 1 explored region of the frontal lobe was affected by the ictal activity. In 3 seizures, we observed time-locked epileptic activation associated with the appearance of RINCH motions, i.e., in the orbitofrontal cortex in 2 seizures and in both the orbitofrontal cortex and anterior cingulate gyrus in 1 seizure. RINCH motions are a relatively frequent ictal sign in patients with TLE. They have a high lateralizing value in these patients, occurring contralateral to the ictal onset. RINCH motions usually occur after the spread of ictal activity beyond the temporal lobe, and their appearance is usually associated with the presence of ictal activity in various regions of the contralateral frontal lobe, mainly the orbitofrontal cortex and anterior cingulate gyrus. This is the first study analysing this phenomenon during invasive EEG recording. Copyright © 2013 Elsevier B.V. All rights reserved.

Machine learning approach for the outcome prediction of temporal lobe epilepsy surgery.

PubMed

Armañanzas, Rubén; Alonso-Nanclares, Lidia; Defelipe-Oroquieta, Jesús; Kastanauskaite, Asta; de Sola, Rafael G; Defelipe, Javier; Bielza, Concha; Larrañaga, Pedro

2013-01-01

Epilepsy surgery is effective in reducing both the number and frequency of seizures, particularly in temporal lobe epilepsy (TLE). Nevertheless, a significant proportion of these patients continue suffering seizures after surgery. Here we used a machine learning approach to predict the outcome of epilepsy surgery based on supervised classification data mining taking into account not only the common clinical variables, but also pathological and neuropsychological evaluations. We have generated models capable of predicting whether a patient with TLE secondary to hippocampal sclerosis will fully recover from epilepsy or not. The machine learning analysis revealed that outcome could be predicted with an estimated accuracy of almost 90% using some clinical and neuropsychological features. Importantly, not all the features were needed to perform the prediction; some of them proved to be irrelevant to the prognosis. Personality style was found to be one of the key features to predict the outcome. Although we examined relatively few cases, findings were verified across all data, showing that the machine learning approach described in the present study may be a powerful method. Since neuropsychological assessment of epileptic patients is a standard protocol in the pre-surgical evaluation, we propose to include these specific psychological tests and machine learning tools to improve the selection of candidates for epilepsy surgery.

Machine Learning Approach for the Outcome Prediction of Temporal Lobe Epilepsy Surgery

PubMed Central

DeFelipe-Oroquieta, Jesús; Kastanauskaite, Asta; de Sola, Rafael G.; DeFelipe, Javier; Bielza, Concha; Larrañaga, Pedro

2013-01-01

Epilepsy surgery is effective in reducing both the number and frequency of seizures, particularly in temporal lobe epilepsy (TLE). Nevertheless, a significant proportion of these patients continue suffering seizures after surgery. Here we used a machine learning approach to predict the outcome of epilepsy surgery based on supervised classification data mining taking into account not only the common clinical variables, but also pathological and neuropsychological evaluations. We have generated models capable of predicting whether a patient with TLE secondary to hippocampal sclerosis will fully recover from epilepsy or not. The machine learning analysis revealed that outcome could be predicted with an estimated accuracy of almost 90% using some clinical and neuropsychological features. Importantly, not all the features were needed to perform the prediction; some of them proved to be irrelevant to the prognosis. Personality style was found to be one of the key features to predict the outcome. Although we examined relatively few cases, findings were verified across all data, showing that the machine learning approach described in the present study may be a powerful method. Since neuropsychological assessment of epileptic patients is a standard protocol in the pre-surgical evaluation, we propose to include these specific psychological tests and machine learning tools to improve the selection of candidates for epilepsy surgery. PMID:23646148

Imaging structural and functional brain networks in temporal lobe epilepsy

PubMed Central

Bernhardt, Boris C.; Hong, SeokJun; Bernasconi, Andrea; Bernasconi, Neda

2013-01-01

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281

Subtle pathological changes in neocortical temporal lobe epilepsy.

PubMed

Ochoa, Juan G; Hentgarden, Diana; Paulzak, Audrey; Ogden, Melissa; Pryson, Richard; Lamle, Markus; Rusyniak, Walter G

2017-06-01

This was a prospective observational study to correlate the clinical symptoms, electrophysiology, imaging, and surgical pathology of patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis. We selected consecutive patients with TLE and normal MRI undergoing temporal lobe resection between April and September 2015. Clinical features, imaging, and functional data were reviewed. Intracranial monitoring and language mapping were performed when it was required according to our team recommendation. Prior to hippocampal resection, intraoperative electrocorticography was performed using depth electrodes in the amygdala and the hippocampus. The resected hippocampus was sent for pathological analysis. Five patients with diagnosis with non-lesional TLE were included. We did not find distinctive clinical features that could be a characteristic of non-lesional TLE. The mean follow-up was 13.2months (11-15months); 80% of patients achieved Engel Class I outcome. There was no distinctive electrographic findings in these patients. Histopathologic analysis was negative for mesial temporal sclerosis. A second blinded independent neuropathologist with expertise in epilepsy found ILAE type I focal cortical dysplasia in the parahippocampal gyrus in all patients. A third independent neuropathologist reported changes in layer 2 with larger pyramidal neurons in 4 cases but concluded that none of these cases met the diagnostic criteria of FCD. Subtle pathological changes could be associated with a parahippocampal epileptic zone and should be investigated in patients with MRI-negative TLE. This study also highlights the lack of interobserver reliability for the diagnosis of mild cortical dysplasia. Finally, selective amygdalo-hippocampectomy or laser ablation of the hippocampus may not control intractable epilepsy in this specific population. Copyright © 2017 Elsevier Inc. All rights reserved.

Aberrant topological patterns of brain structural network in temporal lobe epilepsy.

PubMed

Yasuda, Clarissa Lin; Chen, Zhang; Beltramini, Guilherme Coco; Coan, Ana Carolina; Morita, Marcia Elisabete; Kubota, Bruno; Bergo, Felipe; Beaulieu, Christian; Cendes, Fernando; Gross, Donald William

2015-12-01

Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

DTI-based response-driven modeling of mTLE laterality.

PubMed

Nazem-Zadeh, Mohammad-Reza; Elisevich, Kost; Air, Ellen L; Schwalb, Jason M; Divine, George; Kaur, Manpreet; Wasade, Vibhangini S; Mahmoudi, Fariborz; Shokri, Saeed; Bagher-Ebadian, Hassan; Soltanian-Zadeh, Hamid

2016-01-01

To develop lateralization models for distinguishing between unilateral and bilateral mesial temporal lobe epilepsy (mTLE) and determining laterality in cases of unilateral mTLE. mTLE is the most common form of medically refractory focal epilepsy. Many mTLE patients fail to demonstrate an unambiguous unilateral ictal onset. Intracranial EEG (icEEG) monitoring can be performed to establish whether the ictal origin is unilateral or truly bilateral with independent bitemporal ictal origin. However, because of the expense and risk of intracranial electrode placement, much research has been done to determine if the need for icEEG can be obviated with noninvasive neuroimaging methods, such as diffusion tensor imaging (DTI). Fractional anisotropy (FA) was used to quantify microstructural changes reflected in the diffusivity properties of the corpus callosum, cingulum, and fornix, in a retrospective cohort of 31 patients confirmed to have unilateral (n = 24) or bilateral (n = 7) mTLE. All unilateral mTLE patients underwent resection with an Engel class I outcome. Eleven were reported to have hippocampal sclerosis on pathological analysis; nine had undergone prior icEEG. The bilateral mTLE patients had undergone icEEG demonstrating independent epileptiform activity in both right and left hemispheres. Twenty-three nonepileptic subjects were included as controls. In cases of right mTLE, FA showed significant differences from control in all callosal subregions, in both left and right superior cingulate subregions, and in forniceal crura. Comparison of right and left mTLE cases showed significant differences in FA of callosal genu, rostral body, and splenium and the right posteroinferior and superior cingulate subregions. In cases of left mTLE, FA showed significant differences from control only in the callosal isthmus. Significant differences in FA were identified when cases of right mTLE were compared with bilateral mTLE cases in the rostral and midbody callosal subregions and isthmus. Based on 11 FA measurements in the cingulate, callosal and forniceal subregions, a response-driven lateralization model successfully differentiated all cases (n = 54) into groups of unilateral right (n = 12), unilateral left (n = 12), and bilateral mTLE (n = 7), and nonepileptic control (23). The proposed response-driven DTI biomarker is intended to lessen diagnostic ambiguity of laterality in cases of mTLE and help optimize selection of surgical candidates. Application of this model shows promise in reducing the need for invasive icEEG in prospective cases.

Pre- and post-operative Wisconsin card sorting test performance in patients with temporal lobe epilepsy due to hippocampal sclerosis

PubMed Central

Tisser, Luciana; Palmini, Andre; Paglioli, Eliseu; Portuguez, Mirna; Azambuja, Ney; da Costa, Jaderson Costa; Paglioli, Eduardo; Torres, Carolina; Martinez, Jose Victor

2007-01-01

Patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE/HS) have a distinct neuropsychological profile, but there is still debate on whether executive dysfunction is part of this profile and also whether temporal lobe surgery can modify this dysfunction. Objective To study the presence and reversibility of executive dysfunction in patients with unilateral TLE/HS. Methods Twenty-five patients with refractory seizures due to TLE/HS underwent presurgical evaluation which included the application of the Wiconsin Card Sorting Test (WCST). Nineteen were re-evaluated in follow up, at least 6 months after selective amygdalo-hippocampectomy (SAH). Twenty-two control subjects matched for age and education also performed the WCST. Results Sixteen of the 25 patients (64%) completed fewer than four categories in the WCST whereas only 4 of the 22 controls (18%) did not complete at least four categories (p<0.005). In addition, the performance of the patients involved significantly more perseverative responses and errors compared to controls. The patient group demonstrated significant post-operative improvement in many measures of the WCST following SAH. Conclusions These findings support the presence of executive dysfunction in patients with TLE/HS and suggest that such dysfunction can be partially reversed by selective resection of epileptogenic mesial temporal structures. PMID:29213385

Better Object Recognition and Naming Outcome With MRI-Guided Stereotactic Laser Amygdalohippocampotomy for Temporal Lobe Epilepsy

PubMed Central

Drane, Daniel L.; Loring, David W.; Voets, Natalie L.; Price, Michele; Ojemann, Jeffrey G.; Willie, Jon T.; Saindane, Amit M.; Phatak, Vaishali; Ivanisevic, Mirjana; Millis, Scott; Helmers, Sandra L.; Miller, John W.; Meador, Kimford J.; Gross, Robert E.

2015-01-01

SUMMARY OBJECTIVES Temporal lobe epilepsy (TLE) patients experience significant deficits in category-related object recognition and naming following standard surgical approaches. These deficits may result from a decoupling of core processing modules (e.g., language, visual processing, semantic memory), due to “collateral damage” to temporal regions outside the hippocampus following open surgical approaches. We predicted stereotactic laser amygdalohippocampotomy (SLAH) would minimize such deficits because it preserves white matter pathways and neocortical regions critical for these cognitive processes. METHODS Tests of naming and recognition of common nouns (Boston Naming Test) and famous persons were compared with nonparametric analyses using exact tests between a group of nineteen patients with medically-intractable mesial TLE undergoing SLAH (10 dominant, 9 nondominant), and a comparable series of TLE patients undergoing standard surgical approaches (n=39) using a prospective, non-randomized, non-blinded, parallel group design. RESULTS Performance declines were significantly greater for the dominant TLE patients undergoing open resection versus SLAH for naming famous faces and common nouns (F=24.3, p<.0001, η2=.57, & F=11.2, p<.001, η2=.39, respectively), and for the nondominant TLE patients undergoing open resection versus SLAH for recognizing famous faces (F=3.9, p<.02, η2=.19). When examined on an individual subject basis, no SLAH patients experienced any performance declines on these measures. In contrast, 32 of the 39 undergoing standard surgical approaches declined on one or more measures for both object types (p<.001, Fisher’s exact test). Twenty-one of 22 left (dominant) TLE patients declined on one or both naming tasks after open resection, while 11 of 17 right (non-dominant) TLE patients declined on face recognition. SIGNIFICANCE Preliminary results suggest 1) naming and recognition functions can be spared in TLE patients undergoing SLAH, and 2) the hippocampus does not appear to be an essential component of neural networks underlying name retrieval or recognition of common objects or famous faces. PMID:25489630

Comprehension and production of nouns and verbs in temporal lobe epilepsy.

PubMed

Yurchenko, Anna; Golovteev, Alexander; Kopachev, Dmitry; Dragoy, Olga

2017-10-01

Previous research on linguistic performance at the single-word level in patients with temporal lobe epilepsy (TLE) has mostly been limited to the comprehension and production of nouns, and findings have been inconsistent. Results are likewise limited and controversial regarding the lateralization of the epileptogenic focus. The present study investigates comprehension and production of nouns and verbs in patients with left and right TLE (12 in each group). We designed a comprehension (word-picture matching) test and a production (naming) test, matched on a range of psycholinguistic parameters for the two word classes. The results showed impaired verb comprehension in patients with left TLE and impaired noun and verb production in both groups of patients compared to the control group. Patients with left and right TLE differed significantly on verb comprehension and noun production, whereas verb production was equally impaired in the two groups of patients. These findings suggest difficulties with single-word processing in patients with both left and right TLE, which are more prominent for verbs than for nouns in patients with left TLE. The verb production (action naming) test turned out to be the most effective tool for assessing linguistic difficulties at the single-word level in patients with TLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Seizure semiology identifies patients with bilateral temporal lobe epilepsy.

PubMed

Loesch, Anna Mira; Feddersen, Berend; Tezer, F Irsel; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

2015-01-01

Laterality in temporal lobe epilepsy is usually defined by EEG and imaging results. We investigated whether the analysis of seizure semiology including lateralizing seizure phenomena identifies bilateral independent temporal lobe seizure onset. We investigated the seizure semiology in 17 patients in whom invasive EEG-video-monitoring documented bilateral temporal seizure onset. The results were compared to 20 left and 20 right consecutive temporal lobe epilepsy (TLE) patients who were seizure free after anterior temporal lobe resection. The seizure semiology was analyzed using the semiological seizure classification with particular emphasis on the sequence of seizure phenomena over time and lateralizing seizure phenomena. Statistical analysis included chi-square test or Fisher's exact test. Bitemporal lobe epilepsy patients had more frequently different seizure semiology (100% vs. 40%; p<0.001) and significantly more often lateralizing seizure phenomena pointing to bilateral seizure onset compared to patients with unilateral TLE (67% vs. 11%; p<0.001). The sensitivity of identical vs. different seizure semiology for the identification of bilateral TLE was high (100%) with a specificity of 60%. Lateralizing seizure phenomena had a low sensitivity (59%) but a high specificity (89%). The combination of lateralizing seizure phenomena and different seizure semiology showed a high specificity (94%) but a low sensitivity (59%). The analysis of seizure semiology including lateralizing seizure phenomena adds important clinical information to identify patients with bilateral TLE. Copyright © 2014 Elsevier B.V. All rights reserved.

The relationship between emotional intelligence and task-switching in temporal lobe epilepsy.

PubMed

Gul, Amara; Hussain, Imtiaz

2016-01-01

To examine the role of emotional intelligence (EI) in task-switching performance of patients with temporal lobe epilepsy (TLE). An experimental research design conducted at Sheikh Zayed Hospital, Rahim Yar Khan, Mayo and Services Hospital, Lahore, Pakistan from March 2013 to October 2014. Twenty-five patients with TLE and 25 healthy individuals from local community participated in the study. Participants completed measures of intelligence, EI, depression, anxiety, stress, and task-switching experiment. Patients and controls showed an average intelligence quotient, and normal levels of depression, anxiety, and stress. In contrast to controls, patients showed lower EI and impaired task-switching abilities. This result can be seen in the context of disintegrated white matter and cerebral connectivity in patients with TLE. Emotional intelligence was found to be a significant predictor of task-switching performance. Emotional intelligence is a potential marker of higher order cognitive functioning in patients with TLE.

Mapping thalamocortical network pathology in temporal lobe epilepsy.

PubMed

Bernhardt, Boris C; Bernasconi, Neda; Kim, Hosung; Bernasconi, Andrea

2012-01-10

Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

PubMed

Martínez-Levy, G A; Rocha, L; Lubin, F D; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Pérez-Molina, R; Briones-Velasco, M; Recillas-Targa, F; Pérez-Molina, A; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

2016-02-09

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Assessing a Metacognitive Account of Associative Memory Impairments in Temporal Lobe Epilepsy

PubMed Central

Kemp, Steven; Souchay, Céline; Moulin, Chris J. A.

2016-01-01

Previous research has pointed to a deficit in associative recognition in temporal lobe epilepsy (TLE). Associative recognition tasks require discrimination between various combinations of words which have and have not been seen previously (such as old-old or old-new pairs). People with TLE tend to respond to rearranged old-old pairs as if they are “intact” old-old pairs, which has been interpreted as a failure to use a recollection strategy to overcome the familiarity of two recombined words into a new pairing. We examined this specific deficit in the context of metacognition, using postdecision confidence judgements at test. We expected that TLE patients would show inappropriate levels of confidence for associative recognition. Although TLE patients reported lower confidence levels in their responses overall, they were sensitive to the difficulty of varying pair types in their judgements and gave significantly higher confidence ratings for their correct answers. We conclude that a strategic deficit is not at play in the associative recognition of people with TLE, insofar as they are able to monitor the status of their memory system. This adds to a growing body of research suggesting that recollection is impaired in TLE, but not metacognition. PMID:27721992

Frontal lobe function in temporal lobe epilepsy

PubMed Central

Stretton, J.; Thompson, P.J.

2012-01-01

Summary Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further. PMID:22100147

Amygdala enlargement and emotional responses in (autoimmune) temporal lobe epilepsy.

PubMed

Holtmann, Olga; Schlossmacher, Insa; Moenig, Constanze; Johnen, Andreas; Rutter, Lisa-Marie; Tenberge, Jan-Gerd; Schiffler, Patrick; Everding, Judith; Golombeck, Kristin S; Strippel, Christine; Dik, Andre; Schwindt, Wolfram; Wiendl, Heinz; Meuth, Sven G; Bruchmann, Maximilian; Melzer, Nico; Straube, Thomas

2018-06-22

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.

Influence of anxiety on memory performance in temporal lobe epilepsy

PubMed Central

Brown, Franklin C.; Westerveld, Michael; Langfitt, John T.; Hamberger, Marla; Hamid, Hamada; Shinnar, Shlomo; Sperling, Michael R.; Devinsky, Orrin; Barr, William; Tracy, Joseph; Masur, David; Bazil, Carl W.; Spencer, Susan S.

2013-01-01

This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 temporal lobe epilepsy patients from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was lower for those with high versus low level of anxiety, but was not found to be related to side of TLE. Verbal memory on the California Verbal Learning Test (CVLT) was significantly lower for left than right TLE patients with low anxiety, but equally impaired for those with high anxiety. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left TLE for those with low anxiety, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety level. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among TLE patients, regardless of anxiety level. PMID:24291525

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis.

PubMed

Rzezak, Patrícia; Lima, Ellen Marise; Gargaro, Ana Carolina; Coimbra, Erica; de Vincentiis, Silvia; Velasco, Tonicarlo Rodrigues; Leite, João Pereira; Busatto, Geraldo F; Valente, Kette D

2017-04-01

Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis.

PubMed

Jin, Seung-Hyun; Chung, Chun Kee

2015-10-01

Little is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance. Resting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE=22; right mTLE=19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS. Connectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE. Our results suggest that right hippocampal-left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal-frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of CXCR2 inhibition on seizure activity in the pilocarpine epilepsy mouse model.

PubMed

Xu, Tao; Yu, Xinyuan; Wang, Teng; Liu, Ying; Liu, Xi; Ou, Shu; Chen, Yangmei

2017-09-01

C-X-C motif chemokine receptor 2 (CXCR2) is one of the most well characterized chemokine receptors and is a potential target for treating brain pathologies involving inflammatory processes, including epilepsy. However, the role of CXCR2 in epilepsy has not been investigated, and whether CXCR2 modulates seizure activity in temporal lobe epilepsy (TLE) remains unknown. In this study, we aimed to determine the potential role of CXCR2 in intractable TLE patients and in pilocarpine-induced epileptic mice. Here, through Western blotting and semi-quantitative immunohistochemistry, we detected that CXCR2 protein expression was up-regulated (by nearly 50%) in the temporal neocortex of TLE patients and in the hippocampus and adjacent temporal cortex of pilocarpine mice model. Double-label immunofluorescence and immunohistochemical analysis indicated that CXCR2 was expressed in neurons. To investigate the effect of the CXCR2 selective antagonist SB225002 on seizure activity, SB225002 was i.p. administered during the latency window of spontaneous recurrent seizures (SRSs). This treatment increased (by nearly 40%) the latency of SRSs and reduced (by nearly 50%) the frequency of SRSs during the chronic period of epilepsy. This study suggests that CXCR2 plays a critical role in modifying epileptic seizure activity and that CXCR2 blockade could be a potential molecular therapeutic target for epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Accelerated long-term forgetting and behavioural difficulties in children with epilepsy.

PubMed

Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

2018-03-30

Patients with epilepsy have been shown to exhibit a range of memory deficits, including the rapid forgetting of newly-learned material over long, but not short, delays (termed accelerated long-term forgetting; ALF). Behavioural problems, such as mood disorders and social difficulties, are also overrepresented among children with epilepsy, when compared to patients with other chronic diseases and the general population. We investigated whether ALF was associated with behavioural or psychosocial deficits in children with epilepsy. Patients with either idiopathic generalised epilepsy (IGE; n = 20) or temporal lobe epilepsy (TLE; n = 23) and healthy controls (n = 53) of comparable age, sex, and socioeconomic status completed a battery of neuropsychological tests, including a list-learning task that required recall after short (30-min) and long (7-day) delays. Parents or guardians of all participants also completed the Child Behavior Checklist (CBCL). Compared to control participants, patients with IGE and TLE had higher scores on all but one of the indices of behavioural problems. When patients with IGE and TLE were merged into a single group, they were found to have negative correlations between 7-day recall and internalising, social and total problem behaviour domains, where poorer 7-day recall was associated with behavioural problems of greater severity. These findings suggest that impaired episodic recall is associated with behavioural deficits, including social problems, which are routinely observed in patients with epilepsy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recognition and identification of famous faces in patients with unilateral temporal lobe epilepsy.

PubMed

Seidenberg, Michael; Griffith, Randall; Sabsevitz, David; Moran, Maria; Haltiner, Alan; Bell, Brian; Swanson, Sara; Hammeke, Thomas; Hermann, Bruce

2002-01-01

We examined the performance of 21 patients with unilateral temporal lobe epilepsy (TLE) and hippocampal damage (10 lefts, and 11 rights) and 10 age-matched controls on the recognition and identification (name and occupation) of well-known faces. Famous face stimuli were selected from four time periods; 1970s, 1980s, 1990-1994, and 1995-1996. Differential patterns of performance were observed for the left and right TLE group across distinct face processing components. The left TLE group showed a selective impairment in naming famous faces while they performed similar to the controls in face recognition and semantic identification (i.e. occupation). In contrast, the right TLE group was impaired across all components of face memory; face recognition, semantic identification, and face naming. Face naming impairment in the left TLE group was characterized by a temporal gradient with better naming performance for famous faces from more distant time periods. Findings are discussed in terms of the role of the temporal lobe system for the acquisition, retention, and retrieval of face semantic networks, and the differential effects of lateralized temporal lobe lesions in this process.

Semantic Processing Impairment in Patients with Temporal Lobe Epilepsy

PubMed Central

Jaimes-Bautista, Amanda G.; Rodríguez-Camacho, Mario; Martínez-Juárez, Iris E.; Rodríguez-Agudelo, Yaneth

2015-01-01

The impairment in episodic memory system is the best-known cognitive deficit in patients with temporal lobe epilepsy (TLE). Recent studies have shown evidence of semantic disorders, but they have been less studied than episodic memory. The semantic dysfunction in TLE has various cognitive manifestations, such as the presence of language disorders characterized by defects in naming, verbal fluency, or remote semantic information retrieval, which affects the ability of patients to interact with their surroundings. This paper is a review of recent research about the consequences of TLE on semantic processing, considering neuropsychological, electrophysiological, and neuroimaging findings, as well as the functional role of the hippocampus in semantic processing. The evidence from these studies shows disturbance of semantic memory in patients with TLE and supports the theory of declarative memory of the hippocampus. Functional neuroimaging studies show an inefficient compensatory functional reorganization of semantic networks and electrophysiological studies show a lack of N400 effect that could indicate that the deficit in semantic processing in patients with TLE could be due to a failure in the mechanisms of automatic access to lexicon. PMID:26257956

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

Spike voltage topography in temporal lobe epilepsy.

PubMed

Asadi-Pooya, Ali A; Asadollahi, Marjan; Shimamoto, Shoichi; Lorenzo, Matthew; Sperling, Michael R

2016-07-15

We investigated the voltage topography of interictal spikes in patients with temporal lobe epilepsy (TLE) to see whether topography was related to etiology for TLE. Adults with TLE, who had epilepsy surgery for drug-resistant seizures from 2011 until 2014 at Jefferson Comprehensive Epilepsy Center were selected. Two groups of patients were studied: patients with mesial temporal sclerosis (MTS) on MRI and those with other MRI findings. The voltage topography maps of the interictal spikes at the peak were created using BESA software. We classified the interictal spikes as polar, basal, lateral, or others. Thirty-four patients were studied, from which the characteristics of 340 spikes were investigated. The most common type of spike orientation was others (186 spikes; 54.7%), followed by lateral (146; 42.9%), polar (5; 1.5%), and basal (3; 0.9%). Characteristics of the voltage topography maps of the spikes between the two groups of patients were somewhat different. Five spikes in patients with MTS had polar orientation, but none of the spikes in patients with other MRI findings had polar orientation (odds ratio=6.98, 95% confidence interval=0.38 to 127.38; p=0.07). Scalp topographic mapping of interictal spikes has the potential to offer different information than visual inspection alone. The present results do not allow an immediate clinical application of our findings; however, detecting a polar spike in a patient with TLE may increase the possibility of mesial temporal sclerosis as the underlying etiology. Copyright © 2016 Elsevier B.V. All rights reserved.

Outcome of temporal lobe epilepsy surgery evaluated with bitemporal intracranial electrode recordings.

PubMed

Massot-Tarrús, Andreu; Steven, David A; McLachlan, Richard S; Mirsattari, Seyed M; Diosy, David; Parrent, Andrew G; Blume, Warren T; Girvin, John P; Burneo, Jorge G

2016-11-01

Temporal lobe epilepsy (TLE) with unclear lateralization may require intracranial implantation of electrodes (IIE). We retrospectively assessed the association between the use of IIE and long-term outcomes in patients undergoing anterior temporal lobectomy (ATL). We retrospectively reviewed the records of 1,032 patients undergoing epilepsy surgery at our center from 1977 to 2006. Patients who underwent ATL were included. Seizure outcome was assessed through final follow-up. Those who underwent scalp and IIE (mostly evaluated with temporal subdural strip electrodes) were compared. From 497 patients who underwent ATL, 139 did so after IIE placement in the temporal lobes. Mean age at surgery was 32.3±12.3years and median duration of follow-up 24 months (range: 6-36). Fifty-three percent of those evaluated with IIE were seizure-free at their last available visit (vs. 68% evaluated with only scalp EEG, p=0.002). Patients with lesional TLE generally had a better outcome (65.5% seizure free) than those without lesions (56.3%, p=0.093), especially for unilateral TLE diagnosed with IIE. In a multivariate Cox regression analyses adjusted for gender, neuropsychological concordance, pathological findings, and post-operative seizures, bilateral TLE predicted seizure recurrence in IIE patients (HR=2.08, 95% CI: 1.08-4.0, p=0.029). More than a half of those who undergo IIE in suspected TLE are seizure free after ATL. IIE allows for the identification of surgical candidates. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel GABRG2 mutations cause familial febrile seizures.

PubMed

Boillot, Morgane; Morin-Brureau, Mélanie; Picard, Fabienne; Weckhuysen, Sarah; Lambrecq, Virginie; Minetti, Carlo; Striano, Pasquale; Zara, Federico; Iacomino, Michele; Ishida, Saeko; An-Gourfinkel, Isabelle; Daniau, Mailys; Hardies, Katia; Baulac, Michel; Dulac, Olivier; Leguern, Eric; Nabbout, Rima; Baulac, Stéphanie

2015-12-01

To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy. The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening. Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.Pro59fs*12), 1 missense mutation (p.Met199Val), and 1 exonic deletion were subsequently identified in 5 families of the follow-up cohort. We report GABRG2 mutations in 5.6% (6/108) of families with FS, with or without associated epilepsy. This study provides evidence that GABRG2 mutations are linked to the FS phenotype, rather than epilepsy, and that loss-of-function of GABAA receptor γ2 subunit is the probable underlying pathogenic mechanism.

Treatment of depression in patients with temporal lobe epilepsy: A pilot study of cognitive behavioral therapy vs. selective serotonin reuptake inhibitors.

PubMed

Orjuela-Rojas, Juan Manuel; Martínez-Juárez, Iris E; Ruiz-Chow, Angel; Crail-Melendez, Daniel

2015-10-01

There is a high prevalence of depression in patients with epilepsy, which negatively impacts their quality of life (QOL) and seizure control. Currently, the first-line of treatment for depression in patients with epilepsy is based on selective serotonin reuptake inhibitors (SSRIs). The main objective of this pilot study was to compare cognitive behavioral therapy (CBT) versus SSRIs for the treatment of major depressive disorder (MDD) in patients with temporal lobe epilepsy (TLE). Seven patients who received group CBT were compared with eight patients treated with SSRIs. All were diagnosed with MDD and TLE. Patients were assessed at baseline before treatment and at six and 12weeks during treatment with the Quality of Life in Epilepsy Scale of 31 items (QOLIE 31), the Beck Depression Inventory (BDI), and the Hospital Anxiety and Depression Scale (HADS). Seizure records were also taken on a monthly basis. After 12weeks of treatment, both groups showed improved QOL and reduced severity of depression symptoms. There were no statistically significant group differences in the final scores for the BDI (p=0.40) and QOLIE 31 (p=0.72), although the effect size on QOL was higher for the group receiving CBT. In conclusion, the present study suggests that both CBT and SSRIs may improve MDD and QOL in patients with TLE. We found no significant outcome differences between both treatment modalities. These findings support further study using a double-blind controlled design to demonstrate the efficacy of CBT and SSRIs in the treatment of MDD and QOL in patients with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory.

PubMed

Kellermann, Tanja S; Bonilha, Leonardo; Eskandari, Ramin; Garcia-Ramos, Camille; Lin, Jack J; Hermann, Bruce P

2016-10-01

Normal cognitive function is defined by harmonious interaction among multiple neuropsychological domains. Epilepsy has a disruptive effect on cognition, but how diverse cognitive abilities differentially interact with one another compared with healthy controls (HC) is unclear. This study used graph theory to analyze the community structure of cognitive networks in adults with temporal lobe epilepsy (TLE) compared with that in HC. Neuropsychological assessment was performed in 100 patients with TLE and 82 HC. For each group, an adjacency matrix was constructed representing pair-wise correlation coefficients between raw scores obtained in each possible test combination. For each cognitive network, each node corresponded to a cognitive test; each link corresponded to the correlation coefficient between tests. Global network structure, community structure, and node-wise graph theory properties were qualitatively assessed. The community structure in patients with TLE was composed of fewer, larger, more mixed modules, characterizing three main modules representing close relationships between the following: 1) aspects of executive function (EF), verbal and visual memory, 2) speed and fluency, and 3) speed, EF, perception, language, intelligence, and nonverbal memory. Conversely, controls exhibited a relative division between cognitive functions, segregating into more numerous, smaller modules consisting of the following: 1) verbal memory, 2) language, perception, and intelligence, 3) speed and fluency, and 4) visual memory and EF. Overall node-wise clustering coefficient and efficiency were increased in TLE. Adults with TLE demonstrate a less clear and poorly structured segregation between multiple cognitive domains. This panorama suggests a higher degree of interdependency across multiple cognitive domains in TLE, possibly indicating compensatory mechanisms to overcome functional impairments. Copyright © 2016 Elsevier Inc. All rights reserved.

The temporal relation between seizure onset and arousal-awakening in temporal lobe seizures.

PubMed

Gumusyayla, Sadiye; Erdal, Abidin; Tezer, F Irsel; Saygi, Serap

2016-07-01

Our main aim was to determine the time interval between the seizure onsets and arousal-awakening related to these seizures in patients with temporal lobe epilepsy (TLE) and to discuss the role of lateralization on arousal-awakening mechanisms. Thirty-three TLE patients who underwent video-EEG monitoring with simultaneous polysomnography (PSG) and had recorded nocturnal seizures were retrospectively examined. These TLE patients had 64 seizures during sleep. The onsets of seizures and arousal-awakening related to these seizures were marked according to clinical and electrophysiological features. The time interval between the seizure onset and arousal-awakening related to the seizure was compared in patients with right- or left-sided temporal lobe seizures. In our TLE patients nocturnal seizures mostly followed arousal-awakening (64%). The time interval between the seizure onset and arousal-awakening related to the seizure was significantly shorter in patients with left-sided temporal lobe seizures (p=0.01). Video-EEG monitoring and PSG with scalp electrodes in our TLE patients showed that nocturnal seizures mostly followed arousal-awakening, and it was more pronounced in those with left-sided seizures. Arousal-awakening might be a signal for subsequent seizures in patients with TLE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy.

PubMed

Han, Chun-Lei; Ge, Ming; Liu, Yun-Peng; Zhao, Xue-Min; Wang, Kai-Liang; Chen, Ning; Hu, Wei; Zhang, Jian-Guo; Li, Liang; Meng, Fan-Gang

2018-05-23

Temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy, characterized by hippocampal neuron damage and hippocampal sclerosis. Long noncoding RNAs (lncRNAs) have been increasingly recognized as posttranscriptional regulators. However, their expression levels and functions in TLE remain largely unknown. In the present study, TLE rat model is used to explore the expression profiles of lncRNAs in the hippocampus of epileptic rats using microarray analysis. Our results demonstrate that H19 is the most pronouncedly differentiated lncRNA, significantly upregulated in the latent period of TLE. Moreover, the in vivo studies using gain- and loss-of-function approaches reveal that the overexpression of H19 aggravates SE-induced neuron apoptosis in the hippocampus, while inhibition of H19 protects the rats from SE-induced cellular injury. Finally, we show that H19 might function as a competing endogenous RNA to sponge microRNA let-7b in the regulation of cellular apoptosis. Overall, our study reveals a novel lncRNA H19-mediated mechanism in seizure-induced neural damage and provides a new target in developing lncRNA-based strategies to reduce seizure-induced brain injury.

Systematic Review of Cognitive Function in Euthymic Bipolar Disorder and Pre-Surgical Temporal Lobe Epilepsy.

PubMed

Bostock, Emmanuelle C S; Kirkby, Kenneth C; Garry, Michael I; Taylor, Bruce V M

2017-01-01

Bipolar disorder (BD) and temporal lobe epilepsy (TLE) overlap in domains including epidemiology, treatment response, shared neurotransmitter involvement and temporal lobe pathology. Comparison of cognitive function in both disorders may indicate temporal lobe mediated processes relevant to BD. This systematic review examines neuropsychological test profiles in euthymic bipolar disorder type I (BD-I) and pre-surgical TLE and compares experimental designs used. A search of PubMed, PsychINFO, and Scopus using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. Inclusion criteria were comparison group or pre- to post-surgical patients; reported neuropsychological tests; participants aged 18-60 years. Fifty six studies met criteria: 27 BD-I; 29 TLE. Deficits in BD-I compared to healthy controls (HC) were in executive function, attention span and verbal memory. Deficits in TLE compared to HC were in executive function and memory. In the pre- to post-surgical comparisons, verbal memory in left temporal lobe (LTL) and, less consistently, visuospatial memory in right temporal lobe (RTL) epilepsy declined following surgery. BD-I studies used comprehensive test batteries in well-defined euthymic patients compared to matched HC groups. TLE studies used convenience samples pre- to post-surgery, comparing LTL and RTL subgroups, few included comparisons to HC (5 studies). TLE studies typically examined a narrow range of known temporal lobe-mediated neuropsychological functions, particularly verbal and visuospatial memory. Both disorders exhibit deficits in executive function and verbal memory suggestive of both frontal and temporal lobe involvement. However, deficits in TLE are measured pre- to post-surgery and not controlled at baseline pre-surgery. Further research involving a head-to-head comparison of the two disorders on a broad range of neuropsychological tests is needed to clarify the nature and extent of cognitive deficits and potential overlaps.

Remembrance and time passed: Memory outcomes 4-11 years after pediatric epilepsy surgery.

PubMed

Puka, Klajdi; Smith, Mary Lou

2016-11-01

Little is known about the long-term cognitive outcomes following pediatric epilepsy surgery. Although the evidence for change within the first 2 years is not compelling, the plasticity of the immature brain may allow for improvements in the long term. This study examined memory function in a cohort of surgical and nonsurgical patients at baseline and 4-11 years after. Participants were 88 patients (mean age 20.05, standard deviation [SD] 4.21 years) with childhood-onset intractable epilepsy; 53 had undergone resective epilepsy surgery. Verbal and visual memory were assessed at baseline and follow-up using standardized tests of recall of stories, faces, word pairs, and word lists. Improvements over time were not found; outcomes were largely independent of surgical status. Those who were seizure-free at follow-up had better story recall at both times (p = 0.028), and did not show improvement. Among patients with extratemporal lobe epilepsy, significant declines in word list recall were found over time irrespective of surgical or seizure status (p = 0.010). Effects of laterality of seizure focus were evident only when examining patients with temporal lobe epilepsy (TLE); patients with left TLE had lower story recall scores compared to patients with right TLE at long-term follow-up (p = 0.043). Patients who became seizure-free had some advantages in memory, but did not show improvements over time. These findings have important implications for understanding potential outcomes from surgery or continued use of antiepileptic medications. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Effect of EEG Biofeedback on Cognitive Flexibility in Children with Attention Deficit Hyperactivity Disorder With and Without Epilepsy.

PubMed

Bakhtadze, Sophia; Beridze, Maia; Geladze, Nana; Khachapuridze, Nana; Bornstein, Natan

2016-03-01

Attention deficit hyperactivity disorder (ADHD) is one of the most common developmental disorders in school-aged children. Symptoms consistent with ADHD have been observed in 8-77 % of children with epilepsy. Researchers have been motivated to search for alternative forms of treatment because 30 % of patients with ADHD cannot be treated by psychostimulants. Several studies support the use of a multimodal treatment approach that includes neurofeedback (NF) for the long-term management of ADHD. These studies have shown that NF provides a sustained effect, even without concurrent treatment with stimulants. We aimed to assess cognitive flexibility in ADHD children with and without temporal lobe epilepsy (TLE), and to evaluate the effects of NF on cognitive flexibility in these groups of children. We prospectively evaluated 69 patients with ADHD aged 9-12 years. The control group was 26 ADHD children without TLE who received no treatment. The first experimental group comprised 18 children with ADHD. The second experimental group comprised 25 age-matched ADHD children with TLE. This group was further divided in two subgroups. One subgroup comprised those with mesial temporal lobe epilepsy (16 patients, 9 with hippocampal sclerosis and 7 with hippocampal atrophy), and the other with lateral temporal lobe epilepsy (9 patients, 5 with temporal lobe dysplasia, 3 with temporal lobe cysts, and 1 with a temporal lobe cavernoma). We treated their ADHD by conducting 30 sessions of EEG NF. Reaction time and error rates on the Trail Making Test Part B were compared before and after treatment, and significant differences were found for all groups of patients except those who had mesial temporal lobe epilepsy with hippocampal atrophy. Our results demonstrate that in most cases, NF can be considered an alternative treatment option for ADHD children even if they have TLE. Additional studies are needed to confirm our results.

Heightened Background Cortical Synchrony in Patients With Epilepsy: EEG Phase Synchrony Analysis During Awake and Sleep Stages Using Novel Ensemble Measure.

PubMed

Nayak, Chetan S; Mariyappa, N; Majumdar, Kaushik K; Prasad, Pradeep D; Ravi, G S; Nagappa, M; Kandavel, Thennarasu; Taly, Arun B; Sinha, Sanjib

2018-05-01

Excessive cortical synchrony within neural ensembles has been implicated as an important mechanism driving epileptiform activity. The current study measures and compares background electroencephalographic (EEG) phase synchronization in patients having various types of epilepsies and healthy controls during awake and sleep stages. A total of 120 patients with epilepsy (PWE) subdivided into 3 groups (juvenile myoclonic epilepsy [JME], temporal lobe epilepsy [TLE], and extra-temporal lobe epilepsy [Ex-TLE]; n = 40 in each group) and 40 healthy controls were subjected to overnight polysomnography. EEG phase synchronization (SI) between the 8 EEG channels was assessed for delta, theta, alpha, sigma, and high beta frequency bands using ensemble measure on 10-second representative time windows and compared between patients and controls and also between awake and sleep stages. Mean ± SD of SI was compared using 2-way analysis of variance followed by pairwise comparison ( P ≤ .05). In both delta and theta bands, the SI was significantly higher in patients with JME, TLE, and Ex-TLE compared with controls, whereas in alpha, sigma, and high beta bands, SI was comparable between the groups. On comparison of SI between sleep stages, delta band: progressive increase in SI from wake ⇒ N1 ⇒ N2 ⇒ N3, whereas REM (rapid eye movement) was comparable to wake; theta band: decreased SI during N2 and increase during N3; alpha band: SI was highest in wake and lower in N1, N2, N3, and REM; and sigma and high beta bands: progressive increase in SI from wake ⇒ N1 ⇒ N2 ⇒ N3; however, sigma band showed lower SI during REM. This study found an increased background cortical synchronization in PWE compared with healthy controls in delta and theta bands during wake and sleep. This background hypersynchrony may be an important property of epileptogenic brain circuitry in PWE, which enables them to effortlessly generate a paroxysmal EEG depolarization shift.

Psychogenic nonepileptic seizures in patients with surgically treated temporal lobe epilepsy: Presurgical and de novo postsurgical occurrence.

PubMed

González Otárula, Karina A; Tan, Yee-Leng; Dubeau, François; Correa, José A; Chang, Edward; Hall, Jeffery A; Knowlton, Robert C; Kobayashi, Eliane

2017-10-01

Whether occurring before or after an epilepsy surgery, psychogenic nonepileptic seizures (PNES) impact treatment options and quality of life of patients with epilepsy. We investigated the frequency of pre- and postsurgical PNES, and the postsurgical Engel and psychiatric outcomes in patients with drug-resistant temporal lobe epilepsy (TLE). We reviewed 278 patients with mean age at surgery of 37.1±12.4years. Postsurgical follow-up information was available in 220 patients, with average follow-up of 4years. Nine patients (9/278 or 3.2%) had presurgical documented PNES. Eight patients (8/220 or 3.6%) developed de novo PNES after surgery. Pre- and postsurgery psychiatric comorbidities were similar to the patients without PNES. After surgery, in the group with presurgical PNES, five patients were seizure-free, and three presented persistent PNES. In the group with de novo postsurgery PNES, 62.5% had Engel II-IV, and 37.5% had Engel I. All presented PNES at last follow-up. Presurgical video-EEG monitoring is crucial in the diagnosis of coexisting PNES. Patients presenting presurgical PNES and drug-resistant TLE should not be denied surgery based on this comorbidity, as they can have good postsurgical epilepsy and psychiatric outcomes. Psychogenic nonepileptic seizures may appear after TLE surgery in a low but noteworthy proportion of patients regardless of the Engel outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Better object recognition and naming outcome with MRI-guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy.

PubMed

Drane, Daniel L; Loring, David W; Voets, Natalie L; Price, Michele; Ojemann, Jeffrey G; Willie, Jon T; Saindane, Amit M; Phatak, Vaishali; Ivanisevic, Mirjana; Millis, Scott; Helmers, Sandra L; Miller, John W; Meador, Kimford J; Gross, Robert E

2015-01-01

Patients with temporal lobe epilepsy (TLE) experience significant deficits in category-related object recognition and naming following standard surgical approaches. These deficits may result from a decoupling of core processing modules (e.g., language, visual processing, and semantic memory), due to "collateral damage" to temporal regions outside the hippocampus following open surgical approaches. We predicted that stereotactic laser amygdalohippocampotomy (SLAH) would minimize such deficits because it preserves white matter pathways and neocortical regions that are critical for these cognitive processes. Tests of naming and recognition of common nouns (Boston Naming Test) and famous persons were compared with nonparametric analyses using exact tests between a group of 19 patients with medically intractable mesial TLE undergoing SLAH (10 dominant, 9 nondominant), and a comparable series of TLE patients undergoing standard surgical approaches (n=39) using a prospective, nonrandomized, nonblinded, parallel-group design. Performance declines were significantly greater for the patients with dominant TLE who were undergoing open resection versus SLAH for naming famous faces and common nouns (F=24.3, p<0.0001, η2=0.57, and F=11.2, p<0.001, η2=0.39, respectively), and for the patients with nondominant TLE undergoing open resection versus SLAH for recognizing famous faces (F=3.9, p<0.02, η2=0.19). When examined on an individual subject basis, no SLAH patients experienced any performance declines on these measures. In contrast, 32 of the 39 patients undergoing standard surgical approaches declined on one or more measures for both object types (p<0.001, Fisher's exact test). Twenty-one of 22 left (dominant) TLE patients declined on one or both naming tasks after open resection, while 11 of 17 right (nondominant) TLE patients declined on face recognition. Preliminary results suggest (1) naming and recognition functions can be spared in TLE patients undergoing SLAH, and (2) the hippocampus does not appear to be an essential component of neural networks underlying name retrieval or recognition of common objects or famous faces. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy.

PubMed

Li, Jiaxin; Lin, Haijun; Sun, Zhenrong; Kong, Guanyi; Yan, Xu; Wang, Yujiao; Wang, Xiaoxuan; Wen, Yanhua; Liu, Xiang; Zheng, Hongkun; Jia, Mei; Shi, Zhongfang; Xu, Rong; Yang, Shaohua; Yuan, Fang

2018-01-01

Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Disentangling the cognitive components supporting Austin Maze performance in left versus right temporal lobe epilepsy.

PubMed

Hocking, Julia; Thomas, Hannah J; Dzafic, Ilvana; Williams, Rebecca J; Reutens, David C; Spooner, Donna M

2013-12-01

Neuropsychological tests requiring patients to find a path through a maze can be used to assess visuospatial memory performance in temporal lobe pathology, particularly in the hippocampus. Alternatively, they have been used as a task sensitive to executive function in patients with frontal lobe damage. We measured performance on the Austin Maze in patients with unilateral left and right temporal lobe epilepsy (TLE), with and without hippocampal sclerosis, compared to healthy controls. Performance was correlated with a number of other neuropsychological tests to identify the cognitive components that may be associated with poor Austin Maze performance. Patients with right TLE were significantly impaired on the Austin Maze task relative to patients with left TLE and controls, and error scores correlated with their performance on the Block Design task. The performance of patients with left TLE was also impaired relative to controls; however, errors correlated with performance on tests of executive function and delayed recall. The presence of hippocampal sclerosis did not have an impact on maze performance. A discriminant function analysis indicated that the Austin Maze alone correctly classified 73.5% of patients as having right TLE. In summary, impaired performance on the Austin Maze task is more suggestive of right than left TLE; however, impaired performance on this visuospatial task does not necessarily involve the hippocampus. The relationship of the Austin Maze task with other neuropsychological tests suggests that differential cognitive components may underlie performance decrements in right versus left TLE. © 2013.

Etiology of hippocampal sclerosis

PubMed Central

Tsai, Meng-Han; Pardoe, Heath R.; Perchyonok, Yuliya; Fitt, Gregory J.; Scheffer, Ingrid E.; Berkovic, Samuel F.

2013-01-01

Objective: We sought evidence of a hereditary component for hippocampal sclerosis (HS) by determining whether close relatives of probands with temporal lobe epilepsy (TLE) with HS also had asymptomatic HS or subtle variation in hippocampal morphology. Methods: First-degree relatives from 15 families in which probands had TLE with HS and 32 age- and sex-matched controls were included in the study. Left and right hippocampal volumes and T2 relaxometry were measured using 3-tesla MRI. Results: Thirty-two asymptomatic first-degree relatives and 3 relatives with a history of seizures or epilepsy were studied. None of the first-degree relatives had HS on visual analysis and T2 relaxation times were normal, excluding the presence of HS. Mean hippocampal volume was smaller (6.4%) in asymptomatic relatives (2.94 ± 0.27 cm3, 95% confidence interval = 2.87–3.01) than in controls (3.14 ± 0.22 cm3, 95% confidence interval = 3.09–3.19, p < 0.005); the effect was greater in relatives of probands with a positive family history of epilepsy. The relatives also had more asymmetric hippocampi (asymmetric index 0.92 ± 0.05) than controls (0.96 ± 0.03, p = 0.001). Conclusions: Small asymmetric hippocampi in healthy relatives are likely to represent a familial developmental variant that may predispose to the formation of TLE with HS. The underlying histopathology of these small hippocampi is unknown. This observation may provide an imaging marker for future studies seeking susceptibility genes for HS. PMID:23749796

Approximate Entropies for Stochastic Time Series and EKG Time Series of Patients with Epilepsy and Pseudoseizures

NASA Astrophysics Data System (ADS)

Vyhnalek, Brian; Zurcher, Ulrich; O'Dwyer, Rebecca; Kaufman, Miron

2009-10-01

A wide range of heart rate irregularities have been reported in small studies of patients with temporal lobe epilepsy [TLE]. We hypothesize that patients with TLE display cardiac dysautonomia in either a subclinical or clinical manner. In a small study, we have retrospectively identified (2003-8) two groups of patients from the epilepsy monitoring unit [EMU] at the Cleveland Clinic. No patients were diagnosed with cardiovascular morbidities. The control group consisted of patients with confirmed pseudoseizures and the experimental group had confirmed right temporal lobe epilepsy through a seizure free outcome after temporal lobectomy. We quantified the heart rate variability using the approximate entropy [ApEn]. We found similar values of the ApEn in all three states of consciousness (awake, sleep, and proceeding seizure onset). In the TLE group, there is some evidence for greater variability in the awake than in either the sleep or proceeding seizure onset. Here we present results for mathematically-generated time series: the heart rate fluctuations ξ follow the γ statistics i.e., p(ξ)=γ-1(k) ξ^k exp(-ξ). This probability function has well-known properties and its Shannon entropy can be expressed in terms of the γ-function. The parameter k allows us to generate a family of heart rate time series with different statistics. The ApEn calculated for the generated time series for different values of k mimic the properties found for the TLE and pseudoseizure group. Our results suggest that the ApEn is an effective tool to probe differences in statistics of heart rate fluctuations.

Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study.

PubMed

Luo, Cheng; Qiu, Chuan; Guo, Zhiwei; Fang, Jiajia; Li, Qifu; Lei, Xu; Xia, Yang; Lai, Yongxiu; Gong, Qiyong; Zhou, Dong; Yao, Dezhong

2011-01-01

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

PubMed

McCormick, Cornelia; Quraan, Maher; Cohn, Melanie; Valiante, Taufik A; McAndrews, Mary Pat

2013-05-01

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Predicting seizures in untreated temporal lobe epilepsy using point-process nonlinear models of heartbeat dynamics.

PubMed

Valenza, G; Romigi, A; Citi, L; Placidi, F; Izzi, F; Albanese, M; Scilingo, E P; Marciani, M G; Duggento, A; Guerrisi, M; Toschi, N; Barbieri, R

2016-08-01

Symptoms of temporal lobe epilepsy (TLE) are frequently associated with autonomic dysregulation, whose underlying biological processes are thought to strongly contribute to sudden unexpected death in epilepsy (SUDEP). While abnormal cardiovascular patterns commonly occur during ictal events, putative patterns of autonomic cardiac effects during pre-ictal (PRE) periods (i.e. periods preceding seizures) are still unknown. In this study, we investigated TLE-related heart rate variability (HRV) through instantaneous, nonlinear estimates of cardiovascular oscillations during inter-ictal (INT) and PRE periods. ECG recordings from 12 patients with TLE were processed to extract standard HRV indices, as well as indices of instantaneous HRV complexity (dominant Lyapunov exponent and entropy) and higher-order statistics (bispectra) obtained through definition of inhomogeneous point-process nonlinear models, employing Volterra-Laguerre expansions of linear, quadratic, and cubic kernels. Experimental results demonstrate that the best INT vs. PRE classification performance (balanced accuracy: 73.91%) was achieved only when retaining the time-varying, nonlinear, and non-stationary structure of heartbeat dynamical features. The proposed approach opens novel important avenues in predicting ictal events using information gathered from cardiovascular signals exclusively.

Brain Graph Topology Changes Associated with Anti-Epileptic Drug Use

PubMed Central

Levin, Harvey S.; Chiang, Sharon

2015-01-01

Abstract Neuroimaging studies of functional connectivity using graph theory have furthered our understanding of the network structure in temporal lobe epilepsy (TLE). Brain network effects of anti-epileptic drugs could influence such studies, but have not been systematically studied. Resting-state functional MRI was analyzed in 25 patients with TLE using graph theory analysis. Patients were divided into two groups based on anti-epileptic medication use: those taking carbamazepine/oxcarbazepine (CBZ/OXC) (n=9) and those not taking CBZ/OXC (n=16) as a part of their medication regimen. The following graph topology metrics were analyzed: global efficiency, betweenness centrality (BC), clustering coefficient, and small-world index. Multiple linear regression was used to examine the association of CBZ/OXC with graph topology. The two groups did not differ from each other based on epilepsy characteristics. Use of CBZ/OXC was associated with a lower BC. Longer epilepsy duration was also associated with a lower BC. These findings can inform graph theory-based studies in patients with TLE. The changes observed are discussed in relation to the anti-epileptic mechanism of action and adverse effects of CBZ/OXC. PMID:25492633

Segmentation of the thalamus based on BOLD frequencies affected in temporal lobe epilepsy.

PubMed

Morgan, Victoria L; Rogers, Baxter P; Abou-Khalil, Bassel

2015-11-01

Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula, and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range. Resting-state functional magnetic resonance imaging (fMRI) was acquired from 20 patients with unilateral temporal lobe epilepsy (TLE; 14 right and 6 left) and 20 healthy controls who were each age and gender matched to a specific patient. Wavelet-based fMRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject. Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067-0.013 Hz and 0.024-0.032 Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032 Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE. This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Analytic information processing style in epilepsy patients.

PubMed

Buonfiglio, Marzia; Di Sabato, Francesco; Mandillo, Silvia; Albini, Mariarita; Di Bonaventura, Carlo; Giallonardo, Annateresa; Avanzini, Giuliano

2017-08-01

Relevant to the study of epileptogenesis is learning processing, given the pivotal role that neuroplasticity assumes in both mechanisms. Recently, evoked potential analyses showed a link between analytic cognitive style and altered neural excitability in both migraine and healthy subjects, regardless of cognitive impairment or psychological disorders. In this study we evaluated analytic/global and visual/auditory perceptual dimensions of cognitive style in patients with epilepsy. Twenty-five cryptogenic temporal lobe epilepsy (TLE) patients matched with 25 idiopathic generalized epilepsy (IGE) sufferers and 25 healthy volunteers were recruited and participated in three cognitive style tests: "Sternberg-Wagner Self-Assessment Inventory", the C. Cornoldi test series called AMOS, and the Mariani Learning style Questionnaire. Our results demonstrate a significant association between analytic cognitive style and both IGE and TLE and respectively a predominant auditory and visual analytic style (ANOVA: p values <0,0001). These findings should encourage further research to investigate information processing style and its neurophysiological correlates in epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

MEG Coherence and DTI Connectivity in mTLE

PubMed Central

Nazem-Zadeh, Mohammad-Reza; Bowyer, Susan M.; Moran, John E.; Davoodi-Bojd, Esmaeil; Zillgitt, Andrew; Weiland, Barbara J.; Bagher-Ebadian, Hassan; Mahmoudi, Fariborz; Elisevich, Kost; Soltanian-Zadeh, Hamid

2017-01-01

Purpose Magnetoencephalography (MEG) is a noninvasive imaging method for localization of focal epileptiform activity in patients with epilepsy. Diffusion tensor imaging (DTI) is a noninvasive imaging method for measuring the diffusion properties of the underlying white matter tracts through which epileptiform activity is propagated. This study investigates the relationship between the cerebral functional abnormalities quantified by MEG coherence and structural abnormalities quantified by DTI in mesial temporal lobe epilepsy (mTLE). Methods Resting state MEG data was analyzed using MEG coherence source imaging (MEG-CSI) method to determine the coherence in 54 anatomical sites in 17 adult mTLE patients with surgical resection and Engel class I outcome, and 17 age- and gender- matched controls. DTI tractography identified the fiber tracts passing through these same anatomical sites of the same subjects. Then, DTI nodal degree and laterality index were calculated and compared with the corresponding MEG coherence and laterality index. Results MEG coherence laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in insular cortex and both lateral orbitofrontal and superior temporal gyri (p<0.017). Likewise, DTI nodal degree laterality, after Bonferroni adjustment, showed significant differences for right versus left mTLE in gyrus rectus, insular cortex, precuneus and superior temporal gyrus (p<0.017). In insular cortex, MEG coherence laterality correlated with DTI nodal degree laterality (R2 = 0.46; p = 0.003) in the cases of mTLE. None of these anatomical sites showed statistically significant differences in coherence laterality between right and left sides of the controls. Coherence laterality was in agreement with the declared side of epileptogenicity in insular cortex (in 82% of patients) and both lateral orbitofrontal (88%) and superior temporal gyri (88%). Nodal degree laterality was also in agreement with the declared side of epileptogenicity in gyrus rectus (in 88% of patients), insular cortex (71%), precuneus (82%) and superior temporal gyrus (94%). Combining all significant laterality indices improved the lateralization accuracy to 94% and 100% for the coherence and nodal degree laterality indices, respectively. Conclusion The associated variations in diffusion properties of fiber tracts quantified by DTI and coherence measures quantified by MEG with respect to epileptogenicity possibly reflect the chronic microstructural cerebral changes associated with functional interictal activity. The proposed methodology for using MEG and DTI to investigate diffusion abnormalities related to focal epileptogenicity and propagation may provide a further means of noninvasive lateralization. PMID:27060092

Role of Frontotemporal Fiber Tract Integrity in Task-Switching Performance of Healthy Controls and Patients with Temporal Lobe Epilepsy

PubMed Central

Kucukboyaci, N. Erkut; Girard, H.M.; Hagler, D.J.; Kuperman, J.; Tecoma, E.S.; Iragui, V.J.; Halgren, E.; McDonald, C.R.

2012-01-01

The objective of this study is to investigate the relationships among frontotemporal fiber tract compromise and task-switching performance in healthy controls and patients with temporal lobe epilepsy (TLE). We performed diffusion tensor imaging (DTI) on 30 controls and 32 patients with TLE (15 left TLE). Fractional anisotropy (FA) was calculated for four fiber tracts [uncinate fasciculus (UncF), arcuate fasciculus (ArcF), dorsal cingulum (CING), and inferior fronto-occipital fasciculus (IFOF)]. Participants completed the Trail Making Test-B (TMT-B) and Verbal Fluency Category Switching (VFCS) test. Multivariate analyses of variances (MANOVAs) were performed to investigate group differences in fiber FA and set-shifting performances. Canonical correlations were used to examine the overall patterns of structural-cognitive relationships and were followed by within-group bivariate correlations. We found a significant canonical correlation between fiber FA and task-switching performance. In controls, TMT-B correlated with left IFOF, whereas VFCS correlated with FA of left ArcF and left UncF. These correlations were not significant in patients with TLE. We report significant correlations between frontotemporal fiber tract integrity and set-shifting performance in healthy controls that appear to be absent or attenuated in patients with TLE. These findings suggest a breakdown of typical structure-function relationships in TLE that may reflect aberrant developmental or degenerative processes. PMID:22014246

Segmentation of the Thalamus Based on BOLD Frequencies Affected in Temporal Lobe Epilepsy

PubMed Central

Morgan, Victoria L.; Rogers, Baxter P.; Abou-Khalil, Bassel

2015-01-01

Objective Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range. Methods Resting-state functional MRI (fMRI) was acquired from twenty unilateral TLE (14 right, 6 left) patients and twenty healthy controls who were each age and gender matched to a specific patient. Wavelet based functional MRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject. Results Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067–0.013 Hz and 0.024–0.032 Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032 Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE. Significance This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation. PMID:26360535

MRI-negative PET-positive temporal lobe epilepsy: a distinct surgically remediable syndrome.

PubMed

Carne, R P; O'Brien, T J; Kilpatrick, C J; MacGregor, L R; Hicks, R J; Murphy, M A; Bowden, S C; Kaye, A H; Cook, M J

2004-10-01

Most patients with non-lesional temporal lobe epilepsy (NLTLE) will have the findings of hippocampal sclerosis (HS) on a high resolution MRI. However, a significant minority of patients with NLTLE and electroclinically well-lateralized temporal lobe seizures have no evidence of HS on MRI. Many of these patients have concordant hypometabolism on fluorodeoxyglucose-PET ([18F]FDG-PET). The pathophysiological basis of this latter group remains uncertain. We aimed to determine whether NLTLE without HS on MRI represents a variant of or a different clinicopathological syndrome from that of NLTLE with HS on MRI. The clinical, EEG, [18F]FDG-PET, histopathological and surgical outcomes of 30 consecutive NLTLE patients with well-lateralized EEG but without HS on MRI (HS-ve TLE) were compared with 30 consecutive age- and sex-matched NLTLE patients with well-lateralized EEG with HS on MRI (HS+ve TLE). Both the HS+ve TLE group and the HS-ve TLE patients had a high degree of [18F]FDG-PET concordant lateralization (26 out of 30 HS-ve TLE versus 27 out of 27 HS+ve TLE). HS-ve TLE patients had more widespread hypometabolism on [18F]FDG-PET by blinded visual analysis [odds ratio (OR = + infinity (2.51, -), P = 0.001]. The HS-ve TLE group less frequently had a history of febrile convulsions [OR = 0.077 (0.002-0.512), P = 0.002], more commonly had a delta rhythm at ictal onset [OR = 3.67 (0.97-20.47), P = 0.057], and less frequently had histopathological evidence of HS [OR = 0 (0-0.85), P = 0.031]. There was no significant difference in surgical outcome despite half of those without HS having a hippocampal-sparing procedure. Based on the findings outlined, HS-ve PET-positive TLE may be a surgically remediable syndrome distinct from HS+ve TLE, with a pathophysiological basis that primarily involves lateral temporal neocortical rather than mesial temporal structures.

Classification and Lateralization of Temporal Lobe Epilepsies with and without Hippocampal Atrophy Based on Whole-Brain Automatic MRI Segmentation

PubMed Central

Keihaninejad, Shiva; Heckemann, Rolf A.; Gousias, Ioannis S.; Hajnal, Joseph V.; Duncan, John S.; Aljabar, Paul; Rueckert, Daniel; Hammers, Alexander

2012-01-01

Brain images contain information suitable for automatically sorting subjects into categories such as healthy controls and patients. We sought to identify morphometric criteria for distinguishing controls (n = 28) from patients with unilateral temporal lobe epilepsy (TLE), 60 with and 20 without hippocampal atrophy (TLE-HA and TLE-N, respectively), and for determining the presumed side of seizure onset. The framework employs multi-atlas segmentation to estimate the volumes of 83 brain structures. A kernel-based separability criterion was then used to identify structures whose volumes discriminate between the groups. Next, we applied support vector machines (SVM) to the selected set for classification on the basis of volumes. We also computed pairwise similarities between all subjects and used spectral analysis to convert these into per-subject features. SVM was again applied to these feature data. After training on a subgroup, all TLE-HA patients were correctly distinguished from controls, achieving an accuracy of 96 ± 2% in both classification schemes. For TLE-N patients, the accuracy was 86 ± 2% based on structural volumes and 91 ± 3% using spectral analysis. Structures discriminating between patients and controls were mainly localized ipsilaterally to the presumed seizure focus. For the TLE-HA group, they were mainly in the temporal lobe; for the TLE-N group they included orbitofrontal regions, as well as the ipsilateral substantia nigra. Correct lateralization of the presumed seizure onset zone was achieved using hippocampi and parahippocampal gyri in all TLE-HA patients using either classification scheme; in the TLE-N patients, lateralization was accurate based on structural volumes in 86 ± 4%, and in 94 ± 4% with the spectral analysis approach. Unilateral TLE has imaging features that can be identified automatically, even when they are invisible to human experts. Such morphometric image features may serve as classification and lateralization criteria. The technique also detects unsuspected distinguishing features like the substantia nigra, warranting further study. PMID:22523539

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2014-09-01

NOTES 14. ABSTRACT Traumatic Brain Injury (TBI) is a well-established inducer of temporal lobe epilepsy (TLE), a frequently medically intractable... epilepsy syndrome. The controlled cortical impact (CCI) model of posttraumatic epilepsy in mice is a well established animal model of TBI that results...reduce development of post-traumatic epilepsy , and did not significantly improve memory function, but did enhance the motor recovery. These findings

Network-Level Analysis of Cortical Thickness of the Epileptic Brain

PubMed Central

Raj, A; Mueller, S.G; Young, K; Laxer, K.D.; Weiner, M

2010-01-01

Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe is the most common form of focal epilepsy. However, the seizures are not confined to the temporal lobe but can spread to other, anatomically connected brain regions where they can cause similar structural abnormalities as observed in the focus. The aim of this study was to derive whole brain networks from volumetric data and obtain network-centric measures which can capture cortical thinning characteristic for TLE and can be used for classifying a given MRI into TLE or normal, and to obtain additional summary statistics which relate to the extent and spread of the disease. T1 weighted whole brain images were acquired on a 4T magnet in 13 patients with TLE with mesial temporal lobe sclerosis (TLE-MTS), 14 patients with TLE with normal MRI (TLE-no) and 30 controls. Mean cortical thickness and curvature measurements were obtained using the Freesurfer software. These values were used to derive a graph, or network, for each subject. The nodes of the graph are brain regions, and edges represent disease progression paths. We show how to obtain summary statistics like mean, median and variance defined for these networks and to perform exploratory analyses like correlation and classification. Our results indicate that the proposed network approach can improve accuracy of classifying subjects into 2 groups (control and TLE), from 78% for non-network classifiers to 93% using the proposed approach. We also obtain network “peakiness” values using statistical measures like entropy and complexity - this appears to be a good characterizer of the disease, and may have utility in surgical planning. PMID:20553893

Epileptic Hypergraphia: The Impact of Prolific Writing on Language Creativity

ERIC Educational Resources Information Center

Ammari, Elham H.

2012-01-01

Catalyzed academic concerns have been shown so far to tackle the issue of temporal lobe epileptic hypergraphia and the extent of its creativity. Temporal lobe epilepsy hence, (TLE) as a neurological brain disorder, has captured the attention of concerned scholars ever since. A constellation of TLE and its cohorts have baffled scientists,…

The long-term course of temporal lobe epilepsy: From unilateral to bilateral interictal epileptiform discharges in repeated video-EEG monitorings.

PubMed

Gollwitzer, Stephanie; Scott, Catherine A; Farrell, Fiona; Bell, Gail S; de Tisi, Jane; Walker, Matthew C; Wehner, Tim; Sander, Josemir W; Hamer, Hajo M; Diehl, Beate

2017-03-01

Bilateral interictal epileptiform discharges (IED) and ictal patterns are common in temporal lobe epilepsy (TLE) and have been associated with decreased chances of seizure freedom after epilepsy surgery. It is unclear whether secondary epileptogenesis, although demonstrated in experimental models, exists in humans and may account for progression of epilepsy. We reviewed consecutive video-EEG recordings from 1992 to 2014 repeated at least two years apart (mean interval 6.14years) in 100 people diagnosed with TLE. Ictal EEG patterns and IED remained restricted to one hemisphere in 36 people (group 1), 46 exhibited bilateral abnormalities from the first recording (group 2), 18 progressed from unilateral to bilateral EEG pathology over time (group 3). No significant differences between the three groups were seen with respect to age at epilepsy onset, duration, or underlying pathology. Extra-temporal IED during the first EEG recording were associated with an increased risk of developing bilateral epileptiform changes over time (hazard ratio 3.67; 95% CI 1.4, 9.4). Our findings provide some support of progression in TLE and raise the possibility of secondary epileptogenesis in humans. The development of an independent contra-lateral epileptogenic focus is known to be associated with a less favorable surgical outcome. We defined reliable EEG markers for an increased risk of progression to more widespread or independent bitemporal epileptogenicity at an early stage, thus allowing for individualized pre-surgical counselling. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional imaging of semantic memory predicts postoperative episodic memory functions in chronic temporal lobe epilepsy.

PubMed

Köylü, Bülent; Walser, Gerald; Ischebeck, Anja; Ortler, Martin; Benke, Thomas

2008-08-05

Medial temporal (MTL) structures have crucial functions in episodic (EM), but also in semantic memory (SM) processing. Preoperative functional magnetic resonance imaging (fMRI) activity within the MTL is increasingly used to predict post-surgical memory capacities. Based on the hypothesis that EM and SM memory functions are both hosted by the MTL the present study wanted to explore the relationship between SM related activations in the MTL as assessed before and the capacity of EM functions after surgery. Patients with chronic unilateral left (n=14) and right (n=12) temporal lobe epilepsy (TLE) performed a standard word list learning test pre- and postoperatively, and a fMRI procedure before the operation using a semantic decision task. SM processing caused significant bilateral MTL activations in both patient groups. While right TLE patients showed asymmetry of fMRI activation with more activation in the left MTL, left TLE patients had almost equal activation in both MTL regions. Contrasting left TLE versus right TLE patients revealed greater activity within the right MTL, whereas no significant difference was observed for the reverse contrast. Greater effect size in the MTL region ipsilateral to the seizure focus was significantly and positively correlated with preoperative EM abilities. Greater effect size in the contralateral MTL was correlated with better postoperative verbal EM, especially in left TLE patients. These results suggest that functional imaging of SM tasks may be useful to predict postoperative verbal memory in TLE. They also advocate a common neuroanatomical basis for SM and EM processes in the MTL.

Levetiracetam reduces abnormal network activations in temporal lobe epilepsy.

PubMed

Wandschneider, Britta; Stretton, Jason; Sidhu, Meneka; Centeno, Maria; Kozák, Lajos R; Symms, Mark; Thompson, Pamela J; Duncan, John S; Koepp, Matthias J

2014-10-21

We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures. © 2014 American Academy of Neurology.

Presurgery resting-state local graph-theory measures predict neurocognitive outcomes after brain surgery in temporal lobe epilepsy.

PubMed

Doucet, Gaelle E; Rider, Robert; Taylor, Nathan; Skidmore, Christopher; Sharan, Ashwini; Sperling, Michael; Tracy, Joseph I

2015-04-01

This study determined the ability of resting-state functional connectivity (rsFC) graph-theory measures to predict neurocognitive status postsurgery in patients with temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy (ATL). A presurgical resting-state functional magnetic resonance imaging (fMRI) condition was collected in 16 left and 16 right TLE patients who underwent ATL. In addition, patients received neuropsychological testing pre- and postsurgery in verbal and nonverbal episodic memory, language, working memory, and attention domains. Regarding the functional data, we investigated three graph-theory properties (local efficiency, distance, and participation), measuring segregation, integration and centrality, respectively. These measures were only computed in regions of functional relevance to the ictal pathology, or the cognitive domain. Linear regression analyses were computed to predict the change in each neurocognitive domain. Our analyses revealed that cognitive outcome was successfully predicted with at least 68% of the variance explained in each model, for both TLE groups. The only model not significantly predictive involved nonverbal episodic memory outcome in right TLE. Measures involving the healthy hippocampus were the most common among the predictors, suggesting that enhanced integration of this structure with the rest of the brain may improve cognitive outcomes. Regardless of TLE group, left inferior frontal regions were the best predictors of language outcome. Working memory outcome was predicted mostly by right-sided regions, in both groups. Overall, the results indicated our integration measure was the most predictive of neurocognitive outcome. In contrast, our segregation measure was the least predictive. This study provides evidence that presurgery rsFC measures may help determine neurocognitive outcomes following ATL. The results have implications for refining our understanding of compensatory reorganization and predicting cognitive outcome after ATL. The results are encouraging with regard to the clinical relevance of using graph-theory measures in presurgical algorithms in the setting of TLE. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy.

PubMed

Witt, Juri-Alexander; Coras, Roland; Schramm, Johannes; Becker, Albert J; Elger, Christian E; Blümcke, Ingmar; Helmstaedter, Christoph

2014-04-01

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33-0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50-0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus - rather than a specific subfield pathology - is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. Copyright © 2013 Wiley Periodicals, Inc.

Recognition of emotion with temporal lobe epilepsy and asymmetrical amygdala damage.

PubMed

Fowler, Helen L; Baker, Gus A; Tipples, Jason; Hare, Dougal J; Keller, Simon; Chadwick, David W; Young, Andrew W

2006-08-01

Impairments in emotion recognition occur when there is bilateral damage to the amygdala. In this study, ability to recognize auditory and visual expressions of emotion was investigated in people with asymmetrical amygdala damage (AAD) and temporal lobe epilepsy (TLE). Recognition of five emotions was tested across three participant groups: those with right AAD and TLE, those with left AAD and TLE, and a comparison group. Four tasks were administered: recognition of emotion from facial expressions, sentences describing emotion-laden situations, nonverbal sounds, and prosody. Accuracy scores for each task and emotion were analysed, and no consistent overall effect of AAD on emotion recognition was found. However, some individual participants with AAD were significantly impaired at recognizing emotions, in both auditory and visual domains. The findings indicate that a minority of individuals with AAD have impairments in emotion recognition, but no evidence of specific impairments (e.g., visual or auditory) was found.

Network Alterations Supporting Word Retrieval in Patients with Medial Temporal Lobe Epilepsy

ERIC Educational Resources Information Center

Protzner, Andrea B.; McAndrews, Mary Pat

2011-01-01

Although the hippocampus is not considered a key structure in semantic memory, patients with medial-temporal lobe epilepsy (mTLE) have deficits in semantic access on some word retrieval tasks. We hypothesized that these deficits reflect the negative impact of focal epilepsy on remote cerebral structures. Thus, we expected that the networks that…

Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity.

PubMed

Keller, Simon S; O'Muircheartaigh, Jonathan; Traynor, Catherine; Towgood, Karren; Barker, Gareth J; Richardson, Mark P

2014-02-01

Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. For 23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Clinical utility of the Wechsler Memory Scale - Fourth Edition (WMS-IV) in patients with intractable temporal lobe epilepsy.

PubMed

Bouman, Zita; Elhorst, Didi; Hendriks, Marc P H; Kessels, Roy P C; Aldenkamp, Albert P

2016-02-01

The Wechsler Memory Scale (WMS) is one of the most widely used test batteries to assess memory functions in patients with brain dysfunctions of different etiologies. This study examined the clinical validation of the Dutch Wechsler Memory Scale - Fourth Edition (WMS-IV-NL) in patients with temporal lobe epilepsy (TLE). The sample consisted of 75 patients with intractable TLE, who were eligible for epilepsy surgery, and 77 demographically matched healthy controls. All participants were examined with the WMS-IV-NL. Patients with TLE performed significantly worse than healthy controls on all WMS-IV-NL indices and subtests (p<.01), with the exception of the Visual Working Memory Index including its contributing subtests, as well as the subtests Logical Memory I, Verbal Paired Associates I, and Designs II. In addition, patients with mesiotemporal abnormalities performed significantly worse than patients with lateral temporal abnormalities on the subtests Logical Memory I and Designs II and all the indices (p<.05), with the exception of the Auditory Memory Index and Visual Working Memory Index. Patients with either a left or a right temporal focus performed equally on all WMS-IV-NL indices and subtests (F(15, 50)=.70, p=.78), as well as the Auditory-Visual discrepancy score (t(64)=-1.40, p=.17). The WMS-IV-NL is capable of detecting memory problems in patients with TLE, indicating that it is a sufficiently valid memory battery. Furthermore, the findings support previous research showing that the WMS-IV has limited value in identifying material-specific memory deficits in presurgical patients with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery.

PubMed

Casciato, Sara; Picardi, Angelo; D'Aniello, Alfredo; De Risi, Marco; Grillea, Giovanni; Quarato, Pier Paolo; Mascia, Addolorata; Grammaldo, Liliana G; Meldolesi, Giulio Nicolo'; Morace, Roberta; Esposito, Vincenzo; Di Gennaro, Giancarlo

2017-05-01

To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery. We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome. TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p<.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications. High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence seizure outcome. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neuropsychological deficits in temporal lobe epilepsy: A comprehensive review

PubMed Central

Zhao, Fengqing; Kang, Hai; You, LIbo; Rastogi, Priyanka; Venkatesh, D.; Chandra, Mina

2014-01-01

Temporal lobe epilepsy (TLE) is the most prevalent form of complex partial seizures with temporal lobe origin of electrical abnormality. Studies have shown that recurrent seizures affect all aspects of cognitive functioning, including memory, language, praxis, executive functions, and social judgment, among several others. In this article, we will review these cognitive impairments along with their neuropathological correlates in a comprehensive manner. We will see that neuropsychological deficits are prevalent in TLE. Much of the effort has been laid on memory due to the notion that temporal lobe brain structures involved in TLE play a central role in consolidating information into memory. It seems that damage to the mesial structure of the temporal lobe, particularly the amygdale and hippocampus, has the main role in these memory difficulties and the neurobiological plausibility of the role of the temporal lobe in different aspects of memory. Here, we will cover the sub-domains of working memory and episodic memory deficits. This is we will further proceed to evaluate the evidences of executive function deficits in TLE and will see that set-shifting among other EFs is specifically affected in TLE as is social cognition. Finally, critical components of language related deficits are also found in the form of word-finding difficulties. To conclude, TLE affects several of cognitive function domains, but the etiopathogenesis of all these dysfunctions remain elusive. Further well-designed studies are needed for a better understanding of these disorders. PMID:25506156

Impaired extinction of fear and maintained amygdala-hippocampal theta synchrony in a mouse model of temporal lobe epilepsy.

PubMed

Lesting, Jörg; Geiger, Matthias; Narayanan, Rajeevan T; Pape, Hans-Christian; Seidenbecher, Thomas

2011-02-01

The relationship between epilepsy and fear has received much attention. However, seizure-modulated fear and physiologic or structural correlates have not been examined systematically, and the underlying basics of network levels remain unclear to date. Therefore, this project was set up to characterize the neurophysiologic basis of seizure-related fear and the contribution of the amygdala-hippocampus system. The experimental strategy was composed of the following steps: (1) use of the mouse pilocarpine model of temporal lobe epilepsy (TLE); (2) behavioral analyses of anxiety states in the elevated plus maze test, light-dark avoidance test, and Pavlovian fear conditioning; and (3) probing neurophysiologic activity patterns in amygdala-hippocampal circuits in freely behaving mice. Our results displayed no significant differences in basic anxiety levels comparing mice that developed spontaneous recurrent seizures (SRS) and controls. Furthermore, conditioned fear memory retrieval was not influenced in SRS mice. However, during fear memory extinction, SRS mice showed an extended freezing behavior and a maintained amygdala-hippocampal theta frequency synchronization compared to controls. These results indicate specific alterations in conditioned fear behavior and related neurophysiologic activities in the amygdala-hippocampal network contributing to impaired fear memory extinction in mice with TLE. Clinically, the nonextinguished fear memories may well contribute to the experience of fear in patients with TLE. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

The presence of polyglucosan bodies in temporal lobe epilepsy: its role and significance.

PubMed

Abubakr, Abuhuziefa; Wambacq, Ilse; Donahue, John E; Zappulla, Rosario

2005-11-01

Mesial temporal sclerosis (MTS) is an important pathology in temporal lobe epilepsy (TLE) and often associated with good surgical outcome, however prognostic factors for surgical outcome are conflicting. The authors examine seizure outcome after surgery for TLE due to MTS, with focus on the presence of polyglucosan bodies (PGBs), and its relation to the epileptogenic process. Records of 44 consecutive patients with intractable TLE who underwent anterior temporal lobectomy (ATL) at JFK medical center between 1994-2001 were reviewed. Details of clinical, electrophysiological evaluation, and outcome were collected. All slides were reviewed for the presence of MTS. In twenty-one patients with MTS, detailed histology of surgical specimens was reviewed and relative concentration of PGBs was assessed. The postoperative follow-up duration ranges between 28-74 months. Surgical outcome was evaluated according to Engel's classification. Data of fourteen females (mean age 32.8 years) and 7 males (mean age 34.2) were analyzed. PBGs were identified in 10 patients (8 females and 2 males). All 10 patients had good surgical outcome, with 6 patients (60%) being seizure free (class 1) and 4 patients as class 2. While 11 patients (6 males and 5 females) with absent PGB, 72.8% had good surgical outcome. Of these, 7 (63.8%) had class 1, 1 patient had class 2, and 3 patients had class 3&4. Assessing several risk factors, the only significant difference between the two groups was epilepsy duration, which was significantly longer in patients with PGBs (P = 0.011). The histological presence of PGB is associated with long duration of epilepsy and could be the consequence of epilepsy. Despite prolonged duration of epilepsy, the surgical outcome in PGBs +ve is similar to PGBs -ve patients.

Hush sign: a new clinical sign in temporal lobe epilepsy.

PubMed

Kutlu, Gulnihal; Bilir, Erhan; Erdem, Atilla; Gomceli, Yasemin B; Kurt, G Semiha; Serdaroglu, Ayse

2005-05-01

Neurologists have been analyzing the clinical behaviors that occur during seizures for many years. Several ictal behaviors have been defined in temporal lobe epilepsy (TLE). Ictal behaviors are especially important in the evaluation of epilepsy surgery candidates. We propose a new lateralizing sign in TLE originating from the nondominant hemisphere-the "hush" sign. Our patients were 30- and 21-year old women (Cases 1 and 2, respectively). Their epileptogenic foci were localized to the right mesial temporal region after noninvasive presurgical investigations. Case 1 had no cranial MRI abnormality, whereas cranial MRI revealed right hippocampal atrophy in Case 2. These women repeatedly moved their right index fingers to their mouth while puckering their lips during complex partial seizures. We have named this ictal behavior the "hush" sign. Anterior temporal lobectomy with amygdalohippocampectomy was performed in both patients, and pathological examinations revealed hippocampal sclerosis. The "hush" sign no longer occurred after seizures were controlled. They were seizure free as of 30 and 31 months of follow-up, respectively. We believe that the "hush" sign may be supportive of a diagnosis of TLE originating from the nondominant hemisphere. This sign may occur as a result of ictal activation of a specific brain region in this hemisphere.

Temporal plus epilepsy: Anatomo-electroclinical subtypes

PubMed Central

Andrade-Machado, René; Benjumea-Cuartas, Vanessa

2016-01-01

Background: Mesial temporal lobe epilepsy (TLE) is a remediable epileptic syndrome. About 40% of patients continue to have seizures after standard temporal lobectomy. It has been suggested that some of these patients could actually suffer from a more complex epileptogenic network. Because a few papers have been dedicated to this topic, we decided to write an article updating this theme. Methods: We performed a literature search using the following terminology: “temporal plus epilepsy and networks,” “temporal plus epilepsy,” “orbito-temporal epilepsy,” “temporo-insular epilepsy,” “temporo-parieto-occipital (TPO) epilepsy,” “parieto-temporal epilepsy,” “intracortical evoked potential and temporal plus epilepsy,” “temporal lobe connectivity and epilepsy,” “intracortical evoked potential and epilepsy surgery,” “role of extratemporal structures in TLE,” “surgical failure after temporal lobectomy,” “Diffusion tensor imaging (DTI) and temporal epilepsy,” and “positron emission tomography (PET) in temporal plus lobe epilepsy” in the existing PubMed databases. We searched only English and Spanish literature. Only papers that fit with the above-mentioned descriptors were included as part of the evidence. Other articles were used to reference some aspects of the temporal plus epilepsy. Results: A total of 48 papers from 2334 were revised. The most frequently reported auras in these groups of patients are gustatory hallucinations, vestibular illusions, laryngeal and throat constriction, atypical distribution of somatosensory symptoms (perioral and hands, bilaterally hands paresthesias, trunk and other). The most common signs are tonic posturing, hemifacial twist, and frequent bilateral clonic movements. Interictal electroencephalographic (EEG) patterns exhibit regional and frequently bilateral spikes and/or slow waves. The first ictal electrographic change is mostly regional. It is important to note that the evidence is supported by case series or case reports. Thus, most of the data presented could represent the features on these cases and not actually the totality of the iceberg. Conclusion: Temporal plus epilepsy is a diagnosis that can be done only after the invasive recordings have been analyzed but an adequate suspicion may arise based on clinical, EEG and imaging data. PMID:27648177

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2015-06-01

transforms into one that sustains seizures. It is instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury...Surprisingly, the combination attenuates seizures in two different models of temporal lobe epilepsy. 15. SUBJECT TERMS Status Epilepticus , Wnt...will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of temporal lobe epilepsy (TLE), a disease

Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis.

PubMed

Mueller, Susanne G; Ebel, Andreas; Barakos, Jerome; Scanlon, Cathy; Cheong, Ian; Finlay, Daniel; Garcia, Paul; Weiner, Michael W; Laxer, Kenneth D

2011-04-01

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr+Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr+Cho) reductions. NAA/(Cr+Cho) reductions had a bilateral fronto-temporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr+Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr+Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE.

Excessive masturbation after epilepsy surgery.

PubMed

Ozmen, Mine; Erdogan, Ayten; Duvenci, Sirin; Ozyurt, Emin; Ozkara, Cigdem

2004-02-01

Sexual behavior changes as well as depression, anxiety, and organic mood/personality disorders have been reported in temporal lobe epilepsy (TLE) patients before and after epilepsy surgery. The authors describe a 14-year-old girl with symptoms of excessive masturbation in inappropriate places, social withdrawal, irritability, aggressive behavior, and crying spells after selective amygdalohippocampectomy for medically intractable TLE with hippocampal sclerosis. Since the family members felt extremely embarrassed, they were upset and angry with the patient which, in turn, increased her depressive symptoms. Both her excessive masturbation behavior and depressive symptoms remitted within 2 months of psychoeducative intervention and treatment with citalopram 20mg/day. Excessive masturbation is proposed to be related to the psychosocial changes due to seizure-free status after surgery as well as other possible mechanisms such as Kluver-Bucy syndrome features and neurophysiologic changes associated with the cessation of epileptic discharges. This case demonstrates that psychiatric problems and sexual changes encountered after epilepsy surgery are possibly multifactorial and in adolescence hypersexuality may be manifested as excessive masturbation behavior.

Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.

PubMed

Althaus, A L; Sagher, O; Parent, J M; Murphy, G G

2015-02-15

Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. Copyright © 2015 the American Physiological Society.

Temporal lobe epilepsy and affective disorders: the role of the subgenual anterior cingulate cortex.

PubMed

Stretton, J; Pope, R A; Winston, G P; Sidhu, M K; Symms, M; Duncan, J S; Koepp, M; Thompson, P J; Foong, J

2015-02-01

Reduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present in temporal lobe epilepsy (TLE) patients with a history of affective psychopathology. 17 TLE patients with a lifetime affective diagnosis, 31 TLE patients with no formal psychiatric history and 30 HVs were included. We used a visuo-spatial 'n-back' paradigm to compare working memory (WM) network activation between these groups. Post hoc analyses included voxel-based morphometry and diffusion tensor imaging. The Beck Depression Inventory-Fast Screen and Beck Anxiety Inventory were completed on the day of scanning. Each group activated the fronto-parietal WM networks and deactivated the typical DMN in response to increasing task demands. Group comparison revealed that TLE patients with lifetime affective morbidity showed significantly greater deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE-only or the HVs (p<0.001). This effect persisted after covarying for current psychotropic medication and severity of current depressive/anxiety symptoms (all p<0.001). Correlational analysis revealed that this finding was not driven by differences in task performance. There were no significant differences in grey matter volume or structural connectivity between the TLE groups. Our results provide novel evidence suggesting that affective psychopathology in TLE has a neurobiological correlate, and in this context the sACC performs differently compared with network activity in primary affective disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Contribution of amygdala pathology to comorbid emotional disturbances in temporal lobe epilepsy.

PubMed

Yilmazer-Hanke, Deniz; O'Loughlin, Elaine; McDermott, Kieran

2016-06-01

The amygdala contributes to the generation and propagation of epileptiform activity in temporal lobe epilepsy (TLE). Ictal symptoms such as fear, dreamy states (déjà vu, memory flashbacks, experiential hallucinations), epigastric auras, or sympathetic outflow with cardiovascular changes are often linked to a seizure focus in the amygdala. However, the amygdala may also play a role in comorbid anxiety, depression, and other psychiatric symptoms experienced in the interictal phase, especially in pharmacoresistant TLE. The few studies available on TLE-related alterations in surgical amygdala specimens indicate loss of both excitatory spiny projection neurons as well as interneurons in nuclei with a cortex-like architecture, which may influence mechanisms of feedforward and feedback inhibition. Studies of the human amygdala indicate global alterations in the density of AMPA/kainate, metabotropic glutamate, γ-aminobutyric acid type A (GABAA ), muscarinic M2 and M3, serotonergic 5-HT1A, and adrenergic α1 receptors. Also, amygdala GABAergic and neuropeptide Y (NPY) systems affected in human TLE are both involved in antiepileptic and anxiolytic effects. Experimental and human positron emission tomography studies indicate changes in amygdala serotonergic, NPY Y1 receptor, neurokinin, and opioid systems in emotional disturbances in TLE. Of particular interest is the reduction in amygdala volume in conjunction with ictal fear, seizure focus in the amygdala, and amygdala and hippocampal sclerosis in TLE patients. In contrast, patients with interictal depression often have an intact or even enlarged amygdala and a negative MRI associated with amygdala hypometabolism, which can be associated with limbic autoimmune encephalitis. These findings suggest a differential role of TLE-related amygdala changes in ictal and interictal emotional disturbances. © 2015 Wiley Periodicals, Inc.

GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA “phasic” receptors

PubMed Central

Palma, Eleonora; Roseti, Cristina; Maiolino, Francesca; Fucile, Sergio; Martinello, Katiuscia; Mazzuferi, Manuela; Aronica, Eleonora; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Miledi, Ricardo; Simonato, Michele; Eusebi, Fabrizio

2007-01-01

A study was made of the “rundown” of GABAA receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABAA receptors. Upon repetitive activation with GABA (1 mM), “epileptic” GABAA receptors exhibited a GABAA-current (IGABA) rundown that was significantly enhanced by Zn2+ (≤250 μM), and practically abolished by the high-affinity GABAA receptor inverse agonist SR95531 (gabazine; 2.5–25 μM). Conversely, IGABA generated by “control” GABAA receptors microtransplanted from nonepileptic temporal lobe, lesional TLE, or authoptic disease-free tissues remained stable during repetitive stimulation, even in oocytes treated with Zn2+. We conclude that rundown of mTLE epileptic receptors depends on the presence of “phasic GABAA receptors” that have low sensitivity to antagonism by Zn2+. Additionally, we found that GABAA receptors, microtransplanted from the cerebral cortex of adult rats exhibiting recurrent seizures, caused by pilocarpine-induced status epilepticus, showed greater rundown than control tissue, an event also occurring in patch-clamped rat pyramidal neurons. Rundown of epileptic rat receptors resembled that of human mTLE receptors, being enhanced by Zn2+ (40 μM) and sensitive to the antiepileptic agent levetiracetam, the neurotrophin brain-derived neurotrophic factor, and the phosphatase blocker okadaic acid. Our findings point to the rundown of GABAA receptors as a hallmark of TLE and suggest that modulating tonic and phasic mTLE GABAA receptor activity may represent a useful therapeutic approach to the disease. PMID:18083839

A hierarchical approach for online temporal lobe seizure detection in long-term intracranial EEG recordings

NASA Astrophysics Data System (ADS)

Liang, Sheng-Fu; Chen, Yi-Chun; Wang, Yu-Lin; Chen, Pin-Tzu; Yang, Chia-Hsiang; Chiueh, Herming

2013-08-01

Objective. Around 1% of the world's population is affected by epilepsy, and nearly 25% of patients cannot be treated effectively by available therapies. The presence of closed-loop seizure-triggered stimulation provides a promising solution for these patients. Realization of fast, accurate, and energy-efficient seizure detection is the key to such implants. In this study, we propose a two-stage on-line seizure detection algorithm with low-energy consumption for temporal lobe epilepsy (TLE). Approach. Multi-channel signals are processed through independent component analysis and the most representative independent component (IC) is automatically selected to eliminate artifacts. Seizure-like intracranial electroencephalogram (iEEG) segments are fast detected in the first stage of the proposed method and these seizures are confirmed in the second stage. The conditional activation of the second-stage signal processing reduces the computational effort, and hence energy, since most of the non-seizure events are filtered out in the first stage. Main results. Long-term iEEG recordings of 11 patients who suffered from TLE were analyzed via leave-one-out cross validation. The proposed method has a detection accuracy of 95.24%, a false alarm rate of 0.09/h, and an average detection delay time of 9.2 s. For the six patients with mesial TLE, a detection accuracy of 100.0%, a false alarm rate of 0.06/h, and an average detection delay time of 4.8 s can be achieved. The hierarchical approach provides a 90% energy reduction, yielding effective and energy-efficient implementation for real-time epileptic seizure detection. Significance. An on-line seizure detection method that can be applied to monitor continuous iEEG signals of patients who suffered from TLE was developed. An IC selection strategy to automatically determine the most seizure-related IC for seizure detection was also proposed. The system has advantages of (1) high detection accuracy, (2) low false alarm, (3) short detection latency, and (4) energy-efficient design for hardware implementation.

Detection of whole-brain abnormalities in temporal lobe epilepsy using tensor-based morphometry with DARTEL

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Lv, Bin; Li, Meng; Jin, Zhengyu

2009-10-01

Tensor-based morphometry (TBM) is an automated technique for detecting the anatomical differences between populations by examining the gradients of the deformation fields used to nonlinearly warp MR images. The purpose of this study was to investigate the whole-brain volume changes between the patients with unilateral temporal lobe epilepsy (TLE) and the controls using TBM with DARTEL, which could achieve more accurate inter-subject registration of brain images. T1-weighted images were acquired from 21 left-TLE patients, 21 right-TLE patients and 21 healthy controls, which were matched in age and gender. The determinants of the gradient of deformation fields at voxel level were obtained to quantify the expansion or contraction for individual images relative to the template, and then logarithmical transformation was applied on it. A whole brain analysis was performed using general lineal model (GLM), and the multiple comparison was corrected by false discovery rate (FDR) with p<0.05. For left-TLE patients, significant volume reductions were found in hippocampus, cingulate gyrus, precentral gyrus, right temporal lobe and cerebellum. These results potentially support the utility of TBM with DARTEL to study the structural changes between groups.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

PubMed

Dinkelacker, Vera; Xin, Xu; Baulac, Michel; Samson, Séverine; Dupont, Sophie

2016-09-01

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity. Copyright © 2016. Published by Elsevier Inc.

Déjà vu in unilateral temporal-lobe epilepsy is associated with selective familiarity impairments on experimental tasks of recognition memory.

PubMed

Martin, Chris B; Mirsattari, Seyed M; Pruessner, Jens C; Pietrantonio, Sandra; Burneo, Jorge G; Hayman-Abello, Brent; Köhler, Stefan

2012-11-01

In déjà vu, a phenomenological impression of familiarity for the current visual environment is experienced with a sense that it should in fact not feel familiar. The fleeting nature of this phenomenon in daily life, and the difficulty in developing experimental paradigms to elicit it, has hindered progress in understanding déjà vu. Some neurological patients with temporal-lobe epilepsy (TLE) consistently experience déjà vu at the onset of their seizures. An investigation of such patients offers a unique opportunity to shed light on its possible underlying mechanisms. In the present study, we sought to determine whether unilateral TLE patients with déjà vu (TLE+) show a unique pattern of interictal memory deficits that selectively affect familiarity assessment. In Experiment 1, we employed a Remember-Know paradigm for categorized visual scenes and found evidence for impairments that were limited to familiarity-based responses. In Experiment 2, we administered an exclusion task for highly similar categorized visual scenes that placed both recognition processes in opposition. TLE+ patients again displayed recognition impairments, and these impairments spared their ability to engage recollective processes so as to counteract familiarity. The selective deficits we observed in TLE+ patients contrasted with the broader pattern of recognition-memory impairments that was present in a control group of unilateral patients without déjà vu (TLE-). MRI volumetry revealed that ipsilateral medial temporal structures were less broadly affected in TLE+ than in TLE- patients, with a trend for more focal volume reductions in the rhinal cortices of the TLE+ group. The current findings establish a first empirical link between déjà vu in TLE and processes of familiarity assessment, as defined and measured in current cognitive models. They also reveal a pattern of selectivity in recognition impairments that is rarely observed and, thus, of significant theoretical interest to the memory literature at large. Copyright © 2012 Elsevier Ltd. All rights reserved.

Is there a creative functional paradoxical facilitation in juvenile myoclonic epilepsy?

PubMed

Senf, Philine; Scheuren, Lena; Holtkamp, Martin

2016-09-01

In patients with juvenile myoclonic epilepsy (JME), a specific personality profile suggestive of frontal lobe dysfunctions has been described. From a neurobiological point of view, the frontal lobe seems to be crucial for creative processes, although the exact role remains unclear. The theory of creative paradoxical functional facilitation (PFF) assumes that disinhibited frontal lobe function can enhance creative abilities. The aim of the current study was to explore our hypothesis that JME is associated with higher artistic creativity based on the theory of PFF. We assessed 25 patients with JME aged 18 to 40years in regard to neuropsychological creativity testing. Results were compared with those of 25 age-, sex-, and level of education-matched healthy control subjects (HC) and patients with temporal lobe epilepsy (TLE). Creative abilities were assessed using two validated and standardized tests: 1) nonverbal: the incomplete figure task of Torrance Test of Creative Thinking and 2) verbal: verbal creativity test. Additionally, a basic assessment of fluid intelligence (test for problem solving) and frontal lobe function (trail-making test) was administered to all participants. Verbal creativity was impaired in both groups with epilepsy compared with that in HC (specific score: JME vs. HC, p=0.008; TLE vs. HC, p=0.003). In regard to nonverbal creative abilities, both groups with epilepsy exhibited fair performance. Level of fluid intelligence was even in all groups (p=0.433). Only patients with JME showed deficits in the frontal lobe test of psychomotor speed (time in seconds: 67.7 JME vs. 54.6 TLE vs. 52.8 HC; p=0.045). Overall, our study did not reveal increased creativity in JME. The current findings provide insights into creative abilities in two different epilepsy syndromes. Knowledge on specific neuropsychological strengths or deficits in patients with epilepsy may be useful for treatment or counseling. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating executive function in patients with temporal lobe epilepsy using the frontal assessment battery.

PubMed

Agah, Elmira; Asgari-Rad, Nasima; Ahmadi, Mona; Tafakhori, Abbas; Aghamollaii, Vajiheh

2017-07-01

Previous studies have demonstrated executive dysfunction in patients with temporal lobe epilepsy (TLE). Frontal assessment battery (FAB) is a short neuropsychological tool that was developed for assessment of frontal lobe function in a clinical setting. The aim of the present study is to evaluate the clinical utility of FAB for detection of executive dysfunction in TLE patients. Forty-eight TLE patients and 48 sex and age-matched healthy controls participated in this study. Compared to healthy participants, the total FAB score was significantly lower among the TLE patients. TLE patients performed significantly worse at the mental flexibility, motor programming, sensitivity to interference and inhibitory control tasks. The duration of time has been passed since the last seizure was the only significant predictor of FAB score and patients who had a seizure less than a week before the evaluation time, had significantly lower FAB scores. The number of antiepileptic drugs (AEDs) did not influence the executive function in this study; however, sodium valproate was found to affect the mental flexibility. In conclusion, impaired executive function is common in TLE patients, and we suggest that FAB is a clinically applicable tool to monitor it. Moreover, we found that the time of the last seizure is a significant predictor of executive functioning and patients' performance may become worse up to seven days after a seizure. We also recommend that clinicians evaluate the cognitive adverse effects of AEDs especially sodium valproate, which was found to affect the mental flexibility in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

The course of language functions after temporal lobe epilepsy surgery: a prospective study.

PubMed

Giovagnoli, A R; Parente, A; Didato, G; Manfredi, V; Deleo, F; Tringali, G; Villani, F

2016-12-01

Anterior temporal lobectomy (ATL) within the language-dominant hemisphere can impair naming. This prospective study examined the pre-operative to post-operative course of different language components, clarifying which changes are relevant within the short-term and long-term outcome of language. Patients with drug-resistant temporal lobe epilepsy (TLE) were evaluated using the Token, Boston Naming and Word Fluency tests assessing sentence comprehension and word-finding on visual, semantic or phonemic cues. A total of 106 patients were evaluated before and 6 months, 1 and 2 years after ATL; 60 patients were also evaluated after 5 years and 38 controls were assessed at baseline. Seizure outcome was comparable between the left and right TLE patients. Before surgery, naming and word fluency were impaired in the left and right TLE patients, whereas sentence comprehension was normal. After left or right ATL, word fluency progressively improved, naming showed early worsening and late improvement after left ATL and progressive improvement after right ATL, and sentence comprehension did not change. At the 5-year follow-up, naming improvement was clinically significant in 31% and 71% of the left and right TLE patients, respectively. Pre-operative naming, ATL laterality, schooling, and post-operative seizure frequency and number of antiepileptic drugs predicted post-operative naming. Pre-operative word fluency and schooling predicted post-operative word fluency. Left or right TLE can impair word-finding but not sentence comprehension. After ATL, word-finding may improve for a long time, depending on TLE laterality, seizure control and mental reserve. These findings may clarify prognosis prior to treatment. © 2016 EAN.

Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

PubMed

Park, Chang-Hyun; Choi, Yun Seo; Jung, A-Reum; Chung, Hwa-Kyoung; Kim, Hyeon Jin; Yoo, Jeong Hyun; Lee, Hyang Woon

2017-01-01

Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

Memory Functions following Surgery for Temporal Lobe Epilepsy in Children

ERIC Educational Resources Information Center

Jambaque, Isabelle; Dellatolas, Georges; Fohlen, Martine; Bulteau, Christine; Watier, Laurence; Dorfmuller, Georg; Chiron, Catherine; Delalande, Olivier

2007-01-01

Surgical treatment appears to improve the cognitive prognosis in children undergoing surgery for temporal lobe epilepsy (TLE). The beneficial effects of surgery on memory functions, particularly on material-specific memory, are more difficult to assess because of potentially interacting factors such as age range, intellectual level,…

Disturbance of semantic processing in temporal lobe epilepsy demonstrated with scalp ERPs.

PubMed

Miyamoto, T; Katayama, J I; Kohsaka, M; Koyama, T

2000-12-01

We investigated event-related potentials (N400, LPC and CNV) elicited in temporal lobe epilepsy (TLE) patients and control subjects from scalp electrodes, using a word-pair category matching paradigm. Each prime consisted of a Japanese noun (constructed from 2-4 characters of the Hiragana) followed by a Chinese character (Kanji) as the target, the latter representing one of five semantic categories. There were two equally probable target conditions: match or mismatch. Each target was preceded by a prime, either belonging to, or not belonging to, the same semantic category. The subjects were required to respond with a specified button press to the given target, according to the condition. We found RTs to be longer under the mismatch condition in both subject groups. The N400 amplitude was reduced in TLE subjects under both conditions, although LPC and CNV amplitudes showed no significant differences. These results suggest that scalp N400 is capable of demonstrating disturbance of semantic processing in TLE non-invasively. Copyright 2000 BEA Trading Ltd.

Temporal Lobe Epilepsy: Quantitative MR Volumetry in Detection of Hippocampal Atrophy

PubMed Central

Farid, Nikdokht; Girard, Holly M.; Kemmotsu, Nobuko; Smith, Michael E.; Magda, Sebastian W.; Lim, Wei Y.; Lee, Roland R.

2012-01-01

Purpose: To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). Materials and Methods: This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration–cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. Results: Quantitative MR imaging–derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%–89.5%) and specificity (92.2%–94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. Conclusion: Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a useful and viable means for translating volumetric analysis into clinical practice. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112638/-/DC1 PMID:22723496

Hippocampus shape analysis for temporal lobe epilepsy detection in magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Kohan, Zohreh; Azmi, Reza

2016-03-01

There are evidences in the literature that Temporal Lobe Epilepsy (TLE) causes some lateralized atrophy and deformation on hippocampus and other substructures of the brain. Magnetic Resonance Imaging (MRI), due to high-contrast soft tissue imaging, is one of the most popular imaging modalities being used in TLE diagnosis and treatment procedures. Using an algorithm to help clinicians for better and more effective shape deformations analysis could improve the diagnosis and treatment of the disease. In this project our purpose is to design, implement and test a classification algorithm for MRIs based on hippocampal asymmetry detection using shape and size-based features. Our method consisted of two main parts; (1) shape feature extraction, and (2) image classification. We tested 11 different shape and size features and selected four of them that detect the asymmetry in hippocampus significantly in a randomly selected subset of the dataset. Then, we employed a support vector machine (SVM) classifier to classify the remaining images of the dataset to normal and epileptic images using our selected features. The dataset contains 25 patient images in which 12 cases were used as a training set and the rest 13 cases for testing the performance of classifier. We measured accuracy, specificity and sensitivity of, respectively, 76%, 100%, and 70% for our algorithm. The preliminary results show that using shape and size features for detecting hippocampal asymmetry could be helpful in TLE diagnosis in MRI.

Suicidality in temporal lobe epilepsy: measuring the weight of impulsivity and depression.

PubMed

de Oliveira, Guilherme Nogueira M; Kummer, Arthur; Salgado, João Vinícius; Filho, Gerardo Maria de Araújo; David, Anthony S; Teixeira, Antônio Lúcio

2011-12-01

The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE). Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale. A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P=0.012), current major depression (P=0.001), and motor impulsivity (P=0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR=12.82, 95% CI=2.58-63.76, P=0.002) and motor impulsivity (OR=1.21, 95% CI=1.06-1.38, P=0.005) to suicide risk. Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk. Copyright © 2011 Elsevier Inc. All rights reserved.

"Magnetic resonance imaging negative positron emission tomography positive" temporal lobe epilepsy: FDG-PET pattern differs from mesial temporal lobe epilepsy.

PubMed

Carne, R P; Cook, M J; MacGregor, L R; Kilpatrick, C J; Hicks, R J; O'Brien, T J

2007-01-01

Some patients with temporal lobe epilepsy (TLE) lack evidence of hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus. Thirty consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well-lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and 24 HS+ve patients. Both groups were compared using statistical parametric mapping (SPM), directly and with FDG-PET from 20 healthy controls. Both groups showed lateralized temporal hypometabolism compared to controls. In HS+ve, this was antero-infero-mesial (T = 17.13); in HS-ve the main clustering was inferolateral (T = 17.63). When directly compared, HS+ve had greater hypometabolism inmesial temporal/hippocampal regions (T = 4.86); HS-ve had greater inferolateral temporal hypometabolism (T = 4.18). These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in 'MRI-negative PET-positive TLE.'

Accelerated long-term forgetting and autobiographical memory disorders in temporal lobe epilepsy: One entity or two?

PubMed

Lemesle, B; Planton, M; Pagès, B; Pariente, J

Temporal lobe epilepsy (TLE) is a type of epilepsy that often has a negative impact on patients' memory. Despite the importance of patients' complaints in this regard, the difficulties described by these patients are often not easy to demonstrate through a standard neuropsychological assessment. Accelerated long-term forgetting and autobiographical memory disorders are the two main memory impairments reported in the literature in patients with TLE. However, the methods used by different authors to evaluate long-term memory and autobiographical memory are heterogeneous. This heterogeneity can lead to differences in the observed results as well as how they are interpreted. Yet, despite the methodological differences, objectification of such memory deficits appears to be both specific and robust within this patient population. Analysis of the literature shows that accelerated long-term forgetting and autobiographical memory disorders share the same clinical characteristics. This leads to the assumption that they are, in fact, only one entity and that their evaluation may be done through a single procedure. Our proposal is to place this evaluation within the context of memory consolidation disorders. With such a perspective, evaluation of accelerated forgetting in autobiographical memory should consist of identifying a disorder in the formation and/or recovery of new memory traces. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy.

PubMed

Szaflarski, Jerzy P; Allendorfer, Jane B

2012-05-01

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization. Copyright © 2012 Elsevier Inc. All rights reserved.

[A family with autosomal dominant temporal lobe epilepsy accompanied by motor and sensory neuropathy].

PubMed

Matsuoka, Takeshi; Furuya, Hirokazu; Ikezoe, Koji; Murai, Hiroyuki; Ohyagi, Yasumasa; Yoshiura, Takashi; Sasaki, Masayuki; Tobimatsu, Syozo; Kira, Jun-ichi

2004-01-01

We report a 20-year-old man with temporal lobe epilepsy (TLE) accompanied by hereditary motor and sensory neuropathy (HMSN). He had experienced complex partial seizures (CPS), which started with a nausea-like feeling, followed by loss of consciousness and automatism, since he was 6 years old. The frequency of attacks was at first decreased by phenytoin. However, attacks increased again when he was 18 years old. On admission, neurological examination showed mild weakness of the toes, pes cavus, hammer toe and mildly impaired vibratory sensation in his legs. Ten people in four generations of his family showed a history of epilepsy in the autosomal dominant inheritance form. His younger sister and mother had a history of epilepsy accompanied with pes cavus, hammer toe, weakness of toe and finger extension and mildly impaired vibratory sensation as well. Direct sequencing of the glioma-inactivated leucine-rich gene (LGI1), in which several mutations were reported in patients with familial lateral temporal lobe epilepsy, showed no specific mutation in this family. On consecutive video-EEG monitoring, paroxysmal rhythmic activity was confirmed in his left fronto-temporal region when he showed automatism, and then a generalized slow burst activity was detected when he lost consciousness. For his seizures, TLE with secondary generalization was diagnosed. In the nerve conduction study, delayed nerve conduction, distal motor latency and decreased amplitudes of the compound muscle action potentials (CMAP) of bilateral peroneal nerves were observed, indicating the existence of mild axonal degeneration. Based on these data, we consider that this family to be a new phenotype of autosomal dominant TLE accompanied by motor and sensory neuropathy.

Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery.

PubMed

Di Gennaro, Giancarlo; D'Aniello, Alfredo; De Risi, Marco; Grillea, Giovanni; Quarato, Pier Paolo; Mascia, Addolorata; Grammaldo, Liliana G; Casciato, Sara; Morace, Roberta; Esposito, Vincenzo; Picardi, Angelo

2015-11-01

To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up. We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.

PubMed

Haeren, R H L; Vink, H; Staals, J; van Zandvoort, M A M J; Dings, J; van Overbeeke, J J; Hoogland, G; Rijkers, K; Schijns, O E M G

2017-01-05

Adequate functioning of the blood-brain barrier (BBB) is important for brain homoeostasis and normal neuronal function. Disruption of the BBB has been described in several neurological diseases. Recent reports suggest that an increased permeability of the BBB also contributes to increased seizure susceptibility in patients with epilepsy. The endothelial glycocalyx is coating the luminal side of the endothelium and can be considered as the first barrier of the BBB. We hypothesise that an altered glycocalyx thickness plays a role in the aetiology of temporal lobe epilepsy (TLE), the most common type of epilepsy. Here, we propose a protocol that allows intraoperative assessment of the cerebrovascular glycocalyx thickness in patients with TLE and assess whether its thickness is decreased in patients with TLE when compared with controls. This protocol is designed as a prospective observational case-control study in patients who undergo resective brain surgery as treatment for TLE. Control subjects are patients without a history of epileptic seizures, who undergo a craniotomy or burr hole surgery for other indications. Intraoperative glycocalyx thickness measurements of sublingual, cortical and hippocampal microcirculation are performed by video microscopy using sidestream dark-field imaging. Demographic details, seizure characteristics, epilepsy risk factors, intraoperative haemodynamic parameters and histopathological evaluation are additionally recorded. This protocol has been ethically approved by the local medical ethical committee (ID: NL51594.068.14) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Informed consent is obtained before study enrolment and only coded data will be stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. NTR5568. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.

PubMed

Peixoto-Santos, Jose Eduardo; Velasco, Tonicarlo Rodrigues; Galvis-Alonso, Orfa Yineth; Araujo, David; Kandratavicius, Ludmyla; Assirati, Joao Alberto; Carlotti, Carlos Gilberto; Scandiuzzi, Renata Caldo; Santos, Antonio Carlos dos; Leite, Joao Pereira

2015-10-01

Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Epigenetic Histone Deacetylation Inhibition Prevents the Development and Persistence of Temporal Lobe Epilepsy.

PubMed

Reddy, Sandesh D; Clossen, Bryan L; Reddy, Doodipala Samba

2018-01-01

Epilepsy is a chronic brain disease characterized by repeated unprovoked seizures. Currently, no drug therapy exists for curing epilepsy or disease modification in people at risk. Despite several emerging mechanisms, there have been few studies of epigenetic signaling in epileptogenesis, the process whereby a normal brain becomes progressively epileptic because of precipitating factors. Here, we report a novel role of histone deacetylation as a critical epigenetic mechanism in epileptogenesis. Experiments were conducted using the histone deacetylase (HDAC) inhibitor sodium butyrate in the hippocampus kindling model of temporal lobe epilepsy (TLE), a classic model heavily used to approve drugs for treatment of epilepsy. Daily treatment with butyrate significantly inhibited HDAC activity and retarded the development of limbic epileptogenesis without affecting after-discharge signal. HDAC inhibition markedly impaired the persistence of seizure expression many weeks after epilepsy development. Moreover, subchronic HDAC inhibition for 2 weeks resulted in a striking retardation of epileptogenesis. HDAC inhibition, unexpectedly, also showed erasure of the epileptogenic state in epileptic animals. Finally, butyrate-treated animals exhibited a powerful reduction in mossy fiber sprouting, a morphologic index of epileptogenesis. Together these results underscore that HDAC inhibition prevents the development of TLE, indicating HDAC's critical signaling role in epileptogenesis. These findings, therefore, envisage a unique novel therapy for preventing or curing epilepsy by targeting the epigenetic HDAC pathway. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Kindling-Induced Changes in Plasticity of the Rat Amygdala and Hippocampus

ERIC Educational Resources Information Center

Schubert, Manja; Siegmund, Herbert; Pape, Hans-Christian; Albrecht, Doris

2005-01-01

Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar…

Microneurosurgical management of temporal lobe epilepsy by amygdalohippocampectomy (AH) plus standard anterior temporal lobectomy (ATL): a report of our initial five cases in Bangladesh

PubMed Central

Chowdhury, F H; Haque, M R; Islam, M S; Sarker, MH; Kawsar, KA; Sarker, AC

2010-01-01

Patient presenting as a case of Temporal Lobe Epilepsy (TLE) are usually resistant to antiepileptic drugs and surgery is the treatment of choice. This type of epilepsy may be due to Mesial Temporal Sclerosis (MTS), tumors [i.e. low grade glioma, Arterio-Venous Malformation (AVM) etc], trauma, infection (Tuberculosis) etc. Here we report five cases of surgically treated TLE that were due to a MTS, MTS with arachnoid cyst, low grade ganglioglioma, high grade ganglioglioma and a tuberculoma in the department of neurosurgery, Dhaka Medical College Hospital and Islami Bank Central Hospital, Dhaka, Bangladesh from August 2009 to February 2010. In all cases the only presenting symptoms was complex partial seizures (psychomotor epilepsy) for which all underwent scalp EEG (Electro Encephalogram) and MRI (Magnetic Resonance Imaging) of Brain. All patients were managed by amygdalohippocampectomy plus standard anterior lobectomy. One patient with high grade ganglioglioma recurred within two months of operation and expired within five months. The rest of the cases are seizure and disease free till the last follow up. PMID:22028754

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.

PubMed

Koyama, Ryuta; Tao, Kentaro; Sasaki, Takuya; Ichikawa, Junya; Miyamoto, Daisuke; Muramatsu, Rieko; Matsuki, Norio; Ikegaya, Yuji

2012-08-01

Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABA(A) receptors (GABA(A)-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABA(A)-Rs caused a reversal in the direction of granule cell migration. This abnormal migration was prevented by RNAi-mediated knockdown of the Na(+)K(+)2Cl(-) co-transporter (NKCC1), which regulates the excitatory action of GABA. NKCC1 inhibition with bumetanide after febrile seizures rescued the granule cell ectopia, susceptibility to limbic seizures and development of epilepsy. Thus, this work identifies a previously unknown pathogenic role of excitatory GABA(A)-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures.

A Novel RNA Editing Sensor Tool and a Specific Agonist Determine Neuronal Protein Expression of RNA-Edited Glycine Receptors and Identify a Genomic APOBEC1 Dimorphism as a New Genetic Risk Factor of Epilepsy

PubMed Central

Kankowski, Svenja; Förstera, Benjamin; Winkelmann, Aline; Knauff, Pina; Wanker, Erich E.; You, Xintian A.; Semtner, Marcus; Hetsch, Florian; Meier, Jochen C.

2018-01-01

C-to-U RNA editing of glycine receptors (GlyR) can play an important role in disease progression of temporal lobe epilepsy (TLE) as it may contribute in a neuron type-specific way to neuropsychiatric symptoms of the disease. It is therefore necessary to develop tools that allow identification of neuron types that express RNA-edited GlyR protein. In this study, we identify NH4 as agonist of C-to-U RNA edited GlyRs. Furthermore, we generated a new molecular C-to-U RNA editing sensor tool that detects Apobec-1- dependent RNA editing in HEPG2 cells and rat primary hippocampal neurons. Using this sensor combined with NH4 application, we were able to identify C-to-U RNA editing-competent neurons and expression of C-to-U RNA-edited GlyR protein in neurons. Bioinformatic analysis of 1,000 Genome Project Phase 3 allele frequencies coding for human Apobec-1 80M and 80I variants showed differences between populations, and the results revealed a preference of the 80I variant to generate RNA-edited GlyR protein. Finally, we established a new PCR-based restriction fragment length polymorphism (RFLP) approach to profile mRNA expression with regard to the genetic APOBEC1 dimorphism of patients with intractable temporal lobe epilepsy (iTLE) and found that the patients fall into two groups. Patients with expression of the Apobec-1 80I variant mostly suffered from simple or complex partial seizures, whereas patients with 80M expression exhibited secondarily generalized seizure activity. Thus, our method allows the characterization of Apobec-1 80M and 80l variants in the brain and provides a new way to epidemiologically and semiologically classify iTLE according to the two different APOBEC1 alleles. Together, these results demonstrate Apobec-1-dependent expression of RNA-edited GlyR protein in neurons and identify the APOBEC1 80I/M-coding alleles as new genetic risk factors for iTLE patients. PMID:29375302

Sleep affects cortical source modularity in temporal lobe epilepsy: A high-density EEG study.

PubMed

Del Felice, Alessandra; Storti, Silvia Francesca; Manganotti, Paolo

2015-09-01

Interictal epileptiform discharges (IEDs) constitute a perturbation of ongoing cerebral rhythms, usually more frequent during sleep. The aim of the study was to determine whether sleep influences the spread of IEDs over the scalp and whether their distribution depends on vigilance-related modifications in cortical interactions. Wake and sleep 256-channel electroencephalography (EEG) data were recorded in 12 subjects with right temporal lobe epilepsy (TLE) differentiated by whether they had mesial or neocortical TLE. Spikes were selected during wake and sleep. The averaged waking signal was subtracted from the sleep signal and projected on a bidimensional scalp map; sleep and wake spike distributions were compared by using a t-test. The superimposed signal of sleep and wake traces was obtained; the rising phase of the spike, the peak, and the deflections following the spike were identified, and their cortical generator was calculated using low-resolution brain electromagnetic tomography (LORETA) for each group. A mean of 21 IEDs in wake and 39 in sleep per subject were selected. As compared to wake, a larger IED scalp projection was detected during sleep in both mesial and neocortical TLE (p<0.05). A series of EEG deflections followed the spike, the cortical sources of which displayed alternating activations of different cortical areas in wake, substituted by isolated, stationary activations in sleep in mesial TLE and a silencing in neocortical TLE. During sleep, the IED scalp region increases, while cortical interaction decreases. The interaction of cortical modules in sleep and wake in TLE may influence the appearance of IEDs on scalp EEG; in addition, IEDs could be proxies for cerebral oscillation perturbation. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Increased expression of (immuno)proteasome subunits during epileptogenesis is attenuated by inhibition of the mammalian target of rapamycin pathway.

PubMed

Broekaart, Diede W M; van Scheppingen, Jackelien; Geijtenbeek, Karlijne W; Zuidberg, Mark R J; Anink, Jasper J; Baayen, Johannes C; Mühlebner, Angelika; Aronica, Eleonora; Gorter, Jan A; van Vliet, Erwin A

2017-08-01

Inhibition of the mammalian target of rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition of inflammatory processes, which may include the proteasome system. To study the role of mTOR inhibition in the regulation of the proteasome system, we investigated (immuno)proteasome expression during epileptogenesis, as well as the effects of the mTOR inhibitor rapamycin. The expression of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was investigated during epileptogenesis using immunohistochemistry in the electrical post-status epilepticus (SE) rat model for temporal lobe epilepsy (TLE). The effect of rapamycin was studied on (immuno)proteasome subunit expression in post-SE rats that were treated for 6 weeks. (Immuno)proteasome expression was validated in the brain tissue of patients who had SE or drug-resistant TLE and the effect of rapamycin was studied in primary human astrocyte cultures. In post-SE rats, increased (immuno)proteasome expression was detected throughout epileptogenesis in neurons and astrocytes within the hippocampus and piriform cortex and was most evident in rats that developed a progressive form of epilepsy. Rapamycin-treated post-SE rats had reduced (immuno)proteasome protein expression and a lower number of spontaneous seizures compared to vehicle-treated rats. (Immuno)proteasome expression was also increased in neurons and astrocytes within the human hippocampus after SE and in patients with drug-resistant TLE. In vitro studies using cultured human astrocytes showed that interleukin (IL)-1β-induced (immuno)proteasome gene expression could be attenuated by rapamycin. Because dysregulation of the (immuno)proteasome system is observed before the occurrence of spontaneous seizures in rats, is associated with progression of epilepsy, and can be modulated via the mTOR pathway, it may represent an interesting novel target for drug treatment in epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Expression of SHANK3 in the Temporal Neocortex of Patients with Intractable Temporal Epilepsy and Epilepsy Rat Models.

PubMed

Zhang, Yanke; Gao, Baobing; Xiong, Yan; Zheng, Fangshuo; Xu, Xin; Yang, Yong; Hu, Yida; Wang, Xuefeng

2017-07-01

SH3 and multiple ankyrin (ANK) repeat domain 3 (SHANK3) is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. SHANK3 plays an important role in the formation and maturation of excitatory synapses. In the brain, SHANK3 directly or indirectly interacts with various synaptic molecules including N-methyl-D-aspartate receptor, the metabotropic glutamate receptor (mGluR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Previous studies have shown that Autism spectrum disorder is a result of mutations of the main SHANK3 isoforms, which may be due to deficit in excitatory synaptic transmission and plasticity. Recently, accumulating evidence has demonstrated that overexpression of SHANK3 could induce seizures in vivo. However, little is known about the role of SHANK3 in refractory temporal lobe epilepsy (TLE). Therefore, we investigated the expression pattern of SHANK3 in patients with intractable temporal lobe epilepsy and in pilocarpine-induced models of epilepsy. Immunofluorescence, immunohistochemistry, and western blot analysis were used to locate and determine the expression of SHANK3 in the temporal neocortex of patients with epilepsy, and in the hippocampus and temporal lobe cortex of rats in a pilocarpine-induced epilepsy model. Double-labeled immunofluorescence showed that SHANK3 was mainly expressed in neurons. Western blot analysis confirmed that SHANK3 expression was increased in the neocortex of TLE patients and rats. These results indicate that SHANK3 participates in the pathology of epilepsy.

Epilepsy, Mental Health Disorder, or Both?

PubMed Central

Beletsky, Vadim; Mirsattari, Seyed M.

2012-01-01

Temporal lobe epilepsy (TLE), a subset of the seizure disorder family, represents a complex neuropsychiatric illness, where the neurological presentation may be complemented by varying severity of affective, behavioral, psychotic, or personality abnormalities, which, in turn, may not only lead to misdiagnosis, but also affect the management. This paper outlines a spectrum of mental health presentations, including psychosis, mood, anxiety, panic, and dissociative states, associated with epilepsy that make the correct diagnosis a challenge. PMID:22934158

Establishment of a rhesus monkey model of chronic temporal lobe epilepsy using repetitive unilateral intra-amygdala kainic acid injections.

PubMed

Chi, Yajie; Wu, Bolin; Guan, Jianwei; Xiao, Kuntai; Lu, Ziming; Li, Xiao; Xu, Yuting; Xue, Shan; Xu, Qiang; Rao, Junhua; Guo, Yanwu

2017-09-01

Temporal lobe epilepsy (TLE) is a common type of acquired epilepsy refractory to medical treatment. As such, establishing animal models of this disease is critical to developing new and effective treatment modalities. Because of their small head size, rodents are not suitable for comprehensive electroencephalography (EEG) evaluation via scalp or subdural electrodes. Therefore, a larger primate model that closely recapitulates signs of TLE is needed; here we describe a rhesus monkey model resembling chronic TLE. Eight monkeys were divided into two groups: kainic acid (KA) group (n=6) and saline control group (n=2). Intra-amygdala KA injections were performed biweekly via an Ommaya device until obvious epileptiform discharges were recorded. Video-EEG recording was conducted intermittently throughout the experiment using both scalp and subdural electrodes. Brains were then analyzed for Nissl and glial fibrillary acid protein (GFAP) immunostaining. After 2-4 injections of KA (approximately 1.2-2.4mg, 0.12-0.24mg/kg), interictal epileptiform discharges (IEDs) were recorded in all KA-treated animals. Spontaneous recurrent seizures (SRSs) accompanied by symptoms mimicking temporal lobe absence (undetectable without EEG recording), but few mild motor signs, were recorded in 66.7% (four of six) KA-treated animals. Both IEDs and seizures indicated a primary epileptic zone in the right temporal region and contralateral discharges were later detected. Segmental pyramidal cell loss and gliosis were detected in the brain of a KA-treated monkey. Through a modified protocol of unilateral repetitive intra-amygdala KA injections, a rhesus monkey model with similar behavioral and brain electrical features as TLE was developed. Copyright © 2017 Elsevier Inc. All rights reserved.

Temporal lobe epilepsy in patients with nonlesional MRI and normal memory: an SEEG study.

PubMed

Suresh, Suraj; Sweet, Jennifer; Fastenau, Philip S; Lüders, Hans; Landazuri, Patrick; Miller, Jonathan

2015-12-01

Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and memory deficits is often presumed to have an extramesial or even extratemporal source. In this paper the authors report the results of a comprehensive stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI images and memory scores. Eighteen patients with medically refractory epilepsy who also had unremarkable MR images and normal verbal and visual memory scores on neuropsychological testing were included in the study. All patients had seizure semiology and video electroencephalography (EEG) findings suggestive of TLE. A standardized SEEG investigation was performed for each patient with electrodes implanted into the mesial and lateral temporal lobe, temporal tip, posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate gyrus, and insula. This information was used to plan subsequent surgical management. Interictal SEEG abnormalities were observed in the mesial temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%). Seizure onset was exclusively from mesial structures in 13 (72%), exclusively from lateral temporal cortex and/or temporal tip structures in 2 (11%), and independently from mesial and neocortical foci in 3 (17%). No seizure activity was observed arising from any extratemporal location. All patients underwent surgical intervention targeting the temporal lobe and tailored to the SEEG findings, and all experienced significant improvement in seizure frequency with a postoperative follow-up observation period of at least 1 year. This study demonstrates 3 important findings: 1) normal memory does not preclude mesial temporal seizure onset; 2) onset of seizures exclusively from mesial temporal structures without early neocortical involvement is common, even in the absence of memory deficits; and 3) extratemporal seizure onset is rare when video EEG and semiology are consistent with focal TLE.

Sensitivity and specificity of memory and naming tests for identifying left temporal-lobe epilepsy.

PubMed

Umfleet, Laura Glass; Janecek, Julie K; Quasney, Erin; Sabsevitz, David S; Ryan, Joseph J; Binder, Jeffrey R; Swanson, Sara J

2015-01-01

The sensitivity and specificity of the Selective Reminding Test (SRT) Delayed Recall, Wechsler Memory Scale (WMS) Logical Memory, the Boston Naming Test (BNT), and two nonverbal memory measures for detecting lateralized dysfunction in association with side of seizure focus was examined in a sample of 143 patients with left or right temporal-lobe epilepsy (TLE). Scores on the SRT and BNT were statistically significantly lower in the left TLE group compared with the right TLE group, whereas no group differences emerged on the Logical Memory subtest. No significant group differences were found with nonverbal memory measures. When the SRT and BNT were both entered as predictors in a logistic regression, the BNT, although significant, added minimal value to the model beyond the variance accounted for by the SRT Delayed Recall. Both variables emerged as significant predictors of side of seizure focus when entered into separate regressions. Sensitivity and specificity of the SRT and BNT ranged from 56% to 65%. The WMS Logical Memory and nonverbal memory measures were not significant predictors of the side of seizure focus.

Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

PubMed

Di Gennaro, Giancarlo; Casciato, Sara; Quarato, Pier Paolo; Mascia, Addolorata; D'Aniello, Alfredo; Grammaldo, Liliana G; De Risi, Marco; Meldolesi, Giulio N; Romigi, Andrea; Esposito, Vincenzo; Picardi, Angelo

2015-01-01

To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Naming and recognizing famous faces in temporal lobe epilepsy.

PubMed

Glosser, G; Salvucci, A E; Chiaravalloti, N D

2003-07-08

To assess naming and recognition of faces of familiar famous people in patients with epilepsy before and after anterior temporal lobectomy (ATL). Color photographs of famous people were presented for naming and description to 63 patients with temporal lobe epilepsy (TLE) either before or after ATL and to 10 healthy age- and education-matched controls. Spontaneous naming of photographed famous people was impaired in all patient groups, but was most abnormal in patients who had undergone left ATL. When allowed to demonstrate knowledge of the famous faces through verbal descriptions, rather than naming, patients with left TLE, left ATL, and right TLE improved to normal levels, but patients with right ATL were still impaired, suggesting a new deficit in identifying famous faces. Naming of famous people was related to naming of other common objects, verbal memory, and perceptual discrimination of faces. Recognition of the identity of pictured famous people was more related to visuospatial perception and memory. Lesions in anterior regions of the right temporal lobe impair recognition of the identities of familiar faces, as well as the learning of new faces. Lesions in the left temporal lobe, especially in anterior regions, disrupt access to the names of known people, but do not affect recognition of the identities of famous faces. Results are consistent with the hypothesized role of lateralized anterior temporal lobe structures in facial recognition and naming of unique entities.

Alteration of functional connectivity within visuospatial working memory-related brain network in patients with right temporal lobe epilepsy: a resting-state fMRI study.

PubMed

Lv, Zong-xia; Huang, Dong-Hong; Ye, Wei; Chen, Zi-rong; Huang, Wen-li; Zheng, Jin-ou

2014-06-01

This study aimed to investigate the resting-state brain network related to visuospatial working memory (VSWM) in patients with right temporal lobe epilepsy (rTLE). The functional mechanism underlying the cognitive impairment in VSWM was also determined. Fifteen patients with rTLE and 16 healthy controls matched for age, gender, and handedness underwent a 6-min resting-state functional MRI session and a neuropsychological test using VSWM_Nback. The VSWM-related brain network at rest was extracted using multiple independent component analysis; the spatial distribution and the functional connectivity (FC) parameters of the cerebral network were compared between groups. Behavioral data were subsequently correlated with the mean Z-value in voxels showing significant FC difference during intergroup comparison. The distribution of the VSWM-related resting-state network (RSN) in the group with rTLE was virtually consistent with that in the healthy controls. The distribution involved the dorsolateral prefrontal lobe and parietal lobe in the right hemisphere and the partial inferior parietal lobe and posterior lobe of the cerebellum in the left hemisphere (p<0.05, AlphaSim corrected). Between-group differences suggest that the group with rTLE had a decreased FC within the right superior frontal lobe (BA8), right middle frontal lobe, and right ventromedial prefrontal lobe compared with the controls (p<0.05, AlphaSim corrected). The regions of increased FC in rTLE were localized within the right superior frontal lobe (BA11), right superior parietal lobe, and left posterior lobe of the cerebellum (p<0.05, AlphaSim corrected). Moreover, patients with rTLE performed worse than controls in the VSWM_Nback test, and there were negative correlations between ACCmeanRT (2-back) and the mean Z-value in the voxels showing decreased or increased FC in rTLE (p<0.05). The results suggest that the alteration of the VSWM-related RSN might underpin the VSWM impairment in patients with rTLE and possibly implies a functional compensation by enlarging the FC within the ipsilateral cerebral network. Copyright © 2014 Elsevier Inc. All rights reserved.

Early deficits in spatial memory and theta rhythm in experimental temporal lobe epilepsy.

PubMed

Chauvière, Laetitia; Rafrafi, Nadia; Thinus-Blanc, Catherine; Bartolomei, Fabrice; Esclapez, Monique; Bernard, Christophe

2009-04-29

Patients with temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, often display cognitive deficits. The time course and underlying mechanisms of cognitive decline remain unknown during epileptogenesis (the process leading to epilepsy). Using the rat pilocarpine model of TLE, we performed a longitudinal study to assess spatial and nonspatial cognitive performance during epileptogenesis. In parallel, we monitored interictal-like activity (ILA) in the hippocampal CA1 region, as well as theta oscillations, a brain rhythm central to numerous cognitive processes. Here, we report that spatial memory was altered soon after pilocarpine-induced status epilepticus, i.e., already during the seizure-free, latent period. Spatial deficits correlated with a decrease in the power of theta oscillations but not with the frequency of ILA. Spatial deficits persisted when animals had spontaneous seizures (chronic stage) without further modification. In contrast, nonspatial memory performances remained unaffected throughout. We conclude that the reorganization of hippocampal circuitry that immediately follows the initial insult can affect theta oscillation mechanisms, in turn, resulting in deficits in hippocampus-dependent memory tasks. These deficits may be dissociated from the process that leads to epilepsy itself but could instead constitute, as ILA, early markers in at-risk patients and/or provide beneficial therapeutic targets.

Automatic multimodal detection for long-term seizure documentation in epilepsy.

PubMed

Fürbass, F; Kampusch, S; Kaniusas, E; Koren, J; Pirker, S; Hopfengärtner, R; Stefan, H; Kluge, T; Baumgartner, C

2017-08-01

This study investigated sensitivity and false detection rate of a multimodal automatic seizure detection algorithm and the applicability to reduced electrode montages for long-term seizure documentation in epilepsy patients. An automatic seizure detection algorithm based on EEG, EMG, and ECG signals was developed. EEG/ECG recordings of 92 patients from two epilepsy monitoring units including 494 seizures were used to assess detection performance. EMG data were extracted by bandpass filtering of EEG signals. Sensitivity and false detection rate were evaluated for each signal modality and for reduced electrode montages. All focal seizures evolving to bilateral tonic-clonic (BTCS, n=50) and 89% of focal seizures (FS, n=139) were detected. Average sensitivity in temporal lobe epilepsy (TLE) patients was 94% and 74% in extratemporal lobe epilepsy (XTLE) patients. Overall detection sensitivity was 86%. Average false detection rate was 12.8 false detections in 24h (FD/24h) for TLE and 22 FD/24h in XTLE patients. Utilization of 8 frontal and temporal electrodes reduced average sensitivity from 86% to 81%. Our automatic multimodal seizure detection algorithm shows high sensitivity with full and reduced electrode montages. Evaluation of different signal modalities and electrode montages paces the way for semi-automatic seizure documentation systems. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Auditory temporal processing in patients with temporal lobe epilepsy.

PubMed

Lavasani, Azam Navaei; Mohammadkhani, Ghassem; Motamedi, Mahmoud; Karimi, Leyla Jalilvand; Jalaei, Shohreh; Shojaei, Fereshteh Sadat; Danesh, Ali; Azimi, Hadi

2016-07-01

Auditory temporal processing is the main feature of speech processing ability. Patients with temporal lobe epilepsy, despite their normal hearing sensitivity, may present speech recognition disorders. The present study was carried out to evaluate the auditory temporal processing in patients with unilateral TLE. The present study was carried out on 25 patients with epilepsy: 11 patients with right temporal lobe epilepsy and 14 with left temporal lobe epilepsy with a mean age of 31.1years and 18 control participants with a mean age of 29.4years. The two experimental and control groups were evaluated via gap-in-noise and duration pattern sequence tests. One-way ANOVA was run to analyze the data. The mean of the threshold of the GIN test in the control group was observed to be better than that in participants with LTLE and RTLE. Also, it was observed that the percentage of correct responses on the DPS test in the control group and in participants with RTLE was better than that in participants with LTLE. Patients with TLE have difficulties in temporal processing. Difficulties are more significant in patients with LTLE, likely because the left temporal lobe is specialized for the processing of temporal information. Copyright © 2016 Elsevier Inc. All rights reserved.

Methionine increases BDNF DNA methylation and improves memory in epilepsy.

PubMed

Parrish, R Ryley; Buckingham, Susan C; Mascia, Katherine L; Johnson, Jarvis J; Matyjasik, Michal M; Lockhart, Roxanne M; Lubin, Farah D

2015-04-01

Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus. Using the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model. We found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade. Our findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

Quantitative and qualitative analysis of semantic verbal fluency in patients with temporal lobe epilepsy.

PubMed

Jaimes-Bautista, A G; Rodríguez-Camacho, M; Martínez-Juárez, I E; Rodríguez-Agudelo, Y

2017-08-29

Patients with temporal lobe epilepsy (TLE) perform poorly on semantic verbal fluency (SVF) tasks. Completing these tasks successfully involves multiple cognitive processes simultaneously. Therefore, quantitative analysis of SVF (number of correct words in one minute), conducted in most studies, has been found to be insufficient to identify cognitive dysfunction underlying SVF difficulties in TLE. To determine whether a sample of patients with TLE had SVF difficulties compared with a control group (CG), and to identify the cognitive components associated with SVF difficulties using quantitative and qualitative analysis. SVF was evaluated in 25 patients with TLE and 24 healthy controls; the semantic verbal fluency test included 5 semantic categories: animals, fruits, occupations, countries, and verbs. All 5 categories were analysed quantitatively (number of correct words per minute and interval of execution: 0-15, 16-30, 31-45, and 46-60seconds); the categories animals and fruits were also analysed qualitatively (clusters, cluster size, switches, perseverations, and intrusions). Patients generated fewer words for all categories and intervals and fewer clusters and switches for animals and fruits than the CG (P<.01). Differences between groups were not significant in terms of cluster size and number of intrusions and perseverations (P>.05). Our results suggest an association between SVF difficulties in TLE and difficulty activating semantic networks, impaired strategic search, and poor cognitive flexibility. Attention, inhibition, and working memory are preserved in these patients. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Proton MRS may predict AED response in patients with TLE.

PubMed

Campos, Bruno A G; Yasuda, Clarissa L; Castellano, Gabriela; Bilevicius, Elizabeth; Li, Li M; Cendes, Fernando

2010-05-01

To compare relative N-acetylaspartate (NAA) measurements in temporal lobe epilepsy (TLE) patients with good response to the first trial of antiepileptic drugs (AEDs) (an important prognostic factor) to TLE patients who failed the first AED monotherapy and required further AED trials with monotherapy or polytherapy. We studied 25 consecutive TLE patients who responded to first AED (responders) and 21 who did not (failure-group), as well as 27 controls. Patients were seen regularly in our Epilepsy Service and underwent electroencephalography (EEG) investigation, high-resolution magnetic resonance imaging (MRI), and single-voxel proton MR spectroscopy. Voxels were tailored to the medial temporal region on each side and involved the anterior hippocampus. Analysis of variance (ANOVA) demonstrated significant variation of NAA/creatine (NAA/Cr) values in both hippocampi, ipsilateral and contralateral to the EEG focus (p < 0.001 and p = 0.021) across the groups. Pairwise post hoc comparisons showed reduced NAA/Cr in both hippocampi of failure-group compared to controls (p < 0.001) and compared to responders (p < 0.05), but not between the controls and responders. Individual analyses showed NAA/Cr ratios lower than 2 SDs (standard deviations) below the mean of controls in 9 of 21 patients (42.8%) in the failure-group (6 with unilateral and 3 with bilateral reduction) but in none of the responders. These results indicate that patients with TLE who respond well to the first AED have significantly less evidence of neuronal and axonal damage/dysfunction compared to those who are refractory to the first AED trial.

Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical outcomes

PubMed Central

Bonilha, Leonardo

2015-01-01

Medically intractable temporal lobe epilepsy (TLE) remains a serious health problem. Across treatment centers, up to 40% of patients with TLE will continue to experience persistent postoperative seizures at 2-year follow-up. It is unknown why such a large number of patients continue to experience seizures despite being suitable candidates for resective surgery. Preoperative quantitative MRI techniques may provide useful information on why some patients continue to experience disabling seizures, and may have the potential to develop prognostic markers of surgical outcome. In this article, we provide an overview of how quantitative MRI morphometric and diffusion tensor imaging (DTI) data have improved the understanding of brain structural alterations in patients with refractory TLE. We subsequently review the studies that have applied quantitative structural imaging techniques to identify the neuroanatomical factors that are most strongly related to a poor postoperative prognosis. In summary, quantitative imaging studies strongly suggest that TLE is a disorder affecting a network of neurobiological systems, characterized by multiple and inter-related limbic and extra-limbic network abnormalities. The relationship between brain alterations and postoperative outcome are less consistent, but there is emerging evidence suggesting that seizures are less likely to remit with surgery when presurgical abnormalities are observed in the connectivity supporting brain regions serving as network nodes located outside the resected temporal lobe. Future work, possibly harnessing the potential from multimodal imaging approaches, may further elucidate the etiology of persistent postoperative seizures in patients with refractory TLE. Furthermore, quantitative imaging techniques may be explored to provide individualized measures of postoperative seizure freedom outcome. PMID:25853080

Neural Stem Cell or Human Induced Pluripotent Stem Cell-derived GABA-ergic Progenitor Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy

PubMed Central

Upadhya, Dinesh; Hattiangady, Bharathi; Shetty, Geetha A.; Zanirati, Gabriele; Kodali, Maheedhar; Shetty, Ashok K.

2016-01-01

Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. PMID:27532817

Atypical febrile seizures, mesial temporal lobe epilepsy, and dual pathology.

PubMed

Sanon, Nathalie T; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE.

Comparative performance evaluation of automated segmentation methods of hippocampus from magnetic resonance images of temporal lobe epilepsy patients

PubMed Central

Hosseini, Mohammad-Parsa; Nazem-Zadeh, Mohammad-Reza; Pompili, Dario; Jafari-Khouzani, Kourosh; Elisevich, Kost; Soltanian-Zadeh, Hamid

2016-01-01

Purpose: Segmentation of the hippocampus from magnetic resonance (MR) images is a key task in the evaluation of mesial temporal lobe epilepsy (mTLE) patients. Several automated algorithms have been proposed although manual segmentation remains the benchmark. Choosing a reliable algorithm is problematic since structural definition pertaining to multiple edges, missing and fuzzy boundaries, and shape changes varies among mTLE subjects. Lack of statistical references and guidance for quantifying the reliability and reproducibility of automated techniques has further detracted from automated approaches. The purpose of this study was to develop a systematic and statistical approach using a large dataset for the evaluation of automated methods and establish a method that would achieve results better approximating those attained by manual tracing in the epileptogenic hippocampus. Methods: A template database of 195 (81 males, 114 females; age range 32–67 yr, mean 49.16 yr) MR images of mTLE patients was used in this study. Hippocampal segmentation was accomplished manually and by two well-known tools (FreeSurfer and hammer) and two previously published methods developed at their institution [Automatic brain structure segmentation (ABSS) and LocalInfo]. To establish which method was better performing for mTLE cases, several voxel-based, distance-based, and volume-based performance metrics were considered. Statistical validations of the results using automated techniques were compared with the results of benchmark manual segmentation. Extracted metrics were analyzed to find the method that provided a more similar result relative to the benchmark. Results: Among the four automated methods, ABSS generated the most accurate results. For this method, the Dice coefficient was 5.13%, 14.10%, and 16.67% higher, Hausdorff was 22.65%, 86.73%, and 69.58% lower, precision was 4.94%, −4.94%, and 12.35% higher, and the root mean square (RMS) was 19.05%, 61.90%, and 65.08% lower than LocalInfo, FreeSurfer, and hammer, respectively. The Bland–Altman similarity analysis revealed a low bias for the ABSS and LocalInfo techniques compared to the others. Conclusions: The ABSS method for automated hippocampal segmentation outperformed other methods, best approximating what could be achieved by manual tracing. This study also shows that four categories of input data can cause automated segmentation methods to fail. They include incomplete studies, artifact, low signal-to-noise ratio, and inhomogeneity. Different scanner platforms and pulse sequences were considered as means by which to improve reliability of the automated methods. Other modifications were specially devised to enhance a particular method assessed in this study. PMID:26745947

Accelerated long-term forgetting in children with temporal lobe epilepsy.

PubMed

Gascoigne, Michael B; Smith, Mary Lou; Barton, Belinda; Webster, Richard; Gill, Deepak; Lah, Suncica

2014-07-01

Adults with temporal lobe epilepsy (TLE) have been found to have accelerated long-term forgetting, but this phenomenon has not yet been investigated in children. Although deficits in recall of materials after short (20- to 30-minute) delays have been shown to slowly emerge from childhood to adolescence in patients with TLE, it is unknown whether such a trend will also be found in recall of materials after long delays. This study examined the presence of accelerated long-term forgetting in children with TLE and how it relates to chronological age. Twenty-three children with TLE and 58 healthy controls of similar age, sex distribution and socioeconomic status completed a battery of neuropsychological tests, including standardised tests of story recall and design location, as well as two experimental tests requiring the learning of words and design locations to a criterion, both of which assessed recall after short (30-min) and long (7-day) delays. Word recall at the 7-day delay (relative to the 30-min recall) was significantly poorer in the TLE group, compared to the control group. The TLE group also exhibited worse 30-min recall performance on a standardised test of story recall. Individual patient analyses revealed dissociation between performance on the experimental and standardised verbal memory tests; children who were impaired on the experimental test (7-day delay) were not impaired on the standardised test (30-min delay). Compared to controls, patients with a left-hemisphere seizure focus recalled fewer words at short and long delays while patients with an abnormal hippocampus recalled fewer words at the long delay. No between-group differences were found with respect to the design location task. Age negatively correlated with the recall of words after short- and long-term delays within the TLE group, where older age was associated with worse memory. This association was not present in the control group. To our knowledge, this is the first study to show evidence of accelerated long-term forgetting in children with TLE, which could not be explained by poor performance on standardised memory tests. Additionally, these results suggest that the developmental trajectory of long-term memory in children with TLE is similar to that of short-term memory: deficits emerge gradually, therefore older children are more likely to present with long-term memory deficits. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2016-08-01

instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke). This is followed by a...that define epileptic progression. 15. SUBJECT TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY CLASSIFICATION OF: U 17...grant, we will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of temporal lobe epilepsy (TLE), a

Comparative performance evaluation of automated segmentation methods of hippocampus from magnetic resonance images of temporal lobe epilepsy patients.

PubMed

Hosseini, Mohammad-Parsa; Nazem-Zadeh, Mohammad-Reza; Pompili, Dario; Jafari-Khouzani, Kourosh; Elisevich, Kost; Soltanian-Zadeh, Hamid

2016-01-01

Segmentation of the hippocampus from magnetic resonance (MR) images is a key task in the evaluation of mesial temporal lobe epilepsy (mTLE) patients. Several automated algorithms have been proposed although manual segmentation remains the benchmark. Choosing a reliable algorithm is problematic since structural definition pertaining to multiple edges, missing and fuzzy boundaries, and shape changes varies among mTLE subjects. Lack of statistical references and guidance for quantifying the reliability and reproducibility of automated techniques has further detracted from automated approaches. The purpose of this study was to develop a systematic and statistical approach using a large dataset for the evaluation of automated methods and establish a method that would achieve results better approximating those attained by manual tracing in the epileptogenic hippocampus. A template database of 195 (81 males, 114 females; age range 32-67 yr, mean 49.16 yr) MR images of mTLE patients was used in this study. Hippocampal segmentation was accomplished manually and by two well-known tools (FreeSurfer and hammer) and two previously published methods developed at their institution [Automatic brain structure segmentation (ABSS) and LocalInfo]. To establish which method was better performing for mTLE cases, several voxel-based, distance-based, and volume-based performance metrics were considered. Statistical validations of the results using automated techniques were compared with the results of benchmark manual segmentation. Extracted metrics were analyzed to find the method that provided a more similar result relative to the benchmark. Among the four automated methods, ABSS generated the most accurate results. For this method, the Dice coefficient was 5.13%, 14.10%, and 16.67% higher, Hausdorff was 22.65%, 86.73%, and 69.58% lower, precision was 4.94%, -4.94%, and 12.35% higher, and the root mean square (RMS) was 19.05%, 61.90%, and 65.08% lower than LocalInfo, FreeSurfer, and hammer, respectively. The Bland-Altman similarity analysis revealed a low bias for the ABSS and LocalInfo techniques compared to the others. The ABSS method for automated hippocampal segmentation outperformed other methods, best approximating what could be achieved by manual tracing. This study also shows that four categories of input data can cause automated segmentation methods to fail. They include incomplete studies, artifact, low signal-to-noise ratio, and inhomogeneity. Different scanner platforms and pulse sequences were considered as means by which to improve reliability of the automated methods. Other modifications were specially devised to enhance a particular method assessed in this study.

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Temporal lobe epilepsy: when are invasive recordings needed?

PubMed

Diehl, B; Lüders, H O

2000-01-01

Temporal lobe epilepsy (TLE) is the most common type of medically intractable partial epilepsy amenable to surgery. In the majority of cases, the underlying pathology in temporal lobe epilepsy is mesial temporal sclerosis (MTS). Whereas historically invasive recordings were required for most epilepsy surgeries, indications have dramatically changed since the introduction of high-resolution MRI, which uncovers structural lesions in a high percentage of cases. No invasive recordings are required to perform a temporal lobectomy in patients with intractable epilepsy who have structural imaging suggesting unilateral MTS and concordant interictal and ictal surface EEG recordings, functional imaging, and clinical findings. Invasive testing is needed if there is evidence of bitemporal MTS on structural imaging and/or electrophysiologically, and additional information from functional imaging, neuropsychology, and the intracarotid amobarbital (Wada) test also does not help to lateralize the epileptogenic zone. Depth electrodes can be particularly helpful in this setting. However, no surgery is indicated, even without invasive recordings, if bitemporal-independent seizures are recorded by surface EEG and all additional testing is inconclusive. Other etiologies of TLE such as a tumor, vascular malformation, encephalomalacia, or congenital developmental abnormality account for about 30% of all patients who undergo epilepsy surgery. Epilepsy surgery is indicated after limited electrophysiologic investigations if neuroimaging and electrophysiology converge. However, approaches for resection in lesional temporal lobe epilepsy vary among centers. Completeness of resection is crucial and invasive recordings may be needed to guide the resection by mapping eloquent cortex and/or to determine the extent of the non-MRI-visible epileptogenic area. Specific approaches for the different pathologies are discussed because there is evidence that the relationship between the lesions visible on MRI and the epileptogenic zone varies among lesions of different pathologies, and therefore variable surgical strategies must be applied.

Minimally invasive surgical approaches for temporal lobe epilepsy

PubMed Central

Chang, Edward F.; Englot, Dario J.; Vadera, Sumeet

2016-01-01

Surgery can be a highly effective treatment for medically refractory temporal lobe epilepsy (TLE). The emergence of minimally invasive resective and nonresective treatment options has led to interest in epilepsy surgery among patients and providers. Nevertheless, not all procedures are appropriate for all patients, and it is critical to consider seizure outcomes with each of these approaches, as seizure freedom is the greatest predictor of patient quality of life. Standard anterior temporal lobectomy (ATL) remains the gold standard in the treatment of TLE, with seizure freedom resulting in 60–80% of patients. It is currently the only resective epilepsy surgery supported by randomized controlled trials and offers the best protection against lateral temporal seizure onset. Selective amygdalohippocampectomy techniques preserve the lateral cortex and temporal stem to varying degrees and can result in favorable rates of seizure freedom but the risk of recurrent seizures appears slightly greater than with ATL, and it is not clear whether neuropsychological outcomes are improved with selective approaches. Stereotactic radiosurgery presents an opportunity to avoid surgery altogether, with seizure outcomes now under investigation. Stereotactic laser thermo-ablation allows destruction of the mesial temporal structures with low complication rates and minimal recovery time, and outcomes are also under study. Finally, while neuromodulatory devices such as responsive neurostimulation, vagus nerve stimulation, and deep brain stimulation have a role in the treatment of certain patients, these remain palliative procedures for those who are not candidates for resection or ablation, as complete seizure freedom rates are low. Further development and investigation of both established and novel strategies for the surgical treatment of TLE will be critical moving forward, given the significant burden of this disease. PMID:26017774

Altered Expression of CXCL13 and CXCR5 in Intractable Temporal Lobe Epilepsy Patients and Pilocarpine-Induced Epileptic Rats.

PubMed

Li, Ruohan; Ma, Limin; Huang, Hao; Ou, Shu; Yuan, Jinxian; Xu, Tao; Yu, Xinyuan; Liu, Xi; Yang, Juan; Chen, Yangmei; Peng, Xi

2017-02-01

The mechanisms that underlie the pathogenesis of epilepsy are still unclear. Recent studies have indicated that inflammatory processes occurring in the brain are involved in a common and crucial mechanism in epileptogenesis. C-X-C motif chemokine ligand 13 (CXCL13) and its only receptor, C-X-C motif chemokine receptor 5 (CXCR5), are highly expressed in the central nervous system (CNS) and participate in inflammatory responses. The present study aimed to assess the expression of CXCL13 and CXCR5 in the brain tissues of both patients with intractable epilepsy (IE) and a rat model (lithium-pilocarpine) of temporal lobe epilepsy (TLE) to identify possible roles of the CXCL13-CXCR5 signaling pathway in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemical, double-labeled immunofluorescence and Western blot analyses were performed in this study. CXCL13 and CXCR5 mRNA expression and protein levels were found to be significantly up-regulated in the TLE patients and TLE rats. Further, CXCL13 and CXCR5 protein levels were altered during the different epileptic phases after onset of status epilepticus (SE) in the pilocarpine model rats, including the acute phase (6, 24, and 72 h), latent phase (7 and 14 days) and chronic phase (30 and 60 days groups). Moreover, double-labeled immunofluorescence analysis revealed that CXCL13 was mainly expressed in the cytomembranes and cytoplasm of neurons and astrocytes, while CXCR5 was mainly expressed in the cytomembranes and cytoplasm of neurons. Thus, the CXCL13-CXCR5 signaling pathway may play a possible pathogenic role in IE. CXCL13 and CXCR5 may represent potential biomarkers of brain inflammation in epileptic patients.

Déjà-vu in temporal lobe epilepsy: metabolic pattern of cortical involvement in patients with normal brain MRI.

PubMed

Guedj, Eric; Aubert, Sandrine; McGonigal, Aileen; Mundler, Olivier; Bartolomei, Fabrice

2010-06-01

To contribute to the identification of brain regions involved in déjà-vu, we studied the metabolic pattern of cortical involvement in patients with seizures of temporal lobe origin presenting with or without déjà-vu. Using voxel-based analysis of 18FDG-PET brain scans, we compared glucose metabolic rate of 8 patients with déjà-vu, 8 patients without déjà-vu, and 20 age-matched healthy subjects. Patients were selected after comprehensive non-invasive presurgical evaluation, including normal brain MRI and surface electroclinical features compatible with unilateral temporal lobe epilepsy (TLE). Patients with and without déjà-vu did not differ in terms of age, gender, epilepsy lateralization, epilepsy onset, epilepsy duration, and other subjective ictal manifestations. TLE patients with déjà-vu exhibited ipsilateral hypometabolism of superior temporal gyrus and of parahippocampal region, in the vicinity of perirhinal/entorhinal cortex, in comparison either to healthy subjects or to TLE patients without déjà-vu (p<0.05 FDR-corrected). By contrast, no difference was found between patient subgroups for hypometabolism of hippocampus and amygdala. At an individual-level, in comparison to healthy subjects, hypometabolism of both parahippocampal region and superior temporal gyrus was present in 7/8 patients with déjà-vu. Hippocampal metabolism was spared in 3 of these 7 patients. These findings argue for metabolic dysfunction of a medial-lateral temporal network in patients with déjà-vu and normal brain MRI. Within the medial temporal lobe, specific involvement of the parahippocampal region, often in the absence of hippocampal impairment, suggests that the feeling of familiarity during seizures greatly depends on alteration of the recognition memory system. Copyright 2010 Elsevier Ltd. All rights reserved.

A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy

PubMed Central

Caciagli, Lorenzo; Bernasconi, Andrea; Wiebe, Samuel; Koepp, Matthias J.; Bernasconi, Neda

2017-01-01

Objective: It remains unclear whether drug-resistant temporal lobe epilepsy (TLE) is associated with cumulative brain damage, with no expert consensus and no quantitative syntheses of the available evidence. Methods: We conducted a systematic review and meta-analysis of MRI studies on progressive atrophy, searching PubMed and Ovid MEDLINE databases for cross-sectional and longitudinal quantitative MRI studies on drug-resistant TLE. Results: We screened 2,976 records and assessed eligibility of 248 full-text articles. Forty-two articles met the inclusion criteria for quantitative evaluation. We observed a predominance of cross-sectional studies, use of different clinical indices of progression, and high heterogeneity in age-control procedures. Meta-analysis of 18/1 cross-sectional/longitudinal studies on hippocampal atrophy (n = 979 patients) yielded a pooled effect size of r = −0.42 for ipsilateral atrophy related to epilepsy duration (95% confidence interval [CI] −0.51 to −0.32; p < 0.0001; I2 = 65.22%) and r = −0.35 related to seizure frequency (95% CI −0.47 to −0.22; p < 0.0001; I2 = 61.97%). Sensitivity analyses did not change the results. Narrative synthesis of 25/3 cross-sectional/longitudinal studies on whole brain atrophy (n = 1,504 patients) indicated that >80% of articles reported duration-related progression in extratemporal cortical and subcortical regions. Detailed analysis of study design features yielded low to moderate levels of evidence for progressive atrophy across studies, mainly due to dominance of cross-sectional over longitudinal investigations, use of diverse measures of seizure estimates, and absence of consistent age control procedures. Conclusions: While the neuroimaging literature is overall suggestive of progressive atrophy in drug-resistant TLE, published studies have employed rather weak designs to directly demonstrate it. Longitudinal multicohort studies are needed to unequivocally differentiate aging from disease progression. PMID:28687722

Atypical Febrile Seizures, Mesial Temporal Lobe Epilepsy, and Dual Pathology

PubMed Central

Sanon, Nathalie T.; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE. PMID:22957226

Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?

PubMed Central

Curia, G.; Lucchi, C.; Vinet, J.; Gualtieri, F.; Marinelli, C.; Torsello, A.; Costantino, L.; Biagini*,, G.

2014-01-01

Temporal lobe epilepsy (TLE) is frequently associated with hippocampal sclerosis, possibly caused by a primary brain injury that occurred a long time before the appearance of neurological symptoms. This type of epilepsy is characterized by refractoriness to drug treatment, so to require surgical resection of mesial temporal regions involved in seizure onset. Even this last therapeutic approach may fail in giving relief to patients. Although prevention of hippocampal damage and epileptogenesis after a primary event could be a key innovative approach to TLE, the lack of clear data on the pathophysiological mechanisms leading to TLE does not allow any rational therapy. Here we address the current knowledge on mechanisms supposed to be involved in epileptogenesis, as well as on the possible innovative treatments that may lead to a preventive approach. Besides loss of principal neurons and of specific interneurons, network rearrangement caused by axonal sprouting and neurogenesis are well known phenomena that are integrated by changes in receptor and channel functioning and modifications in other cellular components. In particular, a growing body of evidence from the study of animal models suggests that disruption of vascular and astrocytic components of the blood-brain barrier takes place in injured brain regions such as the hippocampus and piriform cortex. These events may be counteracted by drugs able to prevent damage to the vascular component, as in the case of the growth hormone secretagogue ghrelin and its analogues. A thoroughly investigation on these new pharmacological tools may lead to design effective preventive therapies. PMID:24251566

Psychoses in epilepsy: A comparison of postictal and interictal psychoses.

PubMed

Hilger, Eva; Zimprich, Friedrich; Pataraia, Ekaterina; Aull-Watschinger, Susanne; Jung, Rebekka; Baumgartner, Christoph; Bonelli, Silvia

2016-07-01

We retrospectively analyzed data of patients with epilepsy (n=1434) evaluated with prolonged EEG monitoring in order to estimate the prevalence of postictal psychosis (PP) and interictal psychosis (IP), to investigate a potential association of psychosis subtype with epilepsy type, and to assess differences between PP and IP. The overall prevalence of psychosis was 5.9% (N=85); prevalence of PP (N=53) and IP (N=32) was 3.7% and 2.2%, respectively. Of patients with psychosis, 97.6% had localization-related epilepsy (LRE). Prevalence of psychosis was highest (9.3%) in patients with temporal lobe epilepsy (TLE). When comparing PP with IP groups on demographic, clinical, and psychopathological variables, patients with IP were younger at occurrence of first psychosis (P=0.048), had a shorter interval between epilepsy onset and first psychosis (P=0.002), and more frequently exhibited schizophreniform traits (conceptual disorganization: P=0.008; negative symptoms: P=0.017) than those with PP. Postictal psychosis was significantly associated with a temporal seizure onset on ictal EEG (P=0.000) and a higher incidence of violent behavior during psychosis (P=0.047). To conclude, our results support the presumption of a preponderance of LRE in patients with psychosis and that of a specific association of TLE with psychosis, in particular with PP. Given the significant differences between groups, PP and IP may represent distinct clinical entities potentially with a different neurobiological background. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between neuronal network architecture and naming performance in temporal lobe epilepsy: A connectome based approach using machine learning.

PubMed

Munsell, B C; Wu, G; Fridriksson, J; Thayer, K; Mofrad, N; Desisto, N; Shen, D; Bonilha, L

2017-09-09

Impaired confrontation naming is a common symptom of temporal lobe epilepsy (TLE). The neurobiological mechanisms underlying this impairment are poorly understood but may indicate a structural disorganization of broadly distributed neuronal networks that support naming ability. Importantly, naming is frequently impaired in other neurological disorders and by contrasting the neuronal structures supporting naming in TLE with other diseases, it will become possible to elucidate the common systems supporting naming. We aimed to evaluate the neuronal networks that support naming in TLE by using a machine learning algorithm intended to predict naming performance in subjects with medication refractory TLE using only the structural brain connectome reconstructed from diffusion tensor imaging. A connectome-based prediction framework was developed using network properties from anatomically defined brain regions across the entire brain, which were used in a multi-task machine learning algorithm followed by support vector regression. Nodal eigenvector centrality, a measure of regional network integration, predicted approximately 60% of the variance in naming. The nodes with the highest regression weight were bilaterally distributed among perilimbic sub-networks involving mainly the medial and lateral temporal lobe regions. In the context of emerging evidence regarding the role of large structural networks that support language processing, our results suggest intact naming relies on the integration of sub-networks, as opposed to being dependent on isolated brain areas. In the case of TLE, these sub-networks may be disproportionately indicative naming processes that are dependent semantic integration from memory and lexical retrieval, as opposed to multi-modal perception or motor speech production. Copyright © 2017. Published by Elsevier Inc.

Temporal lobe epilepsy: quantitative MR volumetry in detection of hippocampal atrophy.

PubMed

Farid, Nikdokht; Girard, Holly M; Kemmotsu, Nobuko; Smith, Michael E; Magda, Sebastian W; Lim, Wei Y; Lee, Roland R; McDonald, Carrie R

2012-08-01

To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration-cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. Quantitative MR imaging-derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%-89.5%) and specificity (92.2%-94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a useful and viable means for translating volumetric analysis into clinical practice.

Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy

PubMed Central

Richardson, Mark P.; Schoene‐Bake, Jan‐Christoph; O'Muircheartaigh, Jonathan; Elkommos, Samia; Kreilkamp, Barbara; Goh, Yee Yen; Marson, Anthony G.; Elger, Christian; Weber, Bernd

2015-01-01

Objective There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI). Methods We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy. Results Quantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI‐derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection. Interpretation Patients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group‐based findings to individualize prediction of patient outcomes. Ann Neurol 2015;77:760–774 PMID:25627477

Rabies Tracing of Birthdated Dentate Granule Cells in Rat Temporal Lobe Epilepsy

PubMed Central

Du, Xi; Zhang, Helen; Parent, Jack M.

2017-01-01

Objective To understand how monosynaptic inputs onto adult-born dentate granule cells (DGCs) are altered in experimental mesial temporal lobe epilepsy (mTLE) and whether their integration differs from early-born DGCs that are mature at the time of epileptogenesis. Methods A dual-virus tracing strategy combining retroviral birthdating with rabies virus-mediated putative retrograde trans-synaptic tracing was used to identify and compare presynaptic inputs onto adult- and early-born DGCs in the rat pilocarpine model of mTLE. Results Our results demonstrate that hilar ectopic DGCs preferentially synapse onto adult-born DGCs after pilocarpine-induced status epilepticus (SE) while normotopic DGCs synapse onto both adult- and early-born DGCs. We also find that parvalbumin+ and somatostatin+ interneuron inputs are greatly diminished onto early-born DGCs after SE. However, somatostatin+ interneuron inputs onto adult-born DGCs are maintained, likely due to preferential sprouting. Intriguingly, CA3 pyramidal cell backprojections that specifically target adult-born DGCs arise in the epileptic brain, while axons of interneurons and pyramidal cells in CA1 appear to sprout across the hippocampal fissure to preferentially synapse onto early-born DGCs. Interpretation These data support the presence of substantial hippocampal circuit remodeling after an epileptogenic insult that generates prominent excitatory monosynaptic inputs, both local recurrent and widespread feedback loops, involving DGCs. Both adult- and early-born DGCs are targets of new inputs from other DGCs as well as from CA3 and CA1 pyramidal cells after pilocarpine-treatment, changes that likely contribute to epileptogenesis in experimental mTLE. PMID:28470680

Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy.

PubMed

Liu, Bei; Niu, Le; Shen, Ming-Zhi; Gao, Lei; Wang, Chao; Li, Jie; Song, Li-Jia; Tao, Ye; Meng, Qiang; Yang, Qian-Li; Gao, Guo-Dong; Zhang, Hua

2014-10-01

Efflux of monocaroxylates like lactate, pyruvate, and ketone bodies from astrocytes through monocarboxylate transporter 4 (MCT4) supplies the local neuron population with metabolic intermediates to meet energy requirements under conditions of increased demand. Disruption of this astroglial-neuron metabolic coupling pathway may contribute to epileptogenesis. We measured MCT4 expression in temporal lobe epileptic foci excised from patients with intractable epilepsy and in rats injected with pilocarpine, an animal model of temporal lobe epilepsy (TLE). Cortical MCT4 expression levels were significantly lower in TLE patients compared with controls, due at least partially to MCT4 promoter methylation. Expression of MCT4 also decreased progressively in pilocarpine-treated rats from 12 h to 14 days post-administration. Underexpression of MCT4 in cultured astrocytes induced by a short hairpin RNA promoted apoptosis. Knockdown of astrocyte MCT4 also suppressed excitatory amino acid transporter 1 (EAAT1) expression. Reduced MCT4 and EAAT1 expression by astrocytes may lead to neuronal hyperexcitability and epileptogenesis in the temporal lobe by reducing the supply of metabolic intermediates and by allowing accumulation of extracellular glutamate.

Short-term and long-term memory in early temporal lobe dysfunction.

PubMed

Hershey, T; Craft, S; Glauser, T A; Hale, S

1998-01-01

Following medial temporal damage, mature humans are impaired in retaining new information over long delays but not short delays. The question of whether a similar dissociation occurs in children was addressed by testing children (ages 7-16) with unilateral temporal lobe epilepsy (TLE) and controls on short- and long-term memory tasks, including a spatial delayed response task (SDR). Early-onset TLE did not affect performance on short delays on SDR, but it did impair performance at the longest delay (60 s), similar to adults with unilateral medial temporal damage. In addition, early-onset TLE affected performance on pattern recall, spatial span, and verbal span with rehearsal interference. No differences were found on story recall or on a response inhibition task.

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI.

PubMed

Limotai, Chusak; McLachlan, Richard S; Hayman-Abello, Susan; Hayman-Abello, Brent; Brown, Suzan; Bihari, Frank; Mirsattari, Seyed M

2018-06-19

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.

PubMed

Wirsich, Jonathan; Perry, Alistair; Ridley, Ben; Proix, Timothée; Golos, Mathieu; Bénar, Christian; Ranjeva, Jean-Philippe; Bartolomei, Fabrice; Breakspear, Michael; Jirsa, Viktor; Guye, Maxime

2016-01-01

The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

The impact of intelligence on memory and executive functions of children with temporal lobe epilepsy: Methodological concerns with clinical relevance.

PubMed

Rzezak, Patricia; Guimarães, Catarina A; Guerreiro, Marilisa M; Valente, Kette D

2017-05-01

Patients with TLE are prone to have lower IQ scores than healthy controls. Nevertheless, the impact of IQ differences is not usually considered in studies that compared the cognitive functioning of children with and without epilepsy. This study aimed to determine the effect of using IQ as a covariate on memory and attentional/executive functions of children with TLE. Thirty-eight children and adolescents with TLE and 28 healthy controls paired as to age, gender, and sociodemographic factors were evaluated with a comprehensive neuropsychological battery for memory and executive functions. The authors conducted three analyses to verify the impact of IQ scores on the other cognitive domains. First, we compared performance on cognitive tests without controlling for IQ differences between groups. Second, we performed the same analyses, but we included IQ as a confounding factor. Finally, we evaluated the predictive value of IQ on cognitive functioning. Although patients had IQ score in the normal range, they showed lower IQ scores than controls (p = 0.001). When we did not consider IQ in the analyses, patients had worse performance in verbal and visual memory (short and long-term), semantic memory, sustained, divided and selective attention, mental flexibility and mental tracking for semantic information. By using IQ as a covariate, patients showed worse performance only in verbal memory (long-term), semantic memory, sustained and divided attention and in mental flexibility. IQ was a predictor factor of verbal and visual memory (immediate and delayed), working memory, mental flexibility and mental tracking for semantic information. Intelligence level had a significant impact on memory and executive functioning of children and adolescents with TLE without intellectual disability. This finding opens the discussion of whether IQ scores should be considered when interpreting the results of differences in cognitive performance of patients with epilepsy compared to healthy volunteers. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model.

PubMed

Lösing, Pascal; Niturad, Cristina Elena; Harrer, Merle; Reckendorf, Christopher Meyer Zu; Schatz, Theresa; Sinske, Daniela; Lerche, Holger; Maljevic, Snezana; Knöll, Bernd

2017-07-17

A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance. Adult conditional SRF deficient mice (Srf CaMKCreERT2 ) were more refractory to initial status epilepticus (SE) acquisition. Further, SRF deficient mice developed more spontaneous recurrent seizures (SRS). Genome-wide transcriptomic analysis uncovered a requirement of SRF for SE and SRS induced IEG induction (e.g. Fos, Egr1, Arc, Npas4, Btg2, Atf3). SRF was required for epilepsy associated neurodegeneration, mossy fiber sprouting and inflammation. We uncovered MAP kinase signaling as SRF target during epilepsy. Upon SRF ablation, seizure evoked induction of dual specific phosphatases (Dusp5 and Dusp6) was reduced. Lower expression of these negative ERK kinase regulators correlated with altered P-ERK levels in epileptic Srf mutant animals.Overall, this study uncovered an SRF contribution to several processes of epileptogenesis in the pilocarpine model.

Proper name retrieval in temporal lobe epilepsy: naming of famous faces and landmarks.

PubMed

Benke, Thomas; Kuen, Eva; Schwarz, Michael; Walser, Gerald

2013-05-01

The objective of this study was to further explore proper name (PN) retrieval and conceptual knowledge in patients with left and right temporal lobe epilepsy (69 patients with LTLE and 62 patients with RTLE) using a refined assessment procedure. Based on the performance of a large group of age- and education-matched normals, a new test of famous faces and famous landmarks was designed. Recognition, naming, and semantic knowledge were assessed consecutively, allowing for a better characterization of deficient levels in the naming system. Impairment in PN retrieval was common in the cohort with TLE. Furthermore, side of seizure onset impaired stages of name retrieval differently: LTLE impaired the lexico-phonological processing, whereas RTLE mainly impaired the perceptual-semantic stage of object recognition. In addition to deficient PN retrieval, patients with TLE had reduced conceptual knowledge regarding famous persons and landmarks. Copyright © 2013 Elsevier Inc. All rights reserved.

Neuronal zinc-α2-glycoprotein is decreased in temporal lobe epilepsy in patients and rats.

PubMed

Liu, Ying; Wang, Teng; Liu, Xi; Wei, Xin; Xu, Tao; Yin, Maojia; Ding, Xueying; Mo, Lijuan; Chen, Lifen

2017-08-15

Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used. The existence and level of ZAG in the brain were identified using immunohistochemistry, double-labeled immunofluorescence and western blot, and the expression level of AZGP1 mRNA was determined with quantitative real-time polymerase chain reaction (qrt-PCR). To explore the potential biological role of ZAG in the brain, co-immunoprecipitation (Co-IP) of phosphorylated ERK (p-ERK), TGF-β1 and ZAG was also performed. ZAG was found in the cytoplasm of neurons in brain tissue from both patients and rats. The levels of AZGP1 mRNA and ZAG were lower in refractory TLE patients and PTZ-kindled rats than in controls. In addition, the ZAG level decreased as PTZ kindling continued. Co-IP identified direct binding between p-ERK, TGF-β1 and ZAG. ZAG was found to be synthesized in neurons, and both the AZGP1 mRNA and ZAG protein levels were decreased in epilepsy patients and rat models. The reduction in ZAG may participate in the pathogenesis and pathophysiology of epilepsy by interacting with p-ERK and TGF-β1, promoting inflammation, regulating the metabolism of ketone bodies, or affecting other epilepsy-related molecules. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Does education play a role in language reorganization after surgery in drug refractory temporal lobe epilepsy: An fMRI based study?

PubMed

Chaudhary, Kapil; Ramanujam, Bhargavi; Kumaran, S Senthil; Chandra, P Sarat; Wadhawan, Ashima Nehra; Garg, Ajay; Tripathi, Manjari

2017-10-01

Patients with drug refractory epilepsy (DRE) and a high level of education may differ in their language recovery after surgery. Our aim was to determine whether there were differences in the extent of improvement and pattern of reorganization of language functions on functional magnetic resonance imaging (fMRI) after surgery to treat refractory temporal lobe epilepsy (TLE) between patients with more than 12 years of formal education versus those with a shorter period of regular schooling. After approval by an institutional ethics committee, 60 right-handed, adult patients of left TLE and 20 right-handed, healthy controls were recruited to the study. Multiple aspects of language (Repetition, Naming, Word fluency, Visual word and Comprehension reading) were tested using the Indian Aphasia Battery (IAB) in the Hindi language; fMRI was performed using a standardized Hindi language paradigm (lexical, semantic, syntactic and comprehension components) in both cases and controls, before and after an anterior temporal lobectomy (in cases) with a 1.5T MR Scanner. An array of performance tests of intelligence and the verbal adult intelligence scale (VAIS) were used to measure the Intelligence Quotient (IQ) in Left TLE (LTLE) patients before and after surgery. Language laterality was estimated using the laterality index (LI-toolbox-spm8). Cohen's d test was performed to determine the effect sizes of the differences in the IAB scores, and Pearson's correlation was applied between regional (IFG and STG) activation in controls and TLE patients with more than 12 years of schooling [higher educational status (HES subgroup)] and those with less than 12 years of schooling [lower educational status (LES subgroup)]. At the baseline, clinical testing with IAB showed better scores in controls than in cases. Better scores were observed in subjects with higher levels of education than in those with lower levels of education. An improvement was observed in IQ scores in both the HES and LES groups after ATLR; significant worsening in the abstract ability subtest was noted in the LES group, whereas in the HES group there was an improvement. Blood-oxygen-level dependent (BOLD) activation during language tasks was observed in both cerebral hemispheres in the TLE cases, while it was observed in the traditional left hemispheric language areas in controls. Postoperatively, greater BOLD activation was observed in the left inferior frontal gyri (IFG, r=0.65 * ; p<0.05), middle frontal gyrus (MFG, r=0.77 ** ; p<0.01) superior temporal gyri (STG, r=0.88 * p<0.02) and angular gyrus (AG, r=0.73 * ; p<0.04) in HES compared to LES subjects. Similarly, LI showed left lateralization of the frontal (LIw=0.77 & 0.71) and temporal (LIw=0.74 & 0.5) regions in controls and the TLE group (post-surgery) compared to the pre-surgery group during language tasks. Greater improvement in language skills and BOLD activation in the left hemisphere in TLE-patients (after epilepsy surgery) with a high level of education was similar to that of healthy controls, implying that education has an effect on the functional reorganization/recovery of language areas. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteomic analysis and comparison of the biopsy and autopsy specimen of human brain temporal lobe.

PubMed

He, Sizhi; Wang, Qingsong; He, Jintang; Pu, Hai; Yang, Wei; Ji, Jianguo

2006-09-01

The proteomic study on human temporal lobe can help us to understand the physiological function of CNS in normal as well as in pathological state. Proteomic tools are potent for the assessment of protein stability post mortem. In this pilot study, the human temporal lobe biopsy specimen with chronic pharmacoresistant temporal lobe epilepsy (TLE) and autopsy specimen in control were separated by 2-DE. Using MALDI-TOF-MS and MS/MS, 375 protein spots were identified which were the products of 267 genes. Six down-regulated and 23 up-regulated protein spots in the autopsy specimen were ascertained after the gel image analysis with the ImageMaster software. A number of proteins that include neurotransmitter metabolic and glycolytic enzymes, cytoprotective proteins and cytoskeleton were found decreased while the precursor of apolipoprotein A-I increased in the TLE brain. We tried several methods to prepare the protein samples and found that DNase and RNase treatment, ultracentrifugation and Amersham clean-up kit purification can improve gel separation quality. This work optimized the sample preparation method and constructed a primary protein database of human temporal lobe and found some proteins with remarkable level change probably involved in the post-mortem process and chronic pharmacoresistant TLE pathogenesis.

In vivo MRS and MRSI: Performance analysis, measurement considerations and evaluation of metabolite concentration images

NASA Astrophysics Data System (ADS)

Vikhoff-Baaz, Barbro

2000-10-01

The doctoral thesis concerns development, evaluation and performance of quality assessment methods for volume- selection methods in 31P and 1H MR spectroscopy (MRS). It also contains different aspects of the measurement procedure for 1H MR spectroscopic imaging (MRSI) with application on the human brain, image reconstruction of the MRSI images and evaluation methods for lateralization of temporal lobe epilepsy (TLE). Two complementary two-compartment phantoms and evaluation methods for quality assessment of 31P MRS in small-bore MR systems were presented. The first phantom consisted of an inner cube inside a sphere phantom where measurements with and without volume selection where compared for various VOI sizes. The multi-centre showed that the evaluated parameters provide useful information of the performance of volume-selective MRS at the MR system. The second phantom consisted of two compartments divided by a very thin wall and was found useful for measurements of the appearance and position of the VOI profile in specific gradient directions. The second part concerned 1H MRS and MRSI of whole-body MR systems. Different factors that may degrade or complicate the measurement procedure like for MRSI were evaluated, e.g. the volume selection performance, contamination, susceptibility and motion. Two interpolation methods for reconstruction of MRSI images were compared. Measurements and computer simulations showed that Fourier interpolation correctly visualizes the information inherent in the data set, while the results were dependent on the position of the object relative the original matrix using Cubic spline interpolation. Application of spatial filtering may improve the image representation of the data. Finally, 1H MRSI was performed on healthy volunteers and patients with temporal lobe epilepsy (TLE). Metabolite concentration images were used for lateralization of TLE, where the signal intensity in the two hemispheres were compared. Visual analysis of the metabolite concentration images can, with high accuracy, be used for lateralization in routine examinations. Analysis from measurements with region-of-interests (ROI) in different locations gives quantitative information about the degree of signal loss and the spatial distribution.

Daytime outpatient versus inpatient video-EEG monitoring for presurgical evaluation in temporal lobe epilepsy.

PubMed

Guerreiro, Carlos A M; Montenegro, Maria Augusta; Kobayashi, Eliane; Noronha, Ana Lúcia A; Guerreiro, Marilisa M; Cendes, Fernando

2002-06-01

Video-EEG monitoring documentation of seizure localization is one of the most important aspects of a presurgical investigation in refractory temporal lobe epilepsy (TLE) patients. The objective of this study was to evaluate the efficacy of inpatient versus daytime outpatient telemetry. The authors evaluated prospectively 73 patients with medically intractable TLE. Ninety-one telemetry sessions were performed: 35 as inpatients and 56 as outpatients. Outpatient monitoring was performed in the EEG laboratory. They used 18-channel digital EEG. Medications were not changed in the outpatient group. For analysis of the data, time was counted in periods (12 hours = 1 period). Statistical analyses were performed using Student's t-test and the chi2 test. There were no differences between the two groups (outpatient versus inpatient) with respect to age and mean seizure frequency before monitoring, mean time to record the first seizure (1.1 versus 1.4 periods), mean number of seizures per period (0.6 for both groups), lateralization by interictal spiking (46% versus 57%), and lateralization by ictal EEG (59% versus 77%). Daytime outpatient video-EEG monitoring for presurgical evaluation is efficient and comparable with inpatient monitoring. Therefore, the improved cost benefit of outpatient monitoring may increase the access to surgery for individuals with intractable TLE.

Interval analysis of interictal EEG: pathology of the alpha rhythm in focal epilepsy

NASA Astrophysics Data System (ADS)

Pyrzowski, Jan; Siemiński, Mariusz; Sarnowska, Anna; Jedrzejczak, Joanna; Nyka, Walenty M.

2015-11-01

The contemporary use of interictal scalp electroencephalography (EEG) in the context of focal epilepsy workup relies on the visual identification of interictal epileptiform discharges. The high-specificity performance of this marker comes, however, at a cost of only moderate sensitivity. Zero-crossing interval analysis is an alternative to Fourier analysis for the assessment of the rhythmic component of EEG signals. We applied this method to standard EEG recordings of 78 patients divided into 4 subgroups: temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), psychogenic nonepileptic seizures (PNES) and nonepileptic patients with headache. Interval-analysis based markers were capable of effectively discriminating patients with epilepsy from those in control subgroups (AUC~0.8) with diagnostic sensitivity potentially exceeding that of visual analysis. The identified putative epilepsy-specific markers were sensitive to the properties of the alpha rhythm and displayed weak or non-significant dependences on the number of antiepileptic drugs (AEDs) taken by the patients. Significant AED-related effects were concentrated in the theta interval range and an associated marker allowed for identification of patients on AED polytherapy (AUC~0.9). Interval analysis may thus, in perspective, increase the diagnostic yield of interictal scalp EEG. Our findings point to the possible existence of alpha rhythm abnormalities in patients with epilepsy.

Histopathologic subtype of hippocampal sclerosis and episodic memory performance before and after temporal lobectomy for epilepsy.

PubMed

Saghafi, Shahram; Ferguson, Lisa; Hogue, Olivia; Gales, Jordan M; Prayson, Richard; Busch, Robyn M

2018-04-01

The International League Against Epilepsy (ILAE) proposed a classification system for hippocampal sclerosis (HS) based on location and extent of hippocampal neuron loss. The literature debates the usefulness of this classification system when studying memory in people with temporal lobe epilepsy (TLE) and determining memory outcome after temporal lobe resection (TLR). This study further explores the relationship between HS ILAE subtypes and episodic memory performance in patients with TLE and examines memory outcomes after TLR. This retrospective study identified 213 patients with TLE who underwent TLR and had histopathological evidence of HS (HS ILAE type 1a = 92; type 1b = 103; type 2 = 18). Patients completed the Wechsler Memory Scale-3rd Edition prior to surgery, and 78% of patients had postoperative scores available. Linear regressions examined differences in preoperative memory scores as a function of pathology classification, controlling for potential confounders. Fisher's exact tests were used to compare pathology subtypes on the magnitude of preoperative memory impairment and the proportion of patients who experienced clinically meaningful postoperative memory decline. Individuals with HS ILAE type 2 demonstrated better preoperative verbal memory performance than patients with HS ILAE type 1; however, individual data revealed verbal and visual episodic memory impairments in many patients with HS ILAE type 2. The base rate of postoperative memory decline was similar among all 3 pathology groups. This is the largest reported overall sample and the largest subset of patients with HS ILAE type 2. Group data suggest that patients with HS ILAE type 2 perform better on preoperative memory measures, but individually there were no differences in the magnitude of memory impairment. Following surgery, there were no statistically significant differences between groups in the proportion of patients who declined. Future research should focus on quantitative measurements of hippocampal neuronal loss, and multicenter collaboration is encouraged. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Resting-state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

PubMed Central

Doucet, Gaëlle E.; Pustina, Dorian; Skidmore, Christopher; Sharan, Ashwini; Sperling, Michael R.; Tracy, Joseph I.

2015-01-01

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post-surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting-state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting-state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left-hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. PMID:25187327

Lateralization of temporal lobe epilepsy by multimodal multinomial hippocampal response-driven models.

PubMed

Nazem-Zadeh, Mohammad-Reza; Elisevich, Kost V; Schwalb, Jason M; Bagher-Ebadian, Hassan; Mahmoudi, Fariborz; Soltanian-Zadeh, Hamid

2014-12-15

Multiple modalities are used in determining laterality in mesial temporal lobe epilepsy (mTLE). It is unclear how much different imaging modalities should be weighted in decision-making. The purpose of this study is to develop response-driven multimodal multinomial models for lateralization of epileptogenicity in mTLE patients based upon imaging features in order to maximize the accuracy of noninvasive studies. The volumes, means and standard deviations of FLAIR intensity and means of normalized ictal-interictal SPECT intensity of the left and right hippocampi were extracted from preoperative images of a retrospective cohort of 45 mTLE patients with Engel class I surgical outcomes, as well as images of a cohort of 20 control, nonepileptic subjects. Using multinomial logistic function regression, the parameters of various univariate and multivariate models were estimated. Based on the Bayesian model averaging (BMA) theorem, response models were developed as compositions of independent univariate models. A BMA model composed of posterior probabilities of univariate response models of hippocampal volumes, means and standard deviations of FLAIR intensity, and means of SPECT intensity with the estimated weighting coefficients of 0.28, 0.32, 0.09, and 0.31, respectively, as well as a multivariate response model incorporating all mentioned attributes, demonstrated complete reliability by achieving a probability of detection of one with no false alarms to establish proper laterality in all mTLE patients. The proposed multinomial multivariate response-driven model provides a reliable lateralization of mesial temporal epileptogenicity including those patients who require phase II assessment. Copyright © 2014 Elsevier B.V. All rights reserved.

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: an electrocorticography study.

PubMed

Morales Chacón, L; Estupiñán, B; Lorigados Pedre, L; Trápaga Quincoses, O; García Maeso, I; Sanchez, A; Bender del Busto, J; Garcia, M E; Baez Martin, M; Zaldivar, M; Gómez, A; Orozco, S; Rocha Arrieta, L

2009-10-01

Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy.

PubMed

Zhou, Zhike; Liu, Tingting; Sun, Xiaoyu; Mu, Xiaopeng; Zhu, Gang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

2017-03-30

It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE. Copyright © 2017 Elsevier B.V. All rights reserved.

Cyclic alternating pattern and interictal epileptiform discharges during morning sleep after sleep deprivation in temporal lobe epilepsy.

PubMed

Giorgi, Filippo Sean; Maestri, Michelangelo; Guida, Melania; Carnicelli, Luca; Caciagli, Lorenzo; Ferri, Raffaele; Bonuccelli, Ubaldo; Bonanni, Enrica

2017-08-01

Sleep deprivation (SD) increases the occurrence of interictal epileptiform discharges (IED) compared to basal EEG in temporal lobe epilepsy (TLE). In adults, EEG after SD is usually performed in the morning after SD. We aimed to evaluate whether morning sleep after SD bears additional IED-inducing effects compared with nocturnal physiological sleep, and whether changes in sleep stability (described by the cyclic alternating pattern-CAP) play a significant role. Adult patients with TLE underwent in-lab night polysomnography (n-PSG) and, within 7days from n-PSG, they underwent also a morning EEG after night SD (SD-EEG). We included only TLE patients in which both recordings showed IED. SD-EEG consisted of waking up patients at 2:00 AM and performing video EEG at 8:00 AM. For both recordings, we obtained the following markers for the first sleep cycle: IED/h (Spike Index, SI), sleep macrostructure, microstructure (NREM CAP rate; A1, A2 and A3 Indices), and SI association with CAP variables. The macrostructure of the first sleep cycle was similar in n-PSG and morning SD-EEG, whereas CAP rate and SI were significantly higher in SD-EEG. SI increase was selectively associated with CAP phases. SD increases the instability of morning recovery sleep compared with n-PSG, and particularly enhances CAP A1 phases, which are associated with the majority of IED. Thus, higher instability of morning recovery sleep may account at least in part for the increased IED yield in SD-EEG in TLE patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in the sensitivity of GABAA current rundown to drug treatments in a model of temporal lobe epilepsy

PubMed Central

Cifelli, Pierangelo; Palma, Eleonora; Roseti, Cristina; Verlengia, Gianluca; Simonato, Michele

2013-01-01

The pharmacological treatment of mesial temporal lobe epilepsy (mTLE), the most common epileptic syndrome in adults, is still unsatisfactory, as one-third of the patients are or become refractory to antiepileptic agents. Refractoriness may depend upon drug-induced alterations, but the disease per se may also undergo a progressive evolution that affects the sensitivity to drugs. mTLE has been shown to be associated with a dysfunction of the inhibitory signaling mediated by GABAA receptors. In particular, the repetitive activation of GABAA receptors produces a use-dependent decrease (rundown) of the evoked currents (IGABA), which is markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients. This phenomenon has been also observed in the pilocarpine model, where the increased IGABA rundown is observed in the hippocampus at the time of the first spontaneous seizure, then extends to the cortex and remains constant in the chronic phase of the disease. Here, we examined the sensitivity of IGABA to pharmacological modulation. We focused on the antiepileptic agent levetiracetam (LEV) and on the neurotrophin brain-derived neurotrophic factor (BDNF), which were previously reported to attenuate mTLE-induced increased rundown in the chronic human tissue. In the pilocarpine model, BDNF displayed a paramount effect, decreasing rundown in the hippocampus at the time of the first seizure, as well as in the hippocampus and cortex in the chronic period. In contrast, LEV did not affect rundown in the hippocampus, but attenuated it in the cortex. Interestingly, this effect of LEV was also observed on the still unaltered rundown observed in the cortex at the time of the first spontaneous seizure. These data suggest that the sensitivity of GABAA receptors to pharmacological interventions undergoes changes during the natural history of mTLE, implicating that the site of seizure initiation and the timing of treatment may highly affect the therapeutic outcome. PMID:23874269

Famous face identification in temporal lobe epilepsy: Support for a multimodal integration model of semantic memory

PubMed Central

Drane, Daniel L.; Ojemann, Jeffrey G.; Phatak, Vaishali; Loring, David W.; Gross, Robert E.; Hebb, Adam O.; Silbergeld, Daniel L.; Miller, John W.; Voets, Natalie L.; Saindane, Amit M.; Barsalou, Lawrence; Meador, Kimford J.; Ojemann, George A.; Tranel, Daniel

2012-01-01

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre-and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts. PMID:23040175

Famous face identification in temporal lobe epilepsy: support for a multimodal integration model of semantic memory.

PubMed

Drane, Daniel L; Ojemann, Jeffrey G; Phatak, Vaishali; Loring, David W; Gross, Robert E; Hebb, Adam O; Silbergeld, Daniel L; Miller, John W; Voets, Natalie L; Saindane, Amit M; Barsalou, Lawrence; Meador, Kimford J; Ojemann, George A; Tranel, Daniel

2013-06-01

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre- and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Microsurgical techniques in temporal lobe epilepsy.

PubMed

Alonso Vanegas, Mario A; Lew, Sean M; Morino, Michiharu; Sarmento, Stenio A

2017-04-01

Temporal lobe resection is the most prevalent epilepsy surgery procedure. However, there is no consensus on the best surgical approach to treat temporal lobe epilepsy. Complication rates are low and efficacy is very high regarding seizures after such procedures. However, there is still ample controversy regarding the best surgical approach to warrant maximum seizure control with minimal functional deficits. We describe the most frequently used microsurgical techniques for removal of both the lateral and mesial temporal lobe structures in the treatment of medically intractable temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (corticoamygdalohippocampectomy and selective amygdalohippocampectomy). The choice of surgical technique appears to remain a surgeon's preference for the near future. Meticulous surgical technique and thorough three-dimensional microsurgical knowledge are essentials for obtaining the best results. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Silencing miR-181a produces neuroprotection against hippocampus neuron cell apoptosis post-status epilepticus in a rat model and in children with temporal lobe epilepsy.

PubMed

Ren, L; Zhu, R; Li, X

2016-02-22

Epilepsy is one of the most frequent neurological disorders. Recently, the regulation of microRNAs was found to be associated with epilepsy, but the molecular mechanism by which microRNA influences epilepsy process remains to be unveiled and the development of microRNA-based therapy requires more intensive research. In this study, five microRNAs with potential relevance to epilepsy were initially chosen: miR-132, miR-146a, miR-181a, miR-34a, and miR-124. Twenty-five children who were patients with epilepsy were selected as subjects to obtain tissue samples for the study. The miRNA-181a, which represented the most increased fold-changes in clinical samples, were then selected for further function study in mouse model. The temporal lobe epilepsy (TLE) model, along with lithium-pilocarpine-induced status epilepticus (SE), was established in Sprague-Dawley rats. The antagomir of miR-181a was used to determine the role of miR-181a in cell apoptosis. Analyses were conducted to determine the expression levels of miR-181a, neuronal apoptosis in post-SE, and activated caspase-3. We found evidence of significant time dependent up-regulation of miR-181a amongst post-SE rats and TLE on 24 h (4.47 ± 0.35), 7 days (4.85 ± 0.53), and 2 weeks (5.66 ± 0.64). Experiments with the miR-181a antagomir showed that this particular miRNA led to the inhibition of the protein expression of caspase-3, and was up-regulated in the course of seizure-induced neuronal apoptosis. This study provided evidence that targeting miR-181a leads to a neuroprotective response and is linked to an increase in the activation of the caspase-3 protein. These findings suggest that miR-181a may serve as a promising therapeutic target for epilepsy.

A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.

PubMed

Amini, Elham; Rezaei, Mohsen; Mohamed Ibrahim, Norlinah; Golpich, Mojtaba; Ghasemi, Rasoul; Mohamed, Zahurin; Raymond, Azman Ali; Dargahi, Leila; Ahmadiani, Abolhassan

2015-08-01

Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.

The predictive value of FDG-PET with 3D-SSP for surgical outcomes in patients with temporal lobe epilepsy.

PubMed

Higo, Takuma; Sugano, Hidenori; Nakajima, Madoka; Karagiozov, Kostadin; Iimura, Yasushi; Suzuki, Masaru; Sato, Kiyoshi; Arai, Hajime

2016-10-01

We retrospectively evaluated the diagnostic value of (18)F-2-fluorodeoxy-d-glucose positron emission tomography (FDG-PET) with statistical analysis for the foci detection and predictive utility for postsurgical seizure outcome of patients with mesial temporal lobe epilepsy (mTLE). We evaluated 40 patients who were diagnosed mTLE and underwent selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) in our institute. Preoperative interictal FDG-PET with statistical analysis using three-dimensional stereotactic surface projection (3D-SSP) was detected with several clinical data including seizure semiology, MRI, scalp electroencephalography, surgical procedure with SAH or ATL and postsurgical outcome. The region of interest (ROI) was defined on 'Hippocampus & Amygdala', 'Parahippocampal gyrus & Uncus', 'T1 & T2', and 'T3 & Fusiform gyrus'. We obtained the ratio of hypometabolism difference (RHD) by 3D-SSP, and evaluated the relation among hypometabolic extent, surgical outcome and surgical procedure. The RHD in each ROIs ipsilateral to operative side was significantly higher than that of contralateral side in good outcome group. Hypometabolism of 'Hippocampus & Amygdala' was most reliable prognostic factor. Patients of discordant with presurgical examinations hardly showed obvious lateralized hypometabolism. Nevertheless, when they have significantly high RHD in mesial temporal lobe, good surgical outcome was expected. There was not significant difference of RHD distribution between SAH and ATL in good outcome group. Significant hypometabolism in mesial temporal lobe on FDG-PET with 3D-SSP is useful to predict good surgical outcome for patients with mTLE, particularly in discordant patients with hypometabolism in mesial temporal structure. However, FDG-PET is not indicative of surgical procedure. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Evaluation of focus laterality in temporal lobe epilepsy: a quantitative study comparing double inversion-recovery MR imaging at 3T with FDG-PET.

PubMed

Morimoto, Emiko; Okada, Tomohisa; Kanagaki, Mitsunori; Yamamoto, Akira; Fushimi, Yasutaka; Matsumoto, Riki; Takaya, Shigetoshi; Ikeda, Akio; Kunieda, Takeharu; Kikuchi, Takayuki; Paul, Dominik; Miyamoto, Susumu; Takahashi, Ryosuke; Togashi, Kaori

2013-12-01

To quantitatively compare the diagnostic capability of double inversion-recovery (DIR) with F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE). This study was approved by the institutional review board, and written informed consent was obtained. Fifteen patients with TLE and 38 healthy volunteers were enrolled. All magnetic resonance (MR) images were acquired using a 3T-MRI system. Voxel-based analysis (VBA) was conducted for FDG-PET images and white matter segments of DIR images (DIR-WM) focused on the whole temporal lobe (TL) and the anterior part of the temporal lobe (ATL). Distribution of hypometabolic areas on FDG-PET and increased signal intensity areas on DIR-WM were evaluated, and their laterality was compared with clinically determined seizure focus laterality. Correct diagnostic rates of laterality were evaluated, and agreement between DIR-WM and FDG-PET was assessed using κ statistics. Increased signal intensity areas on DIR-WM were located at the vicinity of the hypometabolic areas on FDG-PET, especially in the ATL. Correct diagnostic rates of seizure focus laterality for DIR-WM (0.80 and 0.67 for the TL and the ATL, respectively) were slightly higher than those for FDG-PET (0.67 and 0.60 for the TL and the ATL, respectively). Agreement of laterality between DIR-WM and FDG-PET was substantial for the TL and almost perfect for the ATL (κ = 0.67 and 0.86, respectively). High agreement in localization between DIR-WM and FDG-PET and nearly equivalent detectability of them show us an additional role of MRI in TLE. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Localized shape abnormalities in the thalamus and pallidum are associated with secondarily generalized seizures in mesial temporal lobe epilepsy.

PubMed

Yang, Linglin; Li, Hong; Zhu, Lujia; Yu, Xinfeng; Jin, Bo; Chen, Cong; Wang, Shan; Ding, Meiping; Zhang, Minming; Chen, Zhong; Wang, Shuang

2017-05-01

Mesial temporal lobe epilepsy (mTLE) is a common type of drug-resistant epilepsy and secondarily generalized tonic-clonic seizures (sGTCS) have devastating consequences for patients' safety and quality of life. To probe the mechanism underlying the genesis of sGTCS, we investigated the structural differences between patients with and without sGTCS in a cohort of mTLE with radiologically defined unilateral hippocampal sclerosis. We performed voxel-based morphometric analysis of cortex and vertex-wise shape analysis of subcortical structures (the basal ganglia and thalamus) on MRI of 39 patients (21 with and 18 without sGTCS). Comparisons were initially made between sGTCS and non-sGTCS groups, and subsequently made between uncontrolled-sGTCS and controlled-sGTCS subgroups. Regional atrophy of the ipsilateral ventral pallidum (cluster size=450 voxels, corrected p=0.047, Max voxel coordinate=107, 120, 65), medial thalamus (cluster size=1128 voxels, corrected p=0.049, Max voxel coordinate=107, 93, 67), middle frontal gyrus (cluster size=60 voxels, corrected p<0.05, Max voxel coordinate=-30, 49.5, 6), and contralateral posterior cingulate cortex (cluster size=130 voxels, corrected p<0.05, Max voxel coordinate=16.5, -57, 27) was found in the sGTCS group relative to the non-sGTCS group. Furthermore, the uncontrolled-sGTCS subgroup showed more pronounced atrophy of the ipsilateral medial thalamus (cluster size=1240 voxels, corrected p=0.014, Max voxel coordinate=107, 93, 67) than the controlled-sGTCS subgroup. These findings indicate a central role of thalamus and pallidum in the pathophysiology of sGTCS in mTLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Seizure outcome in pediatric medically refractory temporal lobe epilepsy surgery: selective amygdalohippocampectomy versus anterior temporal lobectomy.

PubMed

Elliott, Cameron A; Broad, Andrew; Narvacan, Karl; Steve, Trevor A; Snyder, Thomas; Urlacher, Jordan; Wheatley, B Matt; Sinclair, D Barry

2018-06-22

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the initial operation was significantly more likely following ATL (47/61, 77%) than SelAH (8/18, 44%; p = 0.017, Fisher's exact test). There was no statistically significant difference in the proportion of patients with postoperative neuropsychological deficits following SelAH (8/18, 44%) or ATL (21/61, 34%). However, reoperation was significantly more likely following SelAH (8/18, 44%) than after ATL (7/61, 11%; p = 0.004) and was more likely to result in Engel I outcome for ATL after failed SelAH (7/8, 88%) than for posterior extension after failed ATL (1/7, 14%; p = 0.01). Reoperation was well tolerated without significant neuropsychological deterioration. Ultimately, including 15 reoperations, 58 of 79 (73%) patients were free from disabling seizures at the most recent follow-up. CONCLUSIONS SelAH among pediatric patients with medically refractory unilateral TLE yields significantly worse rates of seizure control compared with ATL. Reoperation is significantly more likely following SelAH, is not associated with incremental neuropsychological deterioration, and frequently results in freedom from disabling seizures. These results are significant in that they argue against using SelAH for pediatric TLE surgery.

Phosphatase inhibitors remove the run-down of γ-aminobutyric acid type A receptors in the human epileptic brain

PubMed Central

Palma, E.; Ragozzino, D. A.; Di Angelantonio, S.; Spinelli, G.; Trettel, F.; Martinez-Torres, A.; Torchia, G.; Arcella, A.; Di Gennaro, G.; Quarato, P. P.; Esposito, V.; Cantore, G.; Miledi, R.; Eusebi, F.

2004-01-01

The properties of γ-aminobutyric acid (GABA) type A receptors (GABAA receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABAA receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat α1β2γ2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABAA receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABAA receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocytes recapitulates essentially what occurs in neurons, rather than in glial cells. Quantitative RT-PCR analyses from the same TLE neocortex specimens revealed that GABAA-receptor β1, β2, β3, and γ2 subunit mRNAs were significantly overexpressed (8- to 33-fold) compared with control autopsy tissues. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE brain leads to the expression of run-down-enhanced GABAA receptors. Blockage of phosphatases stabilizes the TLE GABAA receptors and strengthens GABAergic inhibition. It may be that this process can be targeted to develop new treatments for intractable epilepsy. PMID:15218107

Resting-state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals.

PubMed

Doucet, Gaëlle E; Pustina, Dorian; Skidmore, Christopher; Sharan, Ashwini; Sperling, Michael R; Tracy, Joseph I

2015-01-01

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post-surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting-state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting-state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left-hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. © 2014 Wiley Periodicals, Inc.

Memory outcome 2 years after anterior temporal lobectomy in patients with drug-resistant epilepsy.

PubMed

Grammaldo, Liliana G; Di Gennaro, Giancarlo; Giampà, Teresa; De Risi, Marco; Meldolesi, Giulio N; Mascia, Addolorata; Sparano, Antonio; Esposito, Vincenzo; Quarato, Pier Paolo; Picardi, Angelo

2009-03-01

Memory decline is often observed after anterior temporal lobectomy (ATL), particularly in patients with dominant hemisphere resections. However, the follow-up length has been 1 year or less in most studies. Our aims were to examine postoperative memory changes over a longer period and to identify baseline demographic and clinical predictors of memory outcome. We administered material-specific memory tests at baseline, and 1 and 2 years after surgery to 82 consecutive right-handed patients (52% males) who underwent ATL for drug-resistant temporal lobe epilepsy (TLE) (35 left, 47 right) after a non-invasive presurgical protocol. Repeated measures multivariate analysis of variance (RM-MANOVA) was used to examine the relationship between changes in memory tests scores over time and side of TLE and pathology. Also, standardized residual change scores were calculated for each memory test and entered in multiple linear regression models aimed at identifying baseline predictors of better memory outcome. RM-MANOVA revealed a significant change in memory test scores over time, with an interaction between time and side of surgery, as 2 years after surgery patients with RTLE were improved while patients with LTLE were not worse as compared with baseline. Pathology was not associated with changes in memory scores. In multiple regression analysis, significant associations were found between right TLE and greater improvement in verbal memory, younger age and greater improvement in visuospatial memory, and male gender and greater improvement in both verbal and visuospatial memory. Our results suggest that the long-term memory outcome of TLE patients undergoing ATL without invasive presurgical assessment may be good in most cases not only for right-sided but also for left-sided resections.

Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase.

PubMed

Buono, R J; Ferraro, T N; O'Connor, M J; Sperling, M R; Abbey, M; Finanger, E; Lohoff, F; Mulholland, N; Berrettini, W H

2000-02-07

Genetic linkage studies in rodents and humans have identified specific chromosomal regions harboring seizure susceptibility genes. We have identified a novel polymorphism in the human alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase (NaK-pump), a candidate gene for human temporal lobe epilepsy (TLE) based on its chromosomal location and function in ion homeostasis. The polymorphism consists of a four base pair insertion 12 base pairs upstream of the start of exon 2. We performed an association study between this polymorphism and TLE. Our study did not find a significant difference in the frequency of this polymorphism between TLE patients and controls, indicating that this variation is not a major susceptibility factor. However, since the number of patients studied so far is small and the functional consequence of the polymorphism is unknown, the variation may yet be found to play a minor role in increased risk for seizure susceptibility. In contrast to the findings in TLE patients and controls, we did find a significant difference in the frequency of the variation between African Americans and persons of European descent. This finding demonstrates the potential effect of population stratification on studies of this type and supports the growing use of parental and familial samples for controls in association studies. Further study of this polymorphism is warranted as it may be involved in other disease processes for which there are known ethnic-specific susceptibilities. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:79-83, 2000. Copyright 2000 Wiley-Liss, Inc.

Looking for complexity in quantitative semiology of frontal and temporal lobe seizures using neuroethology and graph theory.

PubMed

Bertti, Poliana; Tejada, Julian; Martins, Ana Paula Pinheiro; Dal-Cól, Maria Luiza Cleto; Terra, Vera Cristina; de Oliveira, José Antônio Cortes; Velasco, Tonicarlo Rodrigues; Sakamoto, Américo Ceiki; Garcia-Cairasco, Norberto

2014-09-01

Epileptic syndromes and seizures are the expression of complex brain systems. Because no analysis of complexity has been applied to epileptic seizure semiology, our goal was to apply neuroethology and graph analysis to the study of the complexity of behavioral manifestations of epileptic seizures in human frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). We analyzed the video recordings of 120 seizures of 18 patients with FLE and 28 seizures of 28 patients with TLE. All patients were seizure-free >1 year after surgery (Engel Class I). All patients' behavioral sequences were analyzed by means of a glossary containing all behaviors and analyzed for neuroethology (Ethomatic software). The same series were used for graph analysis (CYTOSCAPE). Behaviors, displayed as nodes, were connected by edges to other nodes according to their temporal sequence of appearance. Using neuroethology analysis, we confirmed data in the literature such as in FLE: brief/frequent seizures, complex motor behaviors, head and eye version, unilateral/bilateral tonic posturing, speech arrest, vocalization, and rapid postictal recovery and in the case of TLE: presence of epigastric aura, lateralized dystonias, impairment of consciousness/speech during ictal and postictal periods, and development of secondary generalization. Using graph analysis metrics of FLE and TLE confirmed data from flowcharts. However, because of the algorithms we used, they highlighted more powerfully the connectivity and complex associations among behaviors in a quite selective manner, depending on the origin of the seizures. The algorithms we used are commonly employed to track brain connectivity from EEG and MRI sources, which makes our study very promising for future studies of complexity in this field. Copyright © 2014 Elsevier Inc. All rights reserved.

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool.

PubMed

Del Felice, Alessandra; Magalini, Alessandra; Masiero, Stefano

2015-01-01

Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 μV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE. Copyright © 2015 Elsevier Inc. All rights reserved.

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients.

PubMed

Stewart, Christopher C; Griffith, H Randall; Okonkwo, Ozioma C; Martin, Roy C; Knowlton, Robert K; Richardson, Elizabeth J; Hermann, Bruce P; Seidenberg, Michael

2009-02-01

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.

ALA-induced PpIX fluorescence in epileptogenic tissue

NASA Astrophysics Data System (ADS)

Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

Evidence for degraded low frequency verbal concepts in left resected temporal lobe epilepsy patients.

PubMed

Visser, M; Forn, C; Lambon Ralph, M A; Hoffman, P; Gómez Ibáñez, A; Sunajuán, Ana; Rosell Negre, P; Villanueva, V; Ávila, C

2018-06-01

According to a large neuropsychological and neuroimaging literature, the bilateral anterior temporal lobe (ATL) is a core region for semantic processing. It seems therefore surprising that semantic memory appears to be preserved in temporal lobe epilepsy (TLE) patients with unilateral ATL resection. However, recent work suggests that the bilateral semantic system is relatively robust against unilateral damage and semantic impairments under these circumstances only become apparent with low frequency specific concepts. In addition, neuroimaging studies have shown that the function of the left and right ATLs differ and therefore left or right ATL resection should lead to a different pattern of impairment. The current study investigated hemispheric differences in the bilateral semantic system by comparing left and right resected TLE patients during verbal semantic processing of low frequency concepts. Picture naming and semantic comprehension tasks with varying word frequencies were included to investigate the pattern of impairment. Left but not right TLE patients showed impaired semantic processing, which was particularly apparent on low frequency items. This indicates that, for verbal information, the bilateral semantic system is more sensitive to damage in the left compared to the right ATL, which is in line with theories that attribute a more prominent role to the left ATL due to connections with pre-semantic verbal regions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Temporal lobe volumes in patients with hippocampal sclerosis with or without cortical dysplasia.

PubMed

Diehl, B; Najm, I; LaPresto, E; Prayson, R; Ruggieri, P; Mohamed, A; Ying, Z; Lieber, M; Babb, T; Bingaman, W; Lüders, H O

2004-05-25

Recent MRI-based volume reconstruction studies in intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) suggested atrophy that extends to the adjacent neocortical areas. To study the extent of temporal lobe volume (TLV) abnormalities in patients with pathologically confirmed HS (with or without cortical dysplasia [CD]) who underwent anterior temporal lobectomy for the treatment of drug-resistant TLE. Fifty patients (right TLE: n = 24; left TLE: n = 26) were found to have HS (hippocampal cell loss of >30%). Associated neocortical CD was seen in 20 patients (43%). MRI-based TLVs and hippocampal and hemispheric volume reconstructions in all patients were compared between pathologic groups and with volumes acquired from 10 age-matched control subjects. TLVs ipsilateral to the epileptogenic zone in patients with TLE were smaller than TLVs in control subjects (p < 0.01). In patients with left TLE, TLVs ipsilateral to the epileptogenic zone were smaller than contralateral TLVs (left: 66.6 +/- 8.3 cm3, right: 74.9 +/- 10.0 cm3; p < 0.001). In patients with right TLE, there were no significant asymmetries. The contralateral TLVs (regardless of the side of surgery) were smaller in the HS + CD group than the HS group (HS + CD group: 74.9 +/- 8.6 cm3, HS group: 79.7 +/- 6.6 cm3; p < 0.05). Patients with HS + CD had a tendency to have less hippocampal atrophy and slightly smaller TLVs ipsilateral to the epileptogenic zone, accounting for significantly smaller TLV/hippocampal volume ratios compared with patients with HS alone. Drug-resistant TLE due to HS is associated with extrahippocampal temporal lobe atrophy. The presence of bilateral temporal lobe atrophy is suggestive of a more widespread (bilateral) temporal lobe involvement in patients with HS and CD.

Ictal SPECT using an attachable automated injector: clinical usefulness in the prediction of ictal onset zone.

PubMed

Lee, Jung-Ju; Lee, Sang Kun; Choi, Jang Wuk; Kim, Dong-Wook; Park, Kyung Il; Kim, Bom Sahn; Kang, Hyejin; Lee, Dong Soo; Lee, Seo-Young; Kim, Sung Hun; Chung, Chun Kee; Nam, Hyeon Woo; Kim, Kwang Ki

2009-12-01

Ictal single-photon emission computed tomography (SPECT) is a valuable method for localizing the ictal onset zone in the presurgical evaluation of patients with intractable epilepsy. Conventional methods used to localize the ictal onset zone have problems with time lag from seizure onset to injection. To evaluate the clinical usefulness of a method that we developed, which involves an attachable automated injector (AAI), in reducing time lag and improving the ability to localize the zone of seizure onset. Patients admitted to the epilepsy monitoring unit (EMU) between January 1, 2003, and June 30, 2008, were included. The definition of ictal onset zone was made by comprehensive review of medical records, magnetic resonance imaging (MRI), data from video electroencephalography (EEG) monitoring, and invasive EEG monitoring if available. We comprehensively evaluated the time lag to injection and the image patterns of ictal SPECT using traditional visual analysis, statistical parametric mapping-assisted, and subtraction ictal SPECT coregistered to an MRI-assisted means of analysis. Image patterns were classified as localizing, lateralizing, and nonlateralizing. The whole number of patients was 99: 48 in the conventional group and 51 in the AAI group. The mean (SD) delay time to injection from seizure onset was 12.4+/-12.0 s in the group injected by our AAI method and 40.4+/-26.3 s in the group injected by the conventional method (P=0.000). The mean delay time to injection from seizure detection was 3.2+/-2.5 s in the group injected by the AAI method and 21.4+/-9.7 s in the group injected by the conventional method (P=0.000). The AAI method was superior to the conventional method in localizing the area of seizure onset (36 out of 51 with AAI method vs. 21 out of 48 with conventional method, P=0.009), especially in non-temporal lobe epilepsy (non-TLE) patients (17 out of 27 with AAI method vs. 3 out of 13 with conventional method, P=0.041), and in lateralizing the seizure onset hemisphere (47 out of 51 with AAI method vs. 33 out of 48 with conventional method, P=0.004). The AAI method was superior to the conventional method in reducing the time lag of tracer injection and in localizing and lateralizing the ictal onset zone, especially in patients with non-TLE.

Childhood onset temporal lobe epilepsy: Beyond hippocampal sclerosis.

PubMed

Mühlebner, Angelika; Breu, Markus; Kasprian, Gregor; Schmook, Maria T; Stefanits, Harald; Scholl, Theresa; Samueli, Sharon; Gröppel, Gudrun; Dressler, Anastasia; Prayer, Daniela; Czech, Thomas; Hainfellner, Johannes A; Feucht, Martha

2016-03-01

Hippocampal Sclerosis (HS) is widely recognized as a significant underlying cause of drug-resistant temporal lobe epilepsy (TLE) in adults. In contrast, HS is a rare finding in pediatric surgical series, and a higher incidence of HS associated with cortical dysplasia (i.e. FCD type IIIa according to the new ILAE classification) than in adult series has been reported. Data about the electro-clinical characteristics of this subgroup are scarce. We studied 15 children and adolescents with drug-resistant TLE and HS who had anterior temporal lobe resection at our center with regard to electroclinical characteristics, MRI features and histopathology. Children in whom histopathology was consistent with Focal Cortical Dysplasia (FCD) type IIIa (n = 7) were compared with those who had HS only (n = 8). Clinical characteristics associated with this highly selective subset of patients with FCD type IIIa were: the presence of febrile seizures during infancy, a shorter duration of active epilepsy and a lower age at epilepsy surgery. In addition, there were non-significant trends towards more extended abnormalities on both EEG and neuroimaging. We were, however, not able to find group differences with respect to neuropathologic subtyping of the HS. We present the first detailed description and comprehensive data analysis of children with FCD type IIIa. According to our results, this patient group seems to show a distinct clinical phenotype. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Amygdala Volumetry in Patients with Temporal Lobe Epilepsy and Normal Magnetic Resonance Imaging

PubMed Central

Singh, Paramdeep; Kaur, Rupinderjeet; Saggar, Kavita; Singh, Gagandeep; Aggarwal, Simmi

2016-01-01

Summary Background It has been suggested that the pathophysiology of temporal lobe epilepsy may relate to abnormalities in various brain structures, including the amygdala. Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NMRI) represent a challenge for diagnosis of the underlying abnormality and for presurgical evaluation. To date, however, only few studies have used quantitative structural Magnetic Resonance Imaging-based techniques to examine amygdalar pathology in these patients. Material/Methods Based on clinical examination, 24-hour video EEG recordings and MRI findings, 50 patients with EEG lateralized TLE and normal structural Magnetic Resonance Imaging results were included in this study. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas and hippocampi were conducted in 50 non-epileptic controls (age 7–79 years) and 50 patients with MTLE with normal MRI on a 1.5-Tesla scanner. Visual assessment and amygdalar volumetry were performed on oblique coronal T2W and T1W MP-RAGE images respectively. The T2 relaxation times were measured using the 16-echo Carr-Purcell-Meiboom-Gill sequence (TE, 22–352). Volumetric data were normalized for variation in head size between individuals. Results were assessed by SSPS statistic program. Results Individual manual volumetric analysis confirmed statistically significant amygdala enlargement (AE) in eight (16%) patients. Overall, among all patients with AE and a defined epileptic focus, 7 had predominant increased volume ipsilateral to the epileptic focus. The T2 relaxometry demonstrated no hyperintense signal of the amygdala in any patient with significant AE. Conclusions This paper presented AE in a few patients with TLE and normal MRI. These findings support the hypothesis that there might be a subgroup of patients with MTLE-NMRI in which the enlarged amygdala could be related to the epileptogenic process. PMID:27231493

Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.

PubMed

Lee, Hyoin; Jung, Seungmoon; Lee, Peter; Jeong, Yong

2017-10-01

The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition. Accordingly, recent studies with patients with TLE using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that alterations of resting-state functional connectivity (rsFC) during the chronic period are associated with some clinical manifestations, including learning and memory impairments, emotional instability, and social behavior deficits, in addition to repetitive seizure episodes. In contrast, the changes in the intrinsic rsFC during epileptogenesis, particularly during the latent period, remain unclear. In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We found a decrease in the interhemispheric rsFC at the frontal and temporal regions during both the latent and chronic periods. Furthermore, a significant decrease in the interhemispheric rsFC was observed in the somatosensory area during the chronic period. Changes in network configurations during epileptogenesis were examined by graph theoretical network analysis. Interestingly, increase in the power of low frequency oscillations was observed during the latent period. These results suggest that, even if there are no apparent ictal seizure events during the latent period, there are ongoing changes in the rsFC in the epileptic brain. Furthermore, these results suggest that the pathophysiology of epilepsy may be related to widespread altered intrinsic functional connectivity. These findings can help enhance our understanding of epileptogenesis, and accordingly, changes in intrinsic functional connectivity can serve as an early diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Characteristics of Resting-State Functional Connectivity in Intractable Unilateral Temporal Lobe Epilepsy Patients with Impaired Executive Control Function

PubMed Central

Zhang, Chao; Yang, Hongyu; Qin, Wen; Liu, Chang; Qi, Zhigang; Chen, Nan; Li, Kuncheng

2017-01-01

Executive control function (ECF) deficit is a common complication of temporal lobe epilepsy (TLE). Characteristics of brain network connectivity in TLE with ECF dysfunction are still unknown. The aim of this study was to investigate resting-state functional connectivity (FC) changes in patients with unilateral intractable TLE with impaired ECF. Forty right-handed patients with left TLE confirmed by comprehensive preoperative evaluation and postoperative pathological findings were enrolled. The patients were divided into normal ECF (G1) and decreased ECF (G2) groups according to whether they showed ECF impairment on the Wisconsin Card Sorting Test (WCST). Twenty-three healthy volunteers were recruited as the healthy control (HC) group. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI). Group-information-guided independent component analysis (GIG-ICA) was performed to estimate resting-state networks (RSNs) for all subjects. General linear model (GLM) was employed to analyze intra-network FC (p < 0.05, false discovery rate, FDR correction) and inter-network FC (p < 0.05, Bonferroni correction) of RSN among three groups. Pearson correlations between FC and neuropsychological tests were also determined through partial correlation analysis (p < 0.05). Eleven meaningful RSNs were identified from 40 left TLE and 23 HC subjects. Comparison of intra-network FC of all 11 meaningful RSNs did not reveal significant difference among the three groups (p > 0.05, FDR correction). For inter-network analysis, G2 exhibited decreased FC between the executive control network (ECN) and default-mode network (DMN) when compared with G1 (p = 0.000, Bonferroni correction) and HC (p = 0.000, Bonferroni correction). G1 showed no significant difference of FC between ECN and DMN when compared with HC. Furthermore, FC between ECN and DMN had significant negative correlation with perseverative responses (RP), response errors (RE) and perseverative errors (RPE) and had significant positive correlation categories completed (CC) in both G1 and G2 (p < 0.05). No significant difference of Montreal Cognitive Assessment (MoCA) was found between G1 and G2, while intelligence quotient (IQ) testing showed significant difference between G1and G2.There was no correlation between FC and either MoCA or IQ performance. Our findings suggest that ECF impairment in unilateral TLE is not confined to the diseased temporal lobe. Decreased FC between DMN and ECN may be an important characteristic of RSN in intractable unilateral TLE. PMID:29375338

Neuroimaging correlates of language network impairment and reorganization in temporal lobe epilepsy

PubMed Central

Balter, S.; Lin, G.; Leyden, K.M.; Paul, B.M.; McDonald, C.R.

2016-01-01

Advanced, noninvasive imaging has revolutionized our understanding of language networks in the brain and is reshaping our approach to the presurgical evaluation of patients with epilepsy. Functional magnetic resonance imaging (fMRI) has had the greatest impact, unveiling the complexity of language organization and reorganization in patients with epilepsy both pre- and postoperatively, while volumetric MRI and diffusion tensor imaging have led to a greater appreciation of structural and microstructural correlates of language dysfunction in different epilepsy syndromes. In this article, we review recent literature describing how unimodal and multimodal imaging has advanced our knowledge of language networks and their plasticity in epilepsy, with a focus on the most frequently studied epilepsy syndrome in adults, temporal lobe epilepsy (TLE). We also describe how new analytic techniques (i.e., graph theory) are leading to a refined characterization of abnormal brain connectivity, and how subject-specific imaging profiles combined with clinical data may enhance the prediction of both seizure and language outcomes following surgical interventions. PMID:27393391

Lateralization of Temporal Lobe Epilepsy using a Novel Uncertainty Analysis of MR Diffusion in Hippocampus, Cingulum, and Fornix, and Hippocampal Volume and FLAIR Intensity

PubMed Central

Nazem-Zadeh, Mohammad-Reza; Schwalb, Jason M.; Elisevich, Kost V.; Bagher-Ebadian, Hassan; Hamidian, Hajar; Akhondi-Asl, Ali-Reza; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid

2014-01-01

Purpose To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. Methods We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extra-operative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. Results HVU was estimated to be 3.1 × 10−5 for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating lateralization results of HVU analysis on these quantities by majority voting detected the epileptogenic side for 19 out of 20 cases with no wrong lateralization. Conclusion The presence of MTS in TLE patients is associated with an elevated MD value in the ipsilateral hippocampus and a reduced FA value in the posteroinferior subregion of the ipsilateral cingulum and crus of ipsilateral fornix. When considering all TLE patients, among the mentioned biomarkers the hippocampal MD had the best performance with true detection rate of 90% without any wrong lateralization. The proposed uncertainty based analyses hold promise for improving decision-making for surgical resection. PMID:24857759

Long-Term Electroclinical and Employment Follow up in Temporal Lobe Epilepsy Surgery. A Cuban Comprehensive Epilepsy Surgery Program

PubMed Central

Garcia Maeso, Ivan; Baez Martin, Margarita M.; Bender del Busto, Juan E.; García Navarro, María Eugenia; Quintanal Cordero, Nelson; Estupiñan Díaz, Bárbara; Lorigados Pedre, Lourdes; Valdés Yerena, Ricardo; Gonzalez, Judith; Garbey Fernandez, Randy; Sánchez Coroneux, Abel

2018-01-01

The purpose of this paper is to present a long- term electroclinical and employment follow up in temporal lobe epilepsy (TLE) patients in a comprehensive epilepsy surgery program. Forty adult patients with pharmacoresistant TLE underwent detailed presurgical evaluation. Electroencephalogram (EEG) and clinical follow up assessment for each patient were carried out. The occurrence of interictal epileptiform activity (IEA) and absolute spike frequency (ASF) were tabulated before and after 1, 6, 12, 24 and 72 months surgical treatment. Employment status pre- to post-surgery at the last evaluated period was also examined. Engel scores follow-up was described as follows: at 12 months 70% (28) class I, 10% (4) class II and 19% (8) class III-IV; at 24 months after surgery 55.2% (21) of the patients were class I, 28.9% (11) class II and 15.1% (6) class III-IV. After one- year follow up 23 (57.7%) patients were seizure and aura-free (Engel class IA). These figures changed to 47.3%, and 48.6% respectively two and five years following surgery whereas 50% maintained this condition in the last follow up period. A decline in the ASF was observed from the first year until the sixth year after surgery in relation to the preoperative EEG. The ASF one year after surgery allowed to distinguish “satisfactory” from “unsatisfactory” seizure relief outcome at the last follow up. An adequate social functioning in terms of education and employment in more than 50% of the patients was also found. Results revealed the feasibility of conducting a successful epilepsy surgery program with favorable long term electroclinical and psychosocial functioning outcomes in a developing country as well. PMID:29389846

Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

PubMed

Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K; Bernick, Charles; Ghosh, Chaitali; Rapp, Edward; Bazarian, Jeffrey J; Janigro, Damir

2016-01-01

Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. Copyright © 2015 Elsevier B.V. All rights reserved.

Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy

PubMed Central

Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj; Brennan, Chanda; Schreiber, Peter; Dadas, Aaron; Bahrami, Ashkon; Solanki, Jesal; Bandyopadhyay, Anasua; Morris, Jacqueline K.; Bernick, Charles; Ghosh, Chaitali; Bazarian, Jeffrey J.; Janigro, Damir

2016-01-01

Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six post mortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE. PMID:26556772

Study on the Relationships between Intrinsic Functional Connectivity of the Default Mode Network and Transient Epileptic Activity

PubMed Central

Lopes, Renaud; Moeller, Friederike; Besson, Pierre; Ogez, François; Szurhaj, William; Leclerc, Xavier; Siniatchkin, Michael; Chipaux, Mathilde; Derambure, Philippe; Tyvaert, Louise

2014-01-01

Rationale: Simultaneous recording of electroencephalogram and functional MRI (EEG–fMRI) is a powerful tool for localizing epileptic networks via the detection of hemodynamic changes correlated with interictal epileptic discharges (IEDs). fMRI can be used to study the long-lasting effect of epileptic activity by assessing stationary functional connectivity during the resting-state period [especially, the connectivity of the default mode network (DMN)]. Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) are associated with low responsiveness and disruption of DMN activity. A dynamic functional connectivity approach might enable us to determine the effect of IEDs on DMN connectivity and to better understand the correlation between DMN connectivity changes and altered consciousness. Method: We studied dynamic changes in DMN intrinsic connectivity and their relation to IEDs. Six IGE patients (with generalized spike and slow-waves) and 6 TLE patients (with unilateral left temporal spikes) were included. Functional connectivity before, during, and after IEDs was estimated using a sliding window approach and compared with the baseline period. Results: No dependence on window size was observed. The baseline DMN connectivity was decreased in the left hemisphere (ipsilateral to the epileptic focus) in TLEs and was less strong but remained bilateral in IGEs. We observed an overall increase in DMN intrinsic connectivity prior to the onset of IEDs in both IGEs and TLEs. After IEDs in TLEs, we found that DMN connectivity increased before it returned to baseline values. Most of the DMN regions with increased connectivity before and after IEDs were lateralized to the left hemisphere in TLE (i.e., ipsilateral to the epileptic focus). Conclusion: Results suggest that DMN connectivity may facilitate IED generation and may be affected at the time of the IED. However, these results need to be confirmed in a larger independent cohort. PMID:25346721

Clinical utility of the Wechsler Memory Scale--Fourth Edition (WMS-IV) in predicting laterality of temporal lobe epilepsy among surgical candidates.

PubMed

Soble, Jason R; Eichstaedt, Katie E; Waseem, Hena; Mattingly, Michelle L; Benbadis, Selim R; Bozorg, Ali M; Vale, Fernando L; Schoenberg, Mike R

2014-12-01

This study evaluated the accuracy of the Wechsler Memory Scale--Fourth Edition (WMS-IV) in identifying functional cognitive deficits associated with seizure laterality in localization-related temporal lobe epilepsy (TLE) relative to a previously established measure, the Rey Auditory Verbal Learning Test (RAVLT). Emerging WMS-IV studies have highlighted psychometric improvements that may enhance its ability to identify lateralized memory deficits. Data from 57 patients with video-EEG-confirmed unilateral TLE who were administered the WMS-IV and RAVLT as part of a comprehensive presurgical neuropsychological evaluation for temporal resection were retrospectively reviewed. We examined the predictive accuracy of the WMS-IV not only in terms of verbal versus visual composite scores but also using individual subtests. A series of hierarchal logistic regression models were developed, including the RAVLT, WMS-IV delayed subtests (Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction), and a WMS-IV verbal-visual memory difference score. Analyses showed that the RAVLT significantly predicted laterality with overall classification rates of 69.6% to 70.2%, whereas neither the individual WMS-IV subtests nor the verbal-visual memory difference score accounted for additional significant variance. Similar to previous versions of the WMS, findings cast doubt as to whether the WMS-IV offers significant incremental validity in discriminating seizure laterality in TLE beyond what can be obtained from the RAVLT. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in regional homogeneity of baseline brain activity in pediatric temporal lobe epilepsy.

PubMed

Mankinen, Katariina; Long, Xiang-Yu; Paakki, Jyri-Johan; Harila, Marika; Rytky, Seppo; Tervonen, Osmo; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka; Rantala, Heikki; Zang, Yu-Feng; Kiviniemi, Vesa

2011-02-10

Recent findings on intracortical EEG measurements show that the synchrony of localized neuronal networks is altered in epileptogenesis, leading to generalized seizure activity via connector hubs in the neuronal networks. Regional homogeneity (ReHo) analysis of blood oxygen level-dependent (BOLD) signals has demonstrated localized signal synchrony and disease-related alterations in a number of instances. We wanted to find out whether the ReHo of resting-state activity can be used to detect regional signal synchrony alterations in children with non-lesional temporal lobe epilepsy (TLE). Twenty-one TLE patients were compared with age and gender-matched healthy controls. Significantly increased ReHo was discovered in the posterior cingulate gyrus and the right medial temporal lobe of the patients, and they also had significantly decreased ReHo in the cerebellum compared with the healthy controls. However, the alterations in ReHo differed between the patients with normal and abnormal interictal EEGs, the latter showing significantly increased ReHo in the right fusiform gyrus and significantly decreased ReHo in the right medial frontal gyrus relative to the controls, while those with normal EEGs had significantly increased ReHo in the right inferior temporal gyrus and the left posterior cingulate gyrus. We conclude that altered BOLD signal synchrony can be detected in the cerebral and cerebellar cortices of children with TLE even in the absence of interictal EEG abnormalities. Copyright © 2010 Elsevier B.V. All rights reserved.

Inhibition of mTOR Pathway by Rapamycin Decreases P-glycoprotein Expression and Spontaneous Seizures in Pharmacoresistant Epilepsy.

PubMed

Chi, Xiaosa; Huang, Cheng; Li, Rui; Wang, Wei; Wu, Mengqian; Li, Jinmei; Zhou, Dong

2017-04-01

The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin. Non-responders were treated for 4 weeks with vehicle only or with the mTOR pathway inhibitor rapamycin at doses of 1, 3, and 6 mg/kg. Western blotting and immunohistochemistry were used to detect the expression of phospho-S6 (P-S6) and P-gp at different time points (1 h, 8 h, 1 day, 3 days, 1 weeks, 2 weeks, and 4 weeks) after the onset of treatment. Overexpression of P-S6 and P-gp was detected in both refractory mTLE patients and non-responder rats. Rapamycin showed an inhibitory effect on P-S6 and P-gp expression 1 week after treatment in rats. In addition, the expression levels of P-S6 and P-gp in the 6 mg/kg group were significantly lower than those in the 1 mg/kg or the 3 mg/kg group at the same time points (all P < 0.05). Moreover, rapamycin decreased the duration and number of CL-induced seizures, as well as the stage of non-responders (all P < 0.05). The current study indicates that the mTOR signaling pathway plays a critical role in P-gp expression in drug-resistant epilepsy. Inhibition of the mTOR pathway by rapamycin may be a potential therapeutic approach for pharmacoresistant epilepsy.

Confident Surgical Decision Making in Temporal Lobe Epilepsy by Heterogeneous Classifier Ensembles

PubMed Central

Fakhraei, Shobeir; Soltanian-Zadeh, Hamid; Jafari-Khouzani, Kourosh; Elisevich, Kost; Fotouhi, Farshad

2015-01-01

In medical domains with low tolerance for invalid predictions, classification confidence is highly important and traditional performance measures such as overall accuracy cannot provide adequate insight into classifications reliability. In this paper, a confident-prediction rate (CPR) which measures the upper limit of confident predictions has been proposed based on receiver operating characteristic (ROC) curves. It has been shown that heterogeneous ensemble of classifiers improves this measure. This ensemble approach has been applied to lateralization of focal epileptogenicity in temporal lobe epilepsy (TLE) and prediction of surgical outcomes. A goal of this study is to reduce extraoperative electrocorticography (eECoG) requirement which is the practice of using electrodes placed directly on the exposed surface of the brain. We have shown that such goal is achievable with application of data mining techniques. Furthermore, all TLE surgical operations do not result in complete relief from seizures and it is not always possible for human experts to identify such unsuccessful cases prior to surgery. This study demonstrates the capability of data mining techniques in prediction of undesirable outcome for a portion of such cases. PMID:26609547

Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy

PubMed Central

Malheiros, Jackeline M.; Polli, Roberson S.; Paiva, Fernando F.; Longo, Beatriz M.; Mello, Luiz E.; Silva, Afonso C.; Tannús, Alberto; Covolan, Luciene

2012-01-01

Summary Purpose Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese-enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well-established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE). Methods To modulate MFS, cycloheximide (CHX), a protein synthesis inhibitor, was co-administered with Pilo in a sub-group of animals. In vivo MEMRI was performed 3 months after induction of SE and compared to the neo-Timm histological labeling of zinc mossy fiber terminals in the dentate gyrus (DG). Key findings Chronically epileptic rats displaying MFS as detected by neo-Timm histology had a hyperintense MEMRI signal in the DG, while chronically epileptic animals that did not display MFS had minimal MEMRI signal enhancement compared to non-epileptic control animals. A strong correlation (r = 0.81, P<0.001) was found between MEMRI signal enhancement and MFS. Significance This study shows that MEMRI is an attractive non-invasive method to detect mossy fiber sprouting in vivo and can be used as an evaluation tool in testing therapeutic approaches to manage chronic epilepsy. PMID:22642664

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PubMed

Koubeissi, Mohamad Z; Kahriman, Emine; Fastenau, Philip; Bailey, Christopher; Syed, Tanvir; Amina, Shahram; Miller, Jonathan; Munyon, Charles; Tanner, Adriana; Karanec, Kristina; Tuxhorn, Ingrid; Lüders, Hans

2016-05-01

The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced sensitivity of the N400 and late positive component to semantic congruity and word repetition in left temporal lobe epilepsy.

PubMed

Olichney, John M; Riggins, Brock R; Hillert, Dieter G; Nowacki, Ralph; Tecoma, Evelyn; Kutas, Marta; Iragui, Vicente J

2002-07-01

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% "congruous" (category exemplars) and 50% "incongruous" (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from approximately 10-140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

Severe intermittent anxiety attacks. A diagnosis challenge in temporal lobe epilepsy.

PubMed

Alshomrani, Abdulaziz T; Zaidan, Radwan M; Abdulmalik, Yosef T; Alrahili, Nader M

2017-01-01

Psychiatric symptoms are frequently reported with epilepsy. Anxiety symptoms are the most common psychiatric expressions of temporal lobe epilepsy (TLE). Longer duration of the epileptic manifestation can be mistaken for psychiatric diseases, particularly when psychiatric symptoms are the only manifestations of the disorder. Here we introduce a case of a 27-year-old Saudi man presented to our clinic with a history of sudden and severe anxiety attacks over the prior 2 years, each lasting for 2-3 days. The attacks recurred monthly without clear triggers, and he recovered his normal clinical state between them. His condition worsened with antidepressants and improved with antiepileptic. Later follow ups and work ups supported the diagnosis of temporal lobe epilepsy. Diagnosis after such presentation may be challenging and we tried, in this case, to enhance awareness of such an unusual presentation.

Neuropsychologist's (re-)view: Resective versus ablative amygdalohippocampectomies.

PubMed

Witt, Juri-Alexander; Hoppe, Christian; Helmstaedter, Christoph

2018-05-01

Pharmacoresistant mesial temporal lobe epilepsy (mTLE) represents the major indication for epilepsy surgery. Since epilepsy surgery is an elective treatment option, preserving cognition is a high priority. Given the essential role of temporomesial structures in declarative long-term memory formation, surgical treatment for mTLE is primarily associated with a risk of material-specific memory decline, but other cognitive domains may be affected as well. The major determinants for the neuropsychological outcome are the functional integrity of surgically affected tissues, the functional reserve capacities of the remnant brain, the postoperative seizure outcome, as well as the quantitative and qualitative changes of antiepileptic drugs. Anterior temporal lobectomy has long been the standard procedure for treating mTLE. However, if an exclusive mesial pathology is present, then functional non-pathological tissues of the temporal pole and neocortex are sacrificed. As a result, more selective or tailored surgical approaches have been developed which strive towards minimizing iatrogenic effects. However, whether or not these approaches are equipotential with regard to seizure control is still a matter of debate. The quality of the presurgical diagnostics could also be decisive. Selective surgery should indeed be selective in terms of preventing evitable collateral cortical damage along the approach. Invasivity and risks of collateral damage associated with "open" selective resective surgery are further minimized by stereotactic ablative surgery via thermocoagulation, or eventually even eliminated by gamma knife surgery. From a neuropsychological point of view, this development is consequent and desirable, but no clear scientific evidence of a superior cognitive outcome after radiosurgery or thermocoagulation currently exists. The studies that are available contain significant methodological limitations. Thus, randomized head-to-head cognitive outcome studies of competing selective procedures are needed, which should meet the minimum requirements for study design and neuropsychological evaluations. Finally, none of the surgical treatment variants can systematically prevent memory decline when the hippocampus is targeted. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy.

PubMed

Liu, Anli; Bryant, Andrew; Jefferson, Ashlie; Friedman, Daniel; Minhas, Preet; Barnard, Sarah; Barr, William; Thesen, Thomas; O'Connor, Margaret; Shafi, Mouhsin; Herman, Susan; Devinsky, Orrin; Pascual-Leone, Alvaro; Schachter, Steven

2016-02-01

Depression and memory dysfunction significantly impact the quality of life of patients with epilepsy. Current therapies for these cognitive and psychiatric comorbidities are limited. We explored the efficacy and safety of transcranial direct current stimulation (TDCS) for treating depression and memory dysfunction in patients with temporal lobe epilepsy (TLE). Thirty-seven (37) adults with well-controlled TLE were enrolled in a double-blinded, sham-controlled, randomized, parallel-group study of 5 days of fixed-dose (2 mA, 20 min) TDCS. Subjects were randomized to receive either real or sham TDCS, both delivered over the left dorsolateral prefrontal cortex. Patients received neuropsychological testing and a 20-minute scalp EEG at baseline immediately after the TDCS course and at 2- and 4-week follow-up. There was improvement in depression scores immediately after real TDCS, but not sham TDCS, as measured by changes in the Beck Depression Inventory (BDI change: -1.68 vs. 1.27, p<0.05) and NDDI-E (-0.83 vs. 0.9091, p=0.05). There was no difference between the groups at the 2- or 4-week follow-up. There was no effect on delayed or working memory performance. Transcranial direct current stimulation was well-tolerated and did not increase seizure frequency or interictal discharge frequency. Transcranial direct current stimulation induced an increase in delta frequency band power over the frontal region and delta, alpha, and theta band power in the occipital region after real stimulation compared to sham stimulation, although the difference did not reach statistical significance. This study provides evidence for the use of TDCS as a safe and well-tolerated nonpharmacologic approach to improving depressive symptoms in patients with well-controlled TLE. However, there were no changes in memory function immediately following or persisting after a stimulation course. Further studies may determine optimal stimulation parameters for maximal mood benefit. Copyright © 2015. Published by Elsevier Inc.

Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study.

PubMed

Nakayama, Yoko; Masuda, Hiroshi; Shirozu, Hiroshi; Ito, Yosuke; Higashijima, Takefumi; Kitaura, Hiroki; Fujii, Yukihiko; Kakita, Akiyoshi; Fukuda, Masafumi

2017-09-01

It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. There was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm 3 ; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10× -4 number of neurons/μm 2 ; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala. Copyright © 2017 Elsevier B.V. All rights reserved.

Does unilateral insular resection disturb personality? A study with epileptic patients.

PubMed

Hébert-Seropian, Benjamin; Boucher, Olivier; Sénéchal, Carole; Rouleau, Isabelle; Bouthillier, Alain; Lepore, Franco; Nguyen, Dang Khoa

2017-09-01

The insula is now regarded as a potential site of epileptogenesis in drug-resistant epilepsy, and the advent of microsurgical techniques has allowed insular cortectomy to become a treatment of choice when the insular cortex is involved in the seizure focus. However, considering the evidence of an insular role in socio-emotional processing, it remains unknown whether these cortical resections disturb personality and social behavior as experienced in daily life. We examined such changes in a group of patients (n=19) who underwent epilepsy surgery involving partial or complete resection of the insula, and compared them to a group of patients who underwent standard temporal lobe epilepsy (TLE) surgery (n=19) as a lesion-control group. Participants were assessed on the Iowa Scales of Personality Change, filled by a close relative at least six months after surgery. While postoperative changes did not significantly differ between groups on any of the ISPC items, insular resections were associated with mild but significant increases in irritability, emotional lability, anxiety, and frugality postoperatively, which, apart from anxiety, were not significant among TLE patients. Our results are congruent with the idea that the insula contributes to emotion processing. To our knowledge, this study is the first to systematically assess personality changes in a consecutive sample of patients with insular resections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of protease-activated receptor 1 inhibition on anxiety and fear following status epilepticus.

PubMed

Bogovyk, Ruslan; Lunko, Oleksii; Fedoriuk, Mihail; Isaev, Dmytro; Krishtal, Oleg; Holmes, Gregory L; Isaeva, Elena

2017-02-01

Protease-activated receptor 1 (PAR1) is an important contributor to the pathogenesis of a variety of brain disorders associated with a risk of epilepsy development. Using the lithium-pilocarpine model of temporal lobe epilepsy (TLE), we recently showed that inhibition of this receptor during the first ten days after pilocarpine-induced status epilepticus (SE) results in substantial anti-epileptogenic and neuroprotective effects. As PAR1 is expressed in the central nervous system regions of importance for processing emotional reactions, including amygdala and hippocampus, and TLE is frequently associated with a chronic alteration of the functions of these regions, we tested the hypothesis that PAR1 inhibition could modulate emotionally driven behavioral responses of rats experiencing SE. We showed that SE induces a chronic decrease in the animals' anxiety-related behavior and an increase of locomotor activity. PAR1 inhibition after SE abolished the alteration of the anxiety level but does not affect the increase of locomotor activity in the open field and elevated plus maze tests. Moreover, while PAR1 inhibition produces an impairment of memory recall in the context fear conditioning paradigm in the control group, it substantially improves contextual and cued fear learning in rats experiencing SE. These data suggest that PAR1-dependent signaling is involved in the mechanisms underlying emotional disorders in epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Touching the void - First and third person perspectives in two cases of autobiographical amnesia linked to temporal lobe epilepsy.

PubMed

Zeman, Adam; Byruck, Marcus; Tallis, Peter; Vossel, Keith; Tranel, Daniel

2018-02-01

Temporal lobe epilepsy (TLE) can be associated with a marked impairment of autobiographical memory. This is occasionally its presenting feature. We describe two individuals with severe epilepsy-associated autobiographical memory loss. Both MB and PT were reassured initially that their memory was intact on the basis of standard neuropsychological tests. Both have written detailed accounts of their symptoms. The key neuropsychological features of their cases are the relative normality of performance on standard memory tests, with preservation of semantic memory for impersonal information, in contrast to a profound amnesia for salient autobiographical episodes and an impoverishment of imaginative scene construction. First person accounts from these individuals illustrate the importance of autobiographical memory in sustaining a coherent sense of self, informing interpersonal relationships and supporting future thinking and problem-solving. These cases contribute to the growing evidence for a distinctive pattern of autobiographical memory loss associated with TLE, and indicate that it can take a severe form affecting both personal semantics and episodic recollection. Defining the phase of memory processing most relevant to this form of amnesia, and the roles of physiological and structural pathology, requires further research. The paper's title refers to the introspective 'void' highlighted by both MB and PT in their reports - in PT's words: 'My primary symptom is the void that is my past'. Copyright © 2017. Published by Elsevier Ltd.

Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice

PubMed Central

Smeland, Olav B; Hadera, Mussie G; McDonald, Tanya S; Sonnewald, Ursula; Borges, Karin

2013-01-01

Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine–status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5–4 weeks after SE with [1,2-13C]glucose before microwave fixation of the head. Using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography—mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and 13C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine–SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in 13C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced 13C labeling of glutamate, glutamine and aspartate via the pyruvate carboxylation and pyruvate dehydrogenation pathways, suggesting slower turnover of these amino acids and/or the TCA cycle. In conclusion, mitochondrial metabolic dysfunction and altered amino-acid metabolism is found in both cortex and HF in this epilepsy model. PMID:23611869

Ictal affective symptoms in temporal lobe epilepsy are related to gender and age.

PubMed

Toth, Vanda; Fogarasi, Andras; Karadi, Kazmer; Kovacs, Norbert; Ebner, Alois; Janszky, Jozsef

2010-07-01

We systematically analyzed the video-recorded and patient-reported, as well as positive and negative ictal affective symptoms (IAS) in temporal lobe epilepsy (TLE). Our aim was to assess (1) frequency, (2) gender effect, (3) lateralizing significance, (4) localizing value, and (5) prognostic significance in epilepsy surgery of IAS in patients with video-registered seizures. We reviewed ictal video recordings of 184 patients (99 women, aged 16-63). All patients had surgery for intractable TLE with video-recorded complex partial seizures (CPS) due to temporal lobe lesions visualized by high-resolution magnetic resonance imaging (MRI). Affective auras (AAs) were categorized into two groups: positive or negative. We registered AAs in 18% of patients: positive in 3%, negative in 15%. We saw ictal affective behavior (IAB) in 22% of patients; 10% had positive, whereas 14% had negative IAB. Two patients had both positive and negative IAB. AAs showed an association with IAB in case of fear expression versus fear auras (p = 0.018). IAB, especially negative IAB, occurred more often in women than in men. Patients with negative IAB were younger than others. We could not demonstrate an association between IAS and the localization, lateralization, or hemispheric dominance. Surgical outcome did not associate with IAS. Patient-reported and video-recorded negative-but not positive-affective signs are related to each other. Video-recorded negative AAs occur more often in women and young patients.

The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats.

PubMed

Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad

2016-01-01

Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress.

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

PubMed Central

Sanz-García, Ancor; Vega-Zelaya, Lorena; Pastor, Jesús; Torres, Cristina V.; Sola, Rafael G.; Ortega, Guillermo J.

2016-01-01

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area. PMID:28060326

Parahippocampectomy as a New Surgical Approach to Mesial Temporal Lobe Epilepsy Caused By Hippocampal Sclerosis: A Pilot Randomized Comparative Clinical Trial.

PubMed

Alonso-Vanegas, Mario Arturo; Freire Carlier, Iván D; San-Juan, Daniel; Martínez, Alma Rosa; Trenado, Carlos

2018-02-01

The parahippocampal gyrus plays an important role in the epileptogenic pathways of mesial temporal lobe epilepsy caused by hippocampal sclerosis (mTLE-HS); its resection could prevent epileptic seizures with fewer complications. This study evaluates the initial efficacy and safety of anterior temporal lobectomy (ATL), selective amygdalohipppocampectomy (SAH), and parahippocampectomy (PHC) surgical approaches in mTLE-HS. A randomized comparative pilot clinical trial (2008-2011) was performed that included patients with mTLE-HS who underwent ATL, trans-T3 SAH, and trans-T3 PHC. Their sociodemographic characteristics, visual field profiles, verbal and visual memory profiles, and Engel scale outcome at baseline and at 1 and 5 years are described, using descriptive statistics along with parametric and nonparametric tests. Forty-three patients with a mean age of 35.2 years (18-56 years), 65% female, were analyzed: 14 underwent PHC, 14 ATL, and 15 SAH. The following percentages refer to those patients who were seizure free (Engel class IA) at 1-year and 5-year follow-up, respectively: 42.9% PHC, 71.4% ATL, and 60% SAH (P = 0.304); 28.6% PHC, 50% ATL, and 53.3% SAH (P = 0.353). Postoperative visual field deficits were 0% PHC, 85.7% ATL, and 46.7% SAH (P = 0.001). Verbal and/or visual memory worsening were present in 21.3% PHC, 42.8% ATL, and 33.4% SAH (P = 0.488) and preoperative and postoperative visual memory scores were significantly different in the SAH group only (P = 0.046). PHC, ALT, and SAH show a preliminary similar efficacy in short-term seizure-free rates in patients with mTLE-HS. However, PHC efficacy in the long-term decreases compared with the other surgical techniques. PHC does not produce postoperative visual field deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term outcome characteristics in mesial temporal lobe epilepsy with and without associated cortical dysplasia.

PubMed

Schmeiser, B; Hammen, T; Steinhoff, B J; Zentner, J; Schulze-Bonhage, A

2016-10-01

The intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. Our study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results were evaluated forming two groups: Group A consisted of isolated mesiotemporal lesions. Group B comprised patients with mTLE and additional focal cortical dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival analysis, using log-rank-tests and a multivariate regression model. Postoperative running down phenomenon was defined as seizure freedom after a period of gradual reduction of postoperative seizure frequency. This was compared to patients with ongoing epilepsy. Complete seizure freedom was achieved in 65.0% of investigated patients at 1year and in 56.5% at long-term follow-up of ≥5 years after surgery. Corresponding results were 64.2% and 56.8% at 1 and ≥5 years, respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive for favorable postoperative outcome in the total group were younger age at surgery, shorter duration of epilepsy, absence of secondarily generalized tonic-clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal epileptiform discharges (IEDs), complete resection of the lesion as well as absence of postoperative epileptiform activity and of early postoperative seizures. In subgroup analyses, patients of group A demonstrated longer postoperative seizure-free intervals with adolescent age at surgery, short duration of epilepsy before surgery and absence of SGTCS, whereas in patients of group B ipsilateral temporal seizure onset and strictly unilateral IEDs in EEG as well as complete resection were predictors for favorable seizure outcome. Furthermore, absence of early postoperative seizures and of spikes in EEG were predictive factors for long-term seizure-freedom in both subgroups. The running down phenomenon was found in 33 (7.2%) patients. None of the parameters evaluated demonstrated significant predictive power. Only late seizure onset and neoplastic lesions showed a trend for postoperative gradual seizure reduction in multivariate analyses. Depending on the presence or absence of focal cortical dysplasia in addition to mesiotemporal structural alterations, predictors of long-term seizure control differed regarding the relevant clinical and electrophysiological features. This is important for specific patient counseling in respective groups. Copyright © 2016 Elsevier B.V. All rights reserved.

Material-Specific Lateralization of Working Memory in the Medial Temporal Lobe

ERIC Educational Resources Information Center

Wagner, Dylan D.; Sziklas, Viviane; Garver, Krista E.; Jones-Gotman, Marilyn

2009-01-01

Mnemonic deficits in patients with medial temporal lobe (MTL) damage arising from temporal lobe epilepsy (TLE) are traditionally constrained to long-term episodic memory, sparing short-term and working memory (WM). This view of WM as being independent of MTL structures has recently been challenged by a small number of patient and neuroimaging…

Gray matter structural compromise is equally distributed in left and right temporal lobe epilepsy.

PubMed

Liu, Min; Bernhardt, Boris C; Bernasconi, Andrea; Bernasconi, Neda

2016-02-01

In drug-resistant temporal lobe epilepsy (TLE), MRI studies have shown consistent mesiotemporal and neocortical structural alterations when comparing patients to healthy controls. It remains, however, relatively unclear whether the side of seizure focus differentially impacts the degree of structural damage. This work performed a comprehensive surface-based analysis of mesiotemporal and neocortical morphology on preoperative 1.5 T MRI in 25/35 LTLE/RTLE patients that achieved seizure freedom after surgery (i.e., Engel-I outcome; 7 ± 2 years follow-up), an imaging-independent confirmation of focus lateralization. Compared to 46 age- and sex-matched controls, both TLE groups displayed marked ipsilateral atrophy in mesiotemporal regions, while cortical thinning was bilateral. Direct contrasts between LTLE and RTLE did not reveal significant differences. Bootstrap simulations indicated low reproducibility of observing a between-cohort difference; power analysis revealed that more than 110 patients would be necessary to detect subtle differences. No difference between LTLE and RTLE was confirmed when using voxel-based morphometry, an independent proxy of gray matter volume. Similar results were obtained analyzing a separate 3 T dataset (15/15 LTLE/RTLE patients; Engel-I after 4 ± 2 years follow-up; 42 controls). Our results strongly support equivalent gray matter compromise in left and right TLE. The morphological profile of seizure-free patients, presenting with ipsilateral mesiotemporal and bilateral cortical atrophy, motivates the development of neuromarkers of outcome that consider both mesiotemporal and neocortical structures. Hum Brain Mapp 37:515-524, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Task activation and functional connectivity show concordant memory laterality in temporal lobe epilepsy.

PubMed

Sideman, Noah; Chaitanya, Ganne; He, Xiaosong; Doucet, Gaelle; Kim, Na Young; Sperling, Michael R; Sharan, Ashwini D; Tracy, Joseph I

2018-04-01

In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures. A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures. Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres. Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several different phenotypes, varying according to side of seizure onset and the specific mesial structures involved. There is good correspondence between task LI activation and FC patterns in the setting of LTLE, suggesting that reliable visual episodic memory reorganization may require both a shift in nodal activation and a change in nodal connectivity with mesial temporal structures involved in memory. Copyright © 2018. Published by Elsevier Inc.

Presurgical EEG-fMRI in a complex clinical case with seizure recurrence after epilepsy surgery

PubMed Central

Zhang, Jing; Liu, Qingzhu; Mei, Shanshan; Zhang, Xiaoming; Wang, Xiaofei; Liu, Weifang; Chen, Hui; Xia, Hong; Zhou, Zhen; Li, Yunlin

2013-01-01

Epilepsy surgery has improved over the last decade, but non-seizure-free outcome remains at 10%–40% in temporal lobe epilepsy (TLE) and 40%–60% in extratemporal lobe epilepsy (ETLE). This paper reports a complex multifocal case. With a normal magnetic resonance imaging (MRI) result and nonlocalizing electroencephalography (EEG) findings (bilateral TLE and ETLE, with more interictal epileptiform discharges [IEDs] in the right frontal and temporal regions), a presurgical EEG-functional MRI (fMRI) was performed before the intraoperative intracranial EEG (icEEG) monitoring (icEEG with right hemispheric coverage). Our previous EEG-fMRI analysis results (IEDs in the left hemisphere alone) were contradictory to the EEG and icEEG findings (IEDs in the right frontal and temporal regions). Thus, the EEG-fMRI data were reanalyzed with newly identified IED onsets and different fMRI model options. The reanalyzed EEG-fMRI findings were largely concordant with those of EEG and icEEG, and the failure of our previous EEG-fMRI analysis may lie in the inaccurate identification of IEDs and wrong usage of model options. The right frontal and temporal regions were resected in surgery, and dual pathology (hippocampus sclerosis and focal cortical dysplasia in the extrahippocampal region) was found. The patient became seizure-free for 3 months, but his seizures restarted after antiepileptic drugs (AEDs) were stopped. The seizures were not well controlled after resuming AEDs. Postsurgical EEGs indicated that ictal spikes in the right frontal and temporal regions reduced, while those in the left hemisphere became prominent. This case suggested that (1) EEG-fMRI is valuable in presurgical evaluation, but requires caution; and (2) the intact seizure focus in the remaining brain may cause the non-seizure-free outcome. PMID:23926432

Neurological Disease Rises from Ocean to Bring Model for Human Epilepsy to Life

PubMed Central

Ramsdell, John S.

2010-01-01

Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages. PMID:22069654

Neurological disease rises from ocean to bring model for human epilepsy to life.

PubMed

Ramsdell, John S

2010-07-01

Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages.

Texture analysis of high-resolution FLAIR images for TLE

NASA Astrophysics Data System (ADS)

Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid; Elisevich, Kost

2005-04-01

This paper presents a study of the texture information of high-resolution FLAIR images of the brain with the aim of determining the abnormality and consequently the candidacy of the hippocampus for temporal lobe epilepsy (TLE) surgery. Intensity and volume features of the hippocampus from FLAIR images of the brain have been previously shown to be useful in detecting the abnormal hippocampus in TLE. However, the small size of the hippocampus may limit the texture information. High-resolution FLAIR images show more details of the abnormal intensity variations of the hippocampi and therefore are more suitable for texture analysis. We study and compare the low and high-resolution FLAIR images of six epileptic patients. The hippocampi are segmented manually by an expert from T1-weighted MR images. Then the segmented regions are mapped on the corresponding FLAIR images for texture analysis. The 2-D wavelet transforms of the hippocampi are employed for feature extraction. We compare the ability of the texture features from regular and high-resolution FLAIR images to distinguish normal and abnormal hippocampi. Intracranial EEG results as well as surgery outcome are used as gold standard. The results show that the intensity variations of the hippocampus are related to the abnormalities in the TLE.

Statistical Validation of Automatic Methods for Hippocampus Segmentation in MR Images of Epileptic Patients

PubMed Central

Hosseini, Mohammad-Parsa; Nazem-Zadeh, Mohammad R.; Pompili, Dario; Soltanian-Zadeh, Hamid

2015-01-01

Hippocampus segmentation is a key step in the evaluation of mesial Temporal Lobe Epilepsy (mTLE) by MR images. Several automated segmentation methods have been introduced for medical image segmentation. Because of multiple edges, missing boundaries, and shape changing along its longitudinal axis, manual outlining still remains the benchmark for hippocampus segmentation, which however, is impractical for large datasets due to time constraints. In this study, four automatic methods, namely FreeSurfer, Hammer, Automatic Brain Structure Segmentation (ABSS), and LocalInfo segmentation, are evaluated to find the most accurate and applicable method that resembles the bench-mark of hippocampus. Results from these four methods are compared against those obtained using manual segmentation for T1-weighted images of 157 symptomatic mTLE patients. For performance evaluation of automatic segmentation, Dice coefficient, Hausdorff distance, Precision, and Root Mean Square (RMS) distance are extracted and compared. Among these four automated methods, ABSS generates the most accurate results and the reproducibility is more similar to expert manual outlining by statistical validation. By considering p-value<0.05, the results of performance measurement for ABSS reveal that, Dice is 4%, 13%, and 17% higher, Hausdorff is 23%, 87%, and 70% lower, precision is 5%, -5%, and 12% higher, and RMS is 19%, 62%, and 65% lower compared to LocalInfo, FreeSurfer, and Hammer, respectively. PMID:25571043

A Stereological Study of Synapse Number in the Epileptic Human Hippocampus

PubMed Central

Alonso-Nanclares, Lidia; Kastanauskaite, Asta; Rodriguez, Jose-Rodrigo; Gonzalez-Soriano, Juncal; DeFelipe, Javier

2011-01-01

Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity. PMID:21390290

Interictal scalp electroencephalography and intraoperative electrocorticography in magnetic resonance imaging-negative temporal lobe epilepsy surgery.

PubMed

Burkholder, David B; Sulc, Vlastimil; Hoffman, E Matthew; Cascino, Gregory D; Britton, Jeffrey W; So, Elson L; Marsh, W Richard; Meyer, Fredric B; Van Gompel, Jamie J; Giannini, Caterina; Wass, C Thomas; Watson, Robert E; Worrell, Gregory A

2014-06-01

Scalp electroencephalography (EEG) and intraoperative electrocorticography (ECoG) are routinely used in the evaluation of magnetic resonance imaging-negative temporal lobe epilepsy (TLE) undergoing standard anterior temporal lobectomy with amygdalohippocampectomy (ATL), but the utility of interictal epileptiform discharge (IED) identification and its role in outcome are poorly defined. To determine whether the following are associated with surgical outcomes in patients with magnetic resonance imaging-negative TLE who underwent standard ATL: (1) unilateral-only IEDs on preoperative scalp EEG; (2) complete resection of tissue generating IEDs on ECoG; (3) complete resection of opioid-induced IEDs recorded on ECoG; and (4) location of IEDs recorded on ECoG. Data were gathered through retrospective medical record review at a tertiary referral center. Adult and pediatric patients with TLE who underwent standard ATL between January 1, 1990, and October 15, 2010, were considered for inclusion. Inclusion criteria were magnetic resonance imaging-negative TLE, standard ECoG performed at the time of surgery, and a minimum follow-up of 12 months. Univariate analysis was performed using log-rank time-to-event analysis. Variables reaching significance with log-rank testing were further analyzed using Cox proportional hazards. Excellent or nonexcellent outcome at time of last follow-up. An excellent outcome was defined as Engel class I and a nonexcellent outcome as Engel classes II through IV. Eighty-seven patients met inclusion criteria, with 48 (55%) achieving an excellent outcome following ATL. Unilateral IEDs on scalp EEG (P = .001) and complete resection of brain regions generating IEDs on baseline intraoperative ECoG (P = .02) were associated with excellent outcomes in univariate analysis. Both were associated with excellent outcomes when analyzed with Cox proportional hazards (unilateral-only IEDs, relative risk = 0.31 [95% CI, 0.16-0.64]; complete resection of IEDs on baseline ECoG, relative risk = 0.39 [95% CI, 0.20-0.76]). Overall, 25 of 35 patients (71%) with both unilateral-only IEDs and complete resection of baseline ECoG IEDs had an excellent outcome. Unilateral-only IEDs on preoperative scalp EEG and complete resection of IEDs on baseline ECoG are associated with better outcomes following standard ATL in magnetic resonance imaging-negative TLE. Prospective evaluation is needed to clarify the use of ECoG in tailoring temporal lobectomy.

Multiphoton fluorescence imaging of NADH to quantify metabolic changes in epileptic tissue in vitro

NASA Astrophysics Data System (ADS)

Chia, Thomas H.; Zinter, Joseph; Spencer, Dennis D.; Williamson, Anne; Levene, Michael J.

2007-02-01

A powerful advantage of multiphoton microscopy is its ability to image endogenous fluorophores such as the ubiquitous coenzyme NADH in discrete cellular populations. NADH is integral in both oxidative and non-oxidative cellular metabolism. NADH loses fluorescence upon oxidation to NAD +; thus changes in NADH fluorescence can be used to monitor metabolism. Recent studies have suggested that hypo metabolic astrocytes play an important role in cases of temporal lobe epilepsy (TLE). Current theories suggest this may be due to defective and/or a reduced number of mitochondria or dysfunction of the neuronal-astrocytic metabolic coupling. Measuring NADH fluorescence changes following chemical stimulation enables the quantification of the cellular distribution of metabolic anomalies in epileptic brain tissue compared to healthy tissue. We present what we believe to be the first multiphoton microscopy images of NADH from the human brain. We also present images of NADH fluorescence from the hippocampus of the kainate-treated rat TLE model. In some experiments, human and rat astrocytes were selectively labeled with the fluorescent dye sulforhodamine 101 (SR101). Our results demonstrate that multiphoton microscopy is a powerful tool for assaying the metabolic pathologies associated with temporal lobe epilepsy in humans and in rodent models.

Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy.

PubMed

Kang, Joon Y; Wu, Chengyuan; Tracy, Joseph; Lorenzo, Matthew; Evans, James; Nei, Maromi; Skidmore, Christopher; Mintzer, Scott; Sharan, Ashwini D; Sperling, Michael R

2016-02-01

To describe mesial temporal lobe ablated volumes, verbal memory, and surgical outcomes in patients with medically intractable mesial temporal lobe epilepsy (mTLE) treated with magnetic resonance imaging (MRI)-guided stereotactic laser interstitial thermal therapy (LiTT). We prospectively tracked seizure outcome in 20 patients at Thomas Jefferson University Hospital with drug-resistant mTLE who underwent MRI-guided LiTT from December 2011 to December 2014. Surgical outcome was assessed at 6 months, 1 year, 2 years, and at the most recent visit. Volume-based analysis of ablated mesial temporal structures was conducted in 17 patients with mesial temporal sclerosis (MTS) and results were compared between the seizure-free and not seizure-free groups. Following LiTT, proportions of patients who were free of seizures impairing consciousness (including those with auras only) are as follows: 8 of 15 patients (53%, 95% confidence interval [CI] 30.1-75.2%) after 6 months, 4 of 11 patients (36.4%, 95% CI 14.9-64.8%) after 1 year, 3 of 5 patients (60%, 95% CI 22.9-88.4%) at 2-year follow-up. Median follow-up was 13.4 months after LiTT (range 1.3 months to 3.2 years). Seizure outcome after LiTT suggests an all or none response. Four patients had anterior temporal lobectomy (ATL) after LiTT; three are seizure-free. There were no differences in total ablated volume of the amygdalohippocampus complex or individual volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus between seizure-free and non-seizure-free patients. Contextual verbal memory performance was preserved after LiTT, although decline in noncontextual memory task scores were noted. We conclude that MRI-guided stereotactic LiTT is a safe alternative to ATL in patients with medically intractable mTLE. Individualized assessment is warranted to determine whether the reduced odds of seizure freedom are worth the reduction in risk, discomfort, and recovery time. Larger prospective studies are needed to confirm our preliminary findings, and to define optimal ablation volume and ideal structures for ablation. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

PubMed

Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

2016-09-01

Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the contralateral hippocampus after surgery suggests the possibility of an early post-operative imaging marker to predict surgical outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Study on the Relationships between Intrinsic Functional Connectivity of the Default Mode Network and Transient Epileptic Activity.

PubMed

Lopes, Renaud; Moeller, Friederike; Besson, Pierre; Ogez, François; Szurhaj, William; Leclerc, Xavier; Siniatchkin, Michael; Chipaux, Mathilde; Derambure, Philippe; Tyvaert, Louise

2014-01-01

Simultaneous recording of electroencephalogram and functional MRI (EEG-fMRI) is a powerful tool for localizing epileptic networks via the detection of hemodynamic changes correlated with interictal epileptic discharges (IEDs). fMRI can be used to study the long-lasting effect of epileptic activity by assessing stationary functional connectivity during the resting-state period [especially, the connectivity of the default mode network (DMN)]. Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) are associated with low responsiveness and disruption of DMN activity. A dynamic functional connectivity approach might enable us to determine the effect of IEDs on DMN connectivity and to better understand the correlation between DMN connectivity changes and altered consciousness. We studied dynamic changes in DMN intrinsic connectivity and their relation to IEDs. Six IGE patients (with generalized spike and slow-waves) and 6 TLE patients (with unilateral left temporal spikes) were included. Functional connectivity before, during, and after IEDs was estimated using a sliding window approach and compared with the baseline period. No dependence on window size was observed. The baseline DMN connectivity was decreased in the left hemisphere (ipsilateral to the epileptic focus) in TLEs and was less strong but remained bilateral in IGEs. We observed an overall increase in DMN intrinsic connectivity prior to the onset of IEDs in both IGEs and TLEs. After IEDs in TLEs, we found that DMN connectivity increased before it returned to baseline values. Most of the DMN regions with increased connectivity before and after IEDs were lateralized to the left hemisphere in TLE (i.e., ipsilateral to the epileptic focus). RESULTS suggest that DMN connectivity may facilitate IED generation and may be affected at the time of the IED. However, these results need to be confirmed in a larger independent cohort.

Associative episodic memory and recollective processes in childhood temporal lobe epilepsy.

PubMed

Martins, Sylvie; Guillery-Girard, Bérengère; Clochon, Patrice; Bulteau, Christine; Hertz-Pannier, Lucie; Chiron, Catherine; Eustache, Francis; Jambaqué, Isabelle

2015-03-01

While the current literature on children suffering from temporal lobe epilepsy (CTLE) mostly focuses on material-related episodic memory deficits according to seizure-onset lateralization, the present study examined associative episodic memory according to the type of information to memorize (e.g., factual, spatial, and sequential) and further investigated subjective and objective recollection. Eleven children with left temporal lobe epilepsy (LTLE), 10 children with right temporal lobe epilepsy (RTLE), among whom 9 displayed hippocampal sclerosis (HS), and 42 healthy controls completed the WHAT-WHEN-WHERE protocol (Guillery-Girard et al., 2013). Group comparisons were first conducted according to the affected side and second according to the underlying pathology. Results showed associative memory impairments in patients irrespective of the affected side. Moreover, this study revealed that HS is particularly deleterious to associative and subjective recollection in CTLE. In addition, this study emphasizes the need for assessing episodic memory in childhood TLE beyond material specificity. Copyright © 2015 Elsevier Inc. All rights reserved.

Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

PubMed Central

Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

2014-01-01

Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal brain-derived NSPCs possess some therapeutic effect for TLE treatments although further studies to both increase the yield of NSPC grafts-derived functionally integrated GABAergic neurons and improve cognitive deficits are still needed. PMID:25105891

Physical activity, stigma, and quality of life in patients with epilepsy.

PubMed

Tedrus, Gloria Maria Almeida Souza; Sterca, Guilherme Sabbag; Pereira, Renato Buarque

2017-12-01

Indication of physical activity (PA) for people with epilepsy (PWE) is debatable. This study investigated whether the International Physical Activity Questionnaire (IPAQ) score is related to the clinical aspects of epilepsy, QOLIE-31, and the Stigma Scale of Epilepsy (SSE) score of 67 PWE at a significance level of 5% (p<0.05). About one-third (32.8%) of the PWE were sedentary/irregularly active. Lower QOLIE-31 scores and higher SSE scores were found in PWE who did not practice PA for fear of seizures and in sedentary/irregularly active PWE. Twenty-three percent of the PWE stopped practicing PA for fear of seizures. The predictive factors in the logistic regression equation for not practicing physical activity for fear of seizures were the presence of depressive disorder (p=0.049) and temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) (p=0.024). Most PWE are sedentary and do not practice PA for fear of seizures. Physical activity is negatively influenced by clinical aspects of epilepsy. Less PA is associated with depressive disorder, worse quality of life, and higher perception of stigma. Copyright © 2017 Elsevier Inc. All rights reserved.

Psychotic illness in patients with epilepsy

PubMed Central

Tadokoro, Yukari; Oshima, Tomohiro

2012-01-01

Apart from the rather rare ictal psychotic events, such as non-convulsive status epilepticus, modern epileptic psychoses have been categorized into three main types; chronic and acute interictal psychoses (IIPs) and postictal psychosis (PIP). Together, they comprise 95% of psychoses in patients with epilepsy (PWE). Four major questions, that is, “Is psychosis in PWE a direct consequence of epilepsy or schizophrenia induced by epilepsy?”, “Is psychosis in PWE homogeneous or heterogeneous?”, “Does psychosis in PWE have symptomatological differences from schizophrenia and related disorders?”, “Is psychosis in PWE uniquely associated with temporal lobe epilepsy (TLE)?” are tried to be answered in this review with relevant case presentations. In the final section, we propose a tentative classification of psychotic illness in PWE, with special attention to those who have undergone epilepsy surgery. Psychotic disorders in PWE are often overlooked, mistreated, and consequently lingering on needlessly. While early diagnosis is unanimously supported as a first step to avoid this delay, necessity of switching from antiepileptic drugs with supposedly adverse psychotopic effects. to others is more controversial. To elucidate the riddle of alternative psychosis, we need badly further reliable data. PMID:23139703

Spatial memory for asymmetrical dot locations predicts lateralization among patients with presurgical mesial temporal lobe epilepsy.

PubMed

Brown, Franklin C; Hirsch, Lawrence J; Spencer, Dennis D

2015-11-01

This study examined the ability of an asymmetrical dot location memory test (Brown Location Test, BLT) and two verbal memory tests (Verbal Selective Reminding Test (VSRT) and California Verbal Learning Test, Second Edition (CVLT-II)) to correctly lateralize left (LTLE) or right (RTLE) mesial temporal lobe epilepsy that was confirmed with video-EEG. Subjects consisted of 16 patients with medically refractory RTLE and 13 patients with medically refractory LTLE who were left hemisphere language dominant. Positive predictive values for lateralizing TLE correctly were 87.5% for the BLT, 72.7% for the VSRT, and 80% for the CVLT-II. Binary logistic regression indicated that the BLT alone correctly classified 76.9% of patients with left temporal lobe epilepsy and 87.5% of patients with right temporal lobe epilepsy. Inclusion of the verbal memory tests improved this to 92.3% of patients with left temporal lobe epilepsy and 100% correct classification of patients with right temporal lobe epilepsy. Though of a limited sample size, this study suggests that the BLT alone provides strong laterality information which improves with the addition of verbal memory tests. Copyright © 2015 Elsevier Inc. All rights reserved.

Electroencephalography in Mesial Temporal Lobe Epilepsy: A Review

PubMed Central

Javidan, Manouchehr

2012-01-01

Electroencephalography (EEG) has an important role in the diagnosis and classification of epilepsy. It can provide information for predicting the response to antiseizure drugs and to identify the surgically remediable epilepsies. In temporal lobe epilepsy (TLE) seizures could originate in the medial or lateral neocortical temporal region, and many of these patients are refractory to medical treatment. However, majority of patients have had excellent results after surgery and this often relies on the EEG and magnetic resonance imaging (MRI) data in presurgical evaluation. If the scalp EEG data is insufficient or discordant, invasive EEG recording with placement of intracranial electrodes could identify the seizure focus prior to surgery. This paper highlights the general information regarding the use of EEG in epilepsy, EEG patterns resembling epileptiform discharges, and the interictal, ictal and postictal findings in mesial temporal lobe epilepsy using scalp and intracranial recordings prior to surgery. The utility of the automated seizure detection and computerized mathematical models for increasing yield of non-invasive localization is discussed. This paper also describes the sensitivity, specificity, and predictive value of EEG for seizure recurrence after withdrawal of medications following seizure freedom with medical and surgical therapy. PMID:22957235

Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy.

PubMed

Campo, Pablo; Garrido, Marta I; Moran, Rosalyn J; García-Morales, Irene; Poch, Claudia; Toledano, Rafael; Gil-Nagel, Antonio; Dolan, Raymond J; Friston, Karl J

2013-05-15

Mesial temporal lobe epilepsy (mTLE) is the most prevalent form of focal epilepsy, and hippocampal sclerosis (HS) is considered the most frequent associated pathological finding. Recent connectivity studies have shown that abnormalities, either structural or functional, are not confined to the affected hippocampus, but can be found in other connected structures within the same hemisphere, or even in the contralesional hemisphere. Despite the role of hippocampus in memory functions, most of these studies have explored network properties at resting state, and in some cases compared connectivity values with neuropsychological memory scores. Here, we measured magnetoencephalographic responses during verbal working memory (WM) encoding in left mTLE patients and controls, and compared their effective connectivity within a frontotemporal network using dynamic causal modelling. Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal cortex (IFC), and the medial temporal lobe (MTL). Test for differences in effective connectivity revealed that patients exhibited decreased ipsilesional MTL-ITC backward connectivity, and increased bidirectional IFC-MTL connectivity in the contralesional hemisphere. Critically, a negative correlation was observed between these changes in patients, with decreases in ipsilesional coupling among temporal sources associated with increases contralesional frontotemporal interactions. Furthermore, contralesional frontotemporal interactions were inversely related to task performance and level of education. The results demonstrate that unilateral sclerosis induced local and remote changes in the dynamic organization of a distributed network supporting verbal WM. Crucially, pre-(peri) morbid factors (educational level) were reflected in both cognitive performance and (putative) compensatory changes in physiological coupling. Copyright © 2013 Elsevier Inc. All rights reserved.

The influence of seizure frequency on anterograde and remote memory in mesial temporal lobe epilepsy.

PubMed

Voltzenlogel, Virginie; Vignal, Jean-Pierre; Hirsch, Edouard; Manning, Liliann

2014-10-01

Seizure frequency, although considered as an important factor in memory impairment in mesial temporal epilepsy (mTLE), is mostly confounded with other clinical variables, making it unclear to what extent recurrent seizures actually interfere with memory. The present study focuses on the influence of seizure frequency, studied as a main variable, on anterograde and remote memory. Seventy-one patients with unilateral mTLE were divided into two subgroups, as a function of their seizure frequency (monthly versus weekly seizures). Other seizure-related variables were controlled, namely, lateralisation and type of lesion, age at onset, years of ongoing seizures, etiologic factors, and number of AED. A comprehensive neuropsychological examination, including anterograde memory (verbal and non verbal recognition memory and free recall) tasks together with a large range of tests exploring different domains of remote memory, was carried out. Despite similar results on IQ, executive functions and attention, the low seizure-frequency group performed significantly better than the high seizure-frequency group on anterograde memory tests. Loss of autobiographical episodes and public-events memory, concomitant with spared personal semantic knowledge, was observed in both patient groups compared with healthy subjects. A worsening effect of high seizure frequency was recorded for autobiographical incidents and news-events memory, but unexpectedly, not for memory for famous people. The study of seizure frequency as the main variable leads us to suggest that high seizure frequency, itself, potentiates the effects of mesial temporal lobe damage on episodic memory deficits. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Accelerated long-term forgetting in temporal lobe epilepsy: evidence of improvement after left temporal pole lobectomy.

PubMed

Gallassi, Roberto; Sambati, Luisa; Poda, Roberto; Stanzani Maserati, Michelangelo; Oppi, Federico; Giulioni, Marco; Tinuper, Paolo

2011-12-01

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls. Copyright © 2011 Elsevier Inc. All rights reserved.

Insights into Intrinsic Brain Networks based on Graph Theory and PET in right- compared to left-sided Temporal Lobe Epilepsy.

PubMed

Vanicek, Thomas; Hahn, Andreas; Traub-Weidinger, Tatjana; Hilger, Eva; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert; Pataraia, Ekaterina; Asenbaum-Nan, Susanne

2016-06-28

The human brain exhibits marked hemispheric differences, though it is not fully understood to what extent lateralization of the epileptic focus is relevant. Preoperative [(18)F]FDG-PET depicts lateralization of seizure focus in patients with temporal lobe epilepsy and reveals dysfunctional metabolic brain connectivity. The aim of the present study was to compare metabolic connectivity, inferred from inter-regional [(18)F]FDG PET uptake correlations, in right-sided (RTLE; n = 30) and left-sided TLE (LTLE; n = 32) with healthy controls (HC; n = 31) using graph theory based network analysis. Comparing LTLE and RTLE and patient groups separately to HC, we observed higher lobar connectivity weights in RTLE compared to LTLE for connections of the temporal and the parietal lobe of the contralateral hemisphere (CH). Moreover, especially in RTLE compared to LTLE higher local efficiency were found in the temporal cortices and other brain regions of the CH. The results of this investigation implicate altered metabolic networks in patients with TLE specific to the lateralization of seizure focus, and describe compensatory mechanisms especially in the CH of patients with RTLE. We propose that graph theoretical analysis of metabolic connectivity using [(18)F]FDG-PET offers an important additional modality to explore brain networks.

Regional thalamic neuropathology in patients with hippocampal sclerosis and epilepsy: A postmortem study

PubMed Central

Sinjab, Barah; Martinian, Lillian; Sisodiya, Sanjay M; Thom, Maria

2013-01-01

Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy (TLE), particularly in association with hippocampal sclerosis (HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem (PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25–87 years) and eight controls (age range 38–85 years) were studied. HS was classified as unilateral (UHS, 11 cases), bilateral (BHS, 4 cases) or absent (No-HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet (CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities (NDs) or field fraction staining values (GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus (AV), lateral dorsal nucleus (LD), mediodorsal nucleus (MD), and ventrolateral nucleus (VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No-HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in HS. Significance Our study demonstrates that stereotypical pathologic changes, as seen in HS, are not clearly defined in the thalamus. This may be partly explained by the heterogeneity of our PM study group. With quantitation, there is some evidence for preferential involvement of the MD, suggesting a potential role in TLE, which requires further investigation. PMID:24138281

Interictal Scalp Electroencephalography and Intraoperative Electrocorticography in Magnetic Resonance Imaging–Negative Temporal Lobe Epilepsy Surgery

PubMed Central

Burkholder, David B.; Sulc, Vlastimil; Hoffman, E. Matthew; Cascino, Gregory D.; Britton, Jeffrey W.; So, Elson L.; Marsh, W. Richard; Meyer, Fredric B.; Van Gompel, Jamie J.; Giannini, Caterina; Wass, C. Thomas; Watson, Robert E.; Worrell, Gregory A.

2014-01-01

IMPORTANCE Scalp electroencephalography (EEG) and intraoperative electrocorticography (ECoG) are routinely used in the evaluation of magnetic resonance imaging–negative temporal lobe epilepsy (TLE) undergoing standard anterior temporal lobectomy with amygdalohippocampectomy (ATL), but the utility of interictal epileptiform discharge (IED) identification and its role in outcome are poorly defined. OBJECTIVES To determine whether the following are associated with surgical outcomes in patients with magnetic resonance imaging–negative TLE who underwent standard ATL: (1) unilateral-only IEDs on preoperative scalp EEG; (2) complete resection of tissue generating IEDs on ECoG; (3) complete resection of opioid-induced IEDs recorded on ECoG; and (4) location of IEDs recorded on ECoG. DESIGN, SETTING, AND PARTICIPANTS Data were gathered through retrospective medical record review at a tertiary referral center. Adult and pediatric patients with TLE who underwent standard ATL between January 1, 1990, and October 15, 2010, were considered for inclusion. Inclusion criteria were magnetic resonance imaging–negative TLE, standard ECoG performed at the time of surgery, and a minimum follow-up of 12 months. Univariate analysis was performed using log-rank time-to-event analysis. Variables reaching significance with log-rank testing were further analyzed using Cox proportional hazards. MAIN OUTCOMES AND MEASURES Excellent or nonexcellent outcome at time of last follow-up. An excellent outcome was defined as Engel class I and a nonexcellent outcome as Engel classes II through IV. RESULTS Eighty-seven patients met inclusion criteria, with 48 (55%) achieving an excellent outcome following ATL. Unilateral IEDs on scalp EEG (P = .001) and complete resection of brain regions generating IEDs on baseline intraoperative ECoG (P = .02) were associated with excellent outcomes in univariate analysis. Both were associated with excellent outcomes when analyzed with Cox proportional hazards (unilateral-only IEDs, relative risk = 0.31 [95% CI, 0.16-0.64]; complete resection of IEDs on baseline ECoG, relative risk = 0.39 [95% CI, 0.20-0.76]). Overall, 25 of 35 patients (71%) with both unilateral-only IEDs and complete resection of baseline ECoG IEDs had an excellent outcome. CONCLUSIONS AND RELEVANCE Unilateral-only IEDs on preoperative scalp EEG and complete resection of IEDs on baseline ECoG are associated with better outcomes following standard ATL in magnetic resonance imaging–negative TLE. Prospective evaluation is needed to clarify the use of ECoG in tailoring temporal lobectomy. PMID:24781216

Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR intensity.

PubMed

Nazem-Zadeh, Mohammad-Reza; Schwalb, Jason M; Elisevich, Kost V; Bagher-Ebadian, Hassan; Hamidian, Hajar; Akhondi-Asl, Ali-Reza; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid

2014-07-15

To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for the lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extraoperative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. HVU was estimated to be 3.1×10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating the lateralization results of HVU analysis on these quantities by majority voting has detected the epileptogenic side for 19 out of 20 cases with no wrong lateralization. The presence of MTS in TLE patients is associated with an elevated MD value in the ipsilateral hippocampus and a reduced FA value in the posteroinferior subregion of the ipsilateral cingulum and crus of ipsilateral fornix. When considering all TLE patients, among the mentioned biomarkers the hippocampal MD had the best performance with true detection rate of 90% without any wrong lateralization. The proposed uncertainty based analyses hold promise for improving decision-making for surgical resection. Copyright © 2014 Elsevier B.V. All rights reserved.

Glutamate metabolism in temporal lobe epilepsy as revealed by dynamic proton MRS following the infusion of [U13-C] glucose.

PubMed

Bartnik-Olson, Brenda L; Ding, Daniel; Howe, John; Shah, Amul; Losey, Travis

2017-10-01

Focal metabolic dysfunction commonly observed in temporal lobe epilepsy (TLE), and is associated with the development of medical intractability and neurocognitive deficits. It has not been established if this dysfunction is due to cell loss or biochemical dysfunction in metabolic pathways. To explore this question, dynamic 1 H MRS following an infusion of [U 13 - C] glucose was performed to measure glutamate (Glu) metabolism. Subjects (n=6) showed reduced Glu levels (p<0.01) in the ipsilateral mesial temporal lobe (MTL) compared with controls (n=4). However, the rate of 13 C incorporation into Glu did not differ between those with epilepsy and controls (p=0.77). This suggests that reduced Glu concentrations in the region of the seizure focus are not due to disruptions in metabolic pathways, but may instead be due to neuronal loss or simplification. Copyright © 2017 Elsevier B.V. All rights reserved.

Bringing memory fMRI to the clinic: comparison of seven memory fMRI protocols in temporal lobe epilepsy.

PubMed

Towgood, Karren; Barker, Gareth J; Caceres, Alejandro; Crum, William R; Elwes, Robert D C; Costafreda, Sergi G; Mehta, Mitul A; Morris, Robin G; von Oertzen, Tim J; Richardson, Mark P

2015-04-01

fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation (P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study.

PubMed

Van Paesschen, W; King, M D; Duncan, J S; Connelly, A

2001-07-01

To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe

Human iPSC-Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy

DTIC Science & Technology

2015-10-01

1) Induction of status epilepticus (SE) in young rats through kainic acid injections to generate rats exhibiting chronic TLE typified by SRS. (2...of status epilepticus (SE) via graded kainic acid injections, termination of acute seizures 2 hours after SE onset via diazepam injections and...injections to these rats to induce acute seizures or status epilepticus (SE) in 11 separate experimental sessions (n=8-12/session). These experiments

Automated volumetry for unilateral hippocampal sclerosis detection in patients with temporal lobe epilepsy.

PubMed

Martins, Cristina; Moreira da Silva, Nadia; Silva, Guilherme; Rozanski, Verena E; Silva Cunha, Joao Paulo

2016-08-01

Hippocampal sclerosis (HS) is the most common cause of temporal lobe epilepsy (TLE) and can be identified in magnetic resonance imaging as hippocampal atrophy and subsequent volume loss. Detecting this kind of abnormalities through simple radiological assessment could be difficult, even for experienced radiologists. For that reason, hippocampal volumetry is generally used to support this kind of diagnosis. Manual volumetry is the traditional approach but it is time consuming and requires the physician to be familiar with neuroimaging software tools. In this paper, we propose an automated method, written as a script that uses FSL-FIRST, to perform hippocampal segmentation and compute an index to quantify hippocampi asymmetry (HAI). We compared the automated detection of HS (left or right) based on the HAI with the agreement of two experts in a group of 19 patients and 15 controls, achieving 84.2% sensitivity, 86.7% specificity and a Cohen's kappa coefficient of 0.704. The proposed method is integrated in the "Advanced Brain Imaging Lab" (ABrIL) cloud neurocomputing platform. The automated procedure is 77% (on average) faster to compute vs. the manual volumetry segmentation performed by an experienced physician.

Gender differences in prevalence of psychiatric disorders, levels of alexithymia, and coping strategies in patients with refractory mesial temporal epilepsy and comorbid psychogenic nonepileptic seizures.

PubMed

de Barros, Amanda Cristian Serafim; Furlan, Ana Eliza Romano; Marques, Lucia Helena Neves; de Araújo Filho, Gerardo Maria

2018-05-01

The objective of this study was to investigate the psychological aspects and psychiatric disorders (PDs) in patients dually diagnosed with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) with psychogenic nonepileptic seizures (PNES) treated in a tertiary center in order to find any gender differences in psychiatric, clinical, and sociodemographic characteristics. Psychiatric assessment was performed through the Diagnostic and Statistical Manual for Psychiatric Disorders - 5th edition (DSM-5). The Brazilian versions of the Medical Outcomes Study 36 (SF-36), Toronto Alexithymia Scale (TAS-20), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Ways of Coping Checklist (WCC) were applied. Of the 47 patients enrolled (25 females; 53.2%), females were significantly more likely to have a history of previous psychiatric treatment (P=0.02), family history of epilepsy (P=0.01), and family history of PD (P=0.03). They also presented earlier onset of PNES (P=0.01) and higher PNES duration (P=0.02) compared with males. Major depressive disorder (MDD) was the most frequent PD (24; 51.0%). Females presented more psychiatric diagnoses (P<0.001), more diagnoses of MDD (P<0.001), and posttraumatic stress disorder (PTSD) (P<0.001). Several differences regarding quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies were observed between groups. There are significant gender differences in psychiatric, clinical, and sociodemographic aspects in a group of patients with TLE-MTS and PNES, as well as in quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies. These gender differences suggest that specific approaches might be adopted depending on the patient's gender and, consequently, their distinct psychological/psychiatric profile. Copyright © 2018 Elsevier Inc. All rights reserved.

Neurofibromin Regulates Seizure Attacks in the Rat Pilocarpine-Induced Model of Epilepsy.

PubMed

Ren, Min; Li, Kunyi; Wang, Dan; Guo, Jiamei; Li, Jing; Yang, Guang; Long, Xianghua; Shen, Wenjing; Hu, Rong; Wang, Xuefeng; Zeng, Kebin

2016-11-01

Studies have shown that neurofibromin (NF1) restricts GABA release at inhibitory synapses and regulates dendritic spine formation, which may play an important role in temporal lobe epilepsy (TLE). NF1 expression was detected by double-label immunofluorescence, immunohistochemistry, and western blot analysis in the brains of pilocarpine-induced epilepsy model rats at 6 h, 24 h, 72 h, 7 days, 14 days, 30 days, and 60 days after kindling. NF1 was localized primarily in the nucleus and cytoplasm of neurons. NF1 protein levels significantly increased in the chronic phase (from 7 days until 60 days) in this epileptic rat model. After NF1 expression was knocked down by specific siRNA, the effects of kindling with pilocarpine were evaluated on the 7th day after kindling. The onset latencies of pilocarpine-induced seizures were elevated, and the seizure frequency and duration were reduced in these rats. Our study demonstrates that NF1 promoted seizure attacks in rats with pilocarpine-induced epilepsy.

Perspectives on treatment options for mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Palleria, Caterina; Coppola, Antonietta; Citraro, Rita; Del Gaudio, Luigi; Striano, Salvatore; De Sarro, Giovambattista; Russo, Emilio

2015-01-01

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is a syndrome that is often refractory to drug treatment. The effects on specific syndromes are not currently available from the pre-marketing clinical development of new AEDs; this does not allow the prediction of whether new drugs will be more effective in the treatment of some patients. We have reviewed all the existing literature relevant to the understanding of a potential effectiveness in MTLE-HS patients for the latest AEDs, namely brivaracetam, eslicarbazepine, lacosamide, perampanel and retigabine also including the most relevant clinical data and a brief description of their pharmacological profile. Records were identified using predefined search criteria using electronic databases (e.g., PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published up to the 15 June 2015 were included. All the drugs considered have the potential to be effective in the treatment of MTLE-HS; in fact, they possess proven efficacy in animal models; currently considered valuable tools for predicting drug efficacy in TLE. Furthermore, for some of these (e.g., lacosamide and eslicarbazepine) data are already available from post-marketing studies while brivaracetam acting on SV2A like levetiracetam might have the same potential effectiveness with the possibility to be more efficacious considering its ability to inhibit voltage gated sodium channels; finally, perampanel and retigabine are very effective drugs in animal models of TLE.

Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex.

PubMed

Angamo, Eskedar Ayele; ul Haq, Rizwan; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe; Kovács, Richard

2017-08-23

Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K⁺] O ) were recorded in parallel with tissue pO₂ and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO₂ following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K⁺] O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism.

Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex

PubMed Central

Angamo, Eskedar Ayele; Haq, Rizwan ul; Rösner, Jörg; Gabriel, Siegrun; Gerevich, Zoltán; Heinemann, Uwe

2017-01-01

Neuronal lactate uptake supports energy metabolism associated with synaptic signaling and recovery of extracellular ion gradients following neuronal activation. Altered expression of the monocarboxylate transporters (MCT) in temporal lobe epilepsy (TLE) hampers lactate removal into the bloodstream. The resulting increase in parenchymal lactate levels might exert both, anti- and pro-ictogen effects, by causing acidosis and by supplementing energy metabolism, respectively. Hence, we assessed the contribution of lactate to the maintenance of transmembrane potassium gradients, synaptic signaling and pathological network activity in chronic epileptic human tissue. Stimulus induced and spontaneous field potentials and extracellular potassium concentration changes (∆[K+]O) were recorded in parallel with tissue pO2 and pH in slices from TLE patients while blocking MCTs by α-cyano-4-hydroxycinnamic acid (4-CIN) or d-lactate. Intrinsic lactate contributed to the oxidative energy metabolism in chronic epileptic tissue as revealed by the changes in pO2 following blockade of lactate uptake. However, unlike the results in rat hippocampus, ∆[K+]O recovery kinetics and field potential amplitude did not depend on the presence of lactate. Remarkably, inhibition of lactate uptake exerted pH-independent anti-seizure effects both in healthy rat and chronic epileptic tissue and this effect was partly mediated via adenosine 1 receptor activation following decreased oxidative metabolism. PMID:28832554

Consciousness and epilepsy: why are complex-partial seizures complex?

PubMed Central

Englot, Dario J.; Blumenfeld, Hal

2010-01-01

Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral changes depend on seizure spread to subcortical structures including the lateral septum. Understanding the contributions of network inhibition to impaired consciousness in TLE is an important goal, as recurrent limbic seizures often result in cortical dysfunction during and between epileptic events that adversely affects patients’ quality of life. PMID:19818900

Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

PubMed

Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

2017-08-01

Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to anti-epileptic effects of aspirin.

Mesial temporal lobe epilepsy lateralization using SPHARM-based features of hippocampus and SVM

NASA Astrophysics Data System (ADS)

Esmaeilzadeh, Mohammad; Soltanian-Zadeh, Hamid; Jafari-Khouzani, Kourosh

2012-02-01

This paper improves the Lateralization (identification of the epileptogenic hippocampus) accuracy in Mesial Temporal Lobe Epilepsy (mTLE). In patients with this kind of epilepsy, usually one of the brain's hippocampi is the focus of the epileptic seizures, and resection of the seizure focus is the ultimate treatment to control or reduce the seizures. Moreover, the epileptogenic hippocampus is prone to shrinkage and deformation; therefore, shape analysis of the hippocampus is advantageous in the preoperative assessment for the Lateralization. The method utilized for shape analysis is the Spherical Harmonics (SPHARM). In this method, the shape of interest is decomposed using a set of bases functions and the obtained coefficients of expansion are the features describing the shape. To perform shape comparison and analysis, some pre- and post-processing steps such as "alignment of different subjects' hippocampi" and the "reduction of feature-space dimension" are required. To this end, first order ellipsoid is used for alignment. For dimension reduction, we propose to keep only the SPHARM coefficients with maximum conformity to the hippocampus shape. Then, using these coefficients of normal and epileptic subjects along with 3D invariants, specific lateralization indices are proposed. Consequently, the 1536 SPHARM coefficients of each subject are summarized into 3 indices, where for each index the negative (positive) value shows that the left (right) hippocampus is deformed (diseased). Employing these indices, the best achieved lateralization accuracy for clustering and classification algorithms are 85% and 92%, respectively. This is a significant improvement compared to the conventional volumetric method.

Brain lateralization and neural plasticity for musical and cognitive abilities in an epileptic musician

PubMed Central

Trujillo-Pozo, Isabel; Martín-Monzón, Isabel; Rodríguez-Romero, Rafael

2013-01-01

The use of intracarotid propofol procedure (IPP) when assessing musical lateralization has not been reported in literature up to now. This procedure (similar to Wada Test) has provided the opportunity to investigate not only lateralization of language and memory functions on epileptic patients but also offers a functional mapping approach with superior spatial and temporal resolution to analyze the lateralization of musical abilities. Findings in literature suggest that musical training modifies functional and structural brain organization. We studied hemispheric lateralization in a professional musician, a 33 years old woman with refractory left medial temporal lobe (MTL) epilepsy (TLE). A longitudinal neuropsychological study was performed over a period of 21 months. Before epilepsy surgery, musical abilities, language and memory were tested during IPP by means of a novel and exhaustive neuropsychological battery focusing on the processing of music. We used a selection of stimuli to analyze listening, score reading, and tempo discrimination. Our results suggested that IPP is an excellent method to determine not only language, semantic, and episodic memory, but also musical dominance in a professional musician who may be candidate for epilepsy surgery. Neuropsychological testing revealed that right hemisphere's patient is involved in semantic and episodic musical memory processes, whereas her score reading and tempo processing require contribution from both hemispheres. At one-year follow-up, outcome was excellent with respect to seizures and professional skills, meanwhile cognitive abilities improved. These findings indicate that IPP helps to predict who might be at risk for postoperative musical, language, and memory deficits after epilepsy surgery. Our research suggests that musical expertise and epilepsy critically modifies long-term memory processes and induces brain structural and functional plasticity. PMID:24367312

Reducing versus stopping antiepileptic medications after temporal lobe surgery

PubMed Central

Yardi, Ruta; Irwin, Anna; Kayyali, Husam; Gupta, Ajay; Nair, Dileep; Gonzalez-Martinez, Jorge; Bingaman, William; Najm, Imad M; Jehi, Lara E

2014-01-01

Objective To study the safety of antiepileptic drug (AED) withdrawal after temporal lobe epilepsy (TLE) surgery. Methods We reviewed patients who underwent TLE surgery from 1995 to 2011, collecting data on doses, dates of AED initiation, reduction, and discontinuation. Predictors of seizure outcome were defined using Cox-proportional hazard modeling and adjusted for, while comparing longitudinal seizure-freedom in patients for whom AEDs were unchanged after resection as opposed to reduced or stopped. Results A total of 609 patients (86% adults) were analyzed. Follow-up ranged from 0.5 to 16.7 years. Most (64%) had hippocampal sclerosis. Overall, 229 patients had remained on their same baseline AEDs, while 380 patients stopped (127 cases) or reduced (253 cases) their AEDs. Mean timing of the earliest AED change was shorter in patients with recurrent seizures (1.04 years) compared to those seizure-free at last follow-up (1.44 years; P-value 0.03). Whether AEDs were withdrawn 12 or 24 months after surgery, there was a 10–25% higher risk of breakthrough seizures within the subsequent 2 years. However, 70% of patients with seizure recurrence after AED discontinuation reachieved remission, as opposed to 50% of those whose seizures recurred while reducing AEDs (P = 0.0001). Long-term remission rates were similar in both AED discontinuation and “unchanged” groups (82% remission for AEDs withdrawn after 1 year and 90% for AEDs withdrawn after 2 years), while only 65% of patients whose recurrences started during AED reduction achieved a 2-year remission by last follow-up. Interpretation AED withdrawal increases the short-term risk of breakthrough seizures after TLE surgery, and may alter the long-term disease course in some patients. PMID:25356390

The brain connectome as a personalized biomarker of seizure outcomes after temporal lobectomy.

PubMed

Bonilha, Leonardo; Jensen, Jens H; Baker, Nathaniel; Breedlove, Jesse; Nesland, Travis; Lin, Jack J; Drane, Daniel L; Saindane, Amit M; Binder, Jeffrey R; Kuzniecky, Ruben I

2015-05-05

We examined whether individual neuronal architecture obtained from the brain connectome can be used to estimate the surgical success of anterior temporal lobectomy (ATL) in patients with temporal lobe epilepsy (TLE). We retrospectively studied 35 consecutive patients with TLE who underwent ATL. The structural brain connectome was reconstructed from all patients using presurgical diffusion MRI. Network links in patients were standardized as Z scores based on connectomes reconstructed from healthy controls. The topography of abnormalities in linkwise elements of the connectome was assessed on subnetworks linking ipsilateral temporal with extratemporal regions. Predictive models were constructed based on the individual prevalence of linkwise Z scores >2 and based on presurgical clinical data. Patients were more likely to achieve postsurgical seizure freedom if they exhibited fewer abnormalities within a subnetwork composed of the ipsilateral hippocampus, amygdala, thalamus, superior frontal region, lateral temporal gyri, insula, orbitofrontal cortex, cingulate, and lateral occipital gyrus. Seizure-free surgical outcome was predicted by neural architecture alone with 90% specificity (83% accuracy), and by neural architecture combined with clinical data with 94% specificity (88% accuracy). Individual variations in connectome topography, combined with presurgical clinical data, may be used as biomarkers to better estimate surgical outcomes in patients with TLE. © 2015 American Academy of Neurology.

Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy.

PubMed

Lee, Ricky W; Hoogs, Marietta M; Burkholder, David B; Trenerry, Max R; Drazkowski, Joseph F; Shih, Jerry J; Doll, Karey E; Tatum, William O; Cascino, Gregory D; Marsh, W Richard; Wirrell, Elaine C; Worrell, Gregory A; So, Elson L

2014-07-01

We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data. Copyright © 2014 Elsevier B.V. All rights reserved.

Earlier tachycardia onset in right than left mesial temporal lobe seizures.

PubMed

Kato, Kazuhiro; Jin, Kazutaka; Itabashi, Hisashi; Iwasaki, Masaki; Kakisaka, Yosuke; Aoki, Masashi; Nakasato, Nobukazu

2014-10-07

To clarify whether the presence and timing of peri-ictal heart rate (HR) change is a seizure lateralizing sign in patients with mesial temporal lobe epilepsy (mTLE). Long-term video EEGs were retrospectively reviewed in 21 patients, 7 men and 14 women aged 13 to 67 years, diagnosed as mTLE with MRI lesions in the mesial temporal structures (hippocampal sclerosis in 20 cases, amygdala hypertrophy in 1 case). Seventy-seven partial seizures without secondary generalization were extracted. Peri-ictal HR change was compared between 29 right seizures (9 patients) and 48 left seizures (12 patients). HR abruptly increased in all 29 right seizures and 42 of 48 left seizures. Onset time of HR increase in relation to ictal EEG onset was significantly earlier in right seizures than in left seizures (mean ± SD, -11.5 ± 14.8 vs 9.2 ± 21.7 seconds; p < 0.0001). Time of maximum HR was also significantly earlier in right seizures than in left seizures (36.0 ± 18.1 vs 58.0 ± 28.7 seconds; p < 0.0001). Maximum HR changes from baseline showed no significant difference between right and left seizures (47.5 ± 19.1 vs 40.8 ± 20.0/min). Significantly earlier tachycardia in right than left mTLE seizures supports previous hypotheses that the right cerebral hemisphere is dominant in the sympathetic network. No HR change, or delayed tachycardia possibly due to seizure propagation to the right hemisphere, may be a useful lateralizing sign of left mTLE seizures. © 2014 American Academy of Neurology.

Interictal 18FDG PET findings in temporal lobe epilepsy with déjà vu.

PubMed

Adachi, N; Koutroumanidis, M; Elwes, R D; Polkey, C E; Binnie, C D; Reynolds, E H; Barrington, S F; Maisey, M N; Panayiotopoulos, C P

1999-01-01

The authors studied the functional anatomy of the déjà vu (DV) experience in nonlesional temporal lobe epilepsy (TLE), using interictal fluorine-18 fluorodeoxyglucose PET in 14 patients with and 17 patients without DV. Several clinical conditions, such as age at PET study, side of ictal onset zone, and dominance for language, were no different between the two groups. The patients with DV showed significant relative reductions in glucose metabolism in the mesial temporal structures and the parietal cortex. The findings demonstrate that ictal DV is of no lateralizing value. They further suggest that temporal lobe dysfunction is necessary but not sufficient for the generation of DV. Extensive association cortical areas may be involved as part of the network that integrates this distinct experience.

NeuroKinect: A Novel Low-Cost 3Dvideo-EEG System for Epileptic Seizure Motion Quantification

PubMed Central

Cunha, João Paulo Silva; Choupina, Hugo Miguel Pereira; Rocha, Ana Patrícia; Fernandes, José Maria; Achilles, Felix; Loesch, Anna Mira; Vollmar, Christian; Hartl, Elisabeth; Noachtar, Soheyl

2016-01-01

Epilepsy is a common neurological disorder which affects 0.5–1% of the world population. Its diagnosis relies both on Electroencephalogram (EEG) findings and characteristic seizure−induced body movements − called seizure semiology. Thus, synchronous EEG and (2D)video recording systems (known as Video−EEG) are the most accurate tools for epilepsy diagnosis. Despite the establishment of several quantitative methods for EEG analysis, seizure semiology is still analyzed by visual inspection, based on epileptologists’ subjective interpretation of the movements of interest (MOIs) that occur during recorded seizures. In this contribution, we present NeuroKinect, a low-cost, easy to setup and operate solution for a novel 3Dvideo-EEG system. It is based on a RGB-D sensor (Microsoft Kinect camera) and performs 24/7 monitoring of an Epilepsy Monitoring Unit (EMU) bed. It does not require the attachment of any reflectors or sensors to the patient’s body and has a very low maintenance load. To evaluate its performance and usability, we mounted a state-of-the-art 6-camera motion-capture system and our low-cost solution over the same EMU bed. A comparative study of seizure-simulated MOIs showed an average correlation of the resulting 3D motion trajectories of 84.2%. Then, we used our system on the routine of an EMU and collected 9 different seizures where we could perform 3D kinematic analysis of 42 MOIs arising from the temporal (TLE) (n = 19) and extratemporal (ETE) brain regions (n = 23). The obtained results showed that movement displacement and movement extent discriminated both seizure MOI groups with statistically significant levels (mean = 0.15 m vs. 0.44 m, p<0.001; mean = 0.068 m3 vs. 0.14 m3, p<0.05, respectively). Furthermore, TLE MOIs were significantly shorter than ETE (mean = 23 seconds vs 35 seconds, p<0.01) and presented higher jerking levels (mean = 345 ms−3 vs 172 ms−3, p<0.05). Our newly implemented 3D approach is faster by 87.5% in extracting body motion trajectories when compared to a 2D frame by frame tracking procedure. We conclude that this new approach provides a more comfortable (both for patients and clinical professionals), simpler, faster and lower-cost procedure than previous approaches, therefore providing a reliable tool to quantitatively analyze MOI patterns of epileptic seizures in the routine of EMUs around the world. We hope this study encourages other EMUs to adopt similar approaches so that more quantitative information is used to improve epilepsy diagnosis. PMID:26799795

The right hemisphere's contribution to discourse processing: A study in temporal lobe epilepsy.

PubMed

Lomlomdjian, Carolina; Múnera, Claudia P; Low, Daniel M; Terpiluk, Verónica; Solís, Patricia; Abusamra, Valeria; Kochen, Silvia

2017-08-01

Discourse skills - in which the right hemisphere has an important role - enables verbal communication by selecting contextually relevant information and integrating it coherently to infer the correct meaning. However, language research in epilepsy has focused on single word analysis related mainly to left hemisphere processing. The purpose of this study was to investigate discourse abilities in patients with right lateralized medial temporal lobe epilepsy (RTLE) by comparing their performance to that of patients with left temporal lobe epilepsy (LTLE). 74 pharmacoresistant temporal lobe epilepsy (TLE) patients were evaluated: 34 with RTLE and 40 with LTLE. Subjects underwent a battery of tests that measure comprehension and production of conversational and narrative discourse. Disease related variables and general neuropsychological data were evaluated. The RTLE group presented deficits in interictal conversational and narrative discourse, with a disintegrated speech, lack of categorization and misinterpretation of social meaning. LTLE group, on the other hand, showed a tendency to lower performance in logical-temporal sequencing. RTLE patients showed discourse deficits which have been described in right hemisphere damaged patients due to other etiologies. Medial and anterior temporal lobe structures appear to link semantic, world knowledge, and social cognition associated areas to construct a contextually related coherent meaning. Copyright © 2017 Elsevier Inc. All rights reserved.

Parahippocampal epilepsy with subtle dysplasia: A cause of "imaging negative" partial epilepsy.

PubMed

Pillay, Neelan; Fabinyi, Gavin C A; Myles, Terry S; Fitt, Gregory J; Berkovic, Samuel F; Jackson, Graeme D

2009-12-01

Lesion-negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging-negative frontal or temporal lobe epilepsy. We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T(1)- and T(2)-weighted images with relative preservation of the gray-white matter boundary on T(1)-weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure-free (one has occasional auras only, follow-up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. In patients with lesion-negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.

Characterization of focal cortical dysplasia with balloon cells by layer-specific markers: Evidence for differential vulnerability of interneurons.

PubMed

Nakagawa, Julia M; Donkels, Catharina; Fauser, Susanne; Schulze-Bonhage, Andreas; Prinz, Marco; Zentner, Josef; Haas, Carola A

2017-04-01

Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer-specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region. We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer-specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32-positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin- and Calretinin-positive interneurons in layers II and III were not different from controls, whereas Parvalbumin-expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4-positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b. The application of a broad panel of markers defining layer-specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin-positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Frontal lobe epileptic seizures are accompanied by elevated pitch during verbal communication.

PubMed

Speck, Iva; Echternach, Matthias; Sammler, Daniela; Schulze-Bonhage, Andreas

2018-03-01

The objective of our study was to assess alterations in speech as a possible localizing sign in frontal lobe epilepsy. Ictal speech was analyzed in 18 patients with frontal lobe epilepsy (FLE) during seizures and in the interictal period. Matched identical words were analyzed regarding alterations in fundamental frequency (ƒo) as an approximation of pitch. In patients with FLE, ƒo of ictal utterances was significantly higher than ƒo in interictal recordings (p = 0.016). Ictal ƒo increases occurred in both FLE of right and left seizure origin. In contrast, a matched temporal lobe epilepsy (TLE) group showed less pronounced increases in ƒo, and only in patients with right-sided seizure foci. This study for the first time shows significant voice alterations in ictal speech in a cohort of patients with FLE. This may contribute to the localization of the epileptic focus. Increases in ƒo were interestingly found in frontal lobe seizures with origin in either hemisphere, suggesting a bilateral involvement to the planning of speech production, in contrast to a more right-sided lateralization of pitch perception in prosodic processing. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Abnormal UP/DOWN Membrane Potential Dynamics Coupled with the Neocortical Slow Oscillation in Dentate Granule Cells during the Latent Phase of Temporal Lobe Epilepsy.

PubMed

Ouedraogo, David W; Lenck-Santini, Pierre-Pascal; Marti, Geoffrey; Robbe, David; Crépel, Valérie; Epsztein, Jérôme

2016-01-01

The dentate gyrus, a major entry point to the hippocampus, gates (or filters) incoming information from the cortex. During sleep or anesthesia, the slow-wave oscillation (SWO) orchestrates hippocampus-neocortex communication, which is important for memory formation. The dentate gate is altered in temporal lobe epilepsy (TLE) early during epileptogenesis, which favors the propagation of pathological activities. Yet, whether the gating of physiological SWO by dentate granule cells (DGCs) is altered in TLE has remained unexplored. We combined intracellular recordings of membrane potential (V m) of DGCs and local field potential recordings of the SWO in parietal cortex in anesthetized rats early during epileptogenesis [post-status epilepticus (SE) rats]. As expected, in control rats, the V m of DGCs weakly and rarely oscillated in the SWO frequency range. In contrast, in post-SE rats, the V m of DGCs displayed strong and long-lasting SWO. In these cells, clear UP and DOWN states, in phase with the neocortical SWO, led to a bimodal V m distribution. In post-SE rats, the firing of DGCs was increased and more temporally modulated by the neocortical SWO. We conclude that UP/DOWN state dynamics dominate the V m of DGCs and firing early during epileptogenesis. This abnormally strong neocortical influence on the dynamics of DGCs may profoundly modify the hippocampus-neocortex dialogue during sleep and associated cognitive functions.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients.

PubMed

Doucet, Gaelle E; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients

PubMed Central

Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates. PMID:26594628

Serotonin 1A receptors, depression, and memory in temporal lobe epilepsy.

PubMed

Theodore, William H; Wiggs, Edythe A; Martinez, Ashley R; Dustin, Irene H; Khan, Omar I; Appel, Shmuel; Reeves-Tyer, Pat; Sato, Susumu

2012-01-01

Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous positron emission tomography (PET) studies have shown reduced mesial temporal 5HT1A-receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A-receptor binding measured with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18FCWAY) PET in a cross-sectional study. We studied 40 patients (24 male; mean age 34.5 ± 10.7 years) with TLE. Seizure diagnosis and focus localization were based on ictal video-electroencephalography (EEG) recording. Patients had neuropsychological testing with Wechsler Adult Intelligence Score III (WAIS III) and Wechsler Memory Score III (WMS III) on stable antiepileptic drug (AED) regimens at least 24 h since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with 18FCWAY, a fluorinated derivative of WAY 100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected 18FCWAY volume of distribution (V/f1). Hippocampal V/f1 was significantly lower in area ipsilateral than contralateral to the epileptic focus (73.7 ± 27.3 vs. 95.4 ± 28.4; p < 0.001). We found a significant relation between both left hippocampal 18FCWAY V/f1 (r = 0.41; p < 0.02) and left hippocampal volume (r = 0.36; p < 0.03) and delayed auditory memory score. On multiple regression, there was a significant effect of the interaction of left hippocampal 18FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal 18FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 ± 7.0. There was a significant inverse relation between BDI and 18FCWAY V/f1 ipsilateral to the patient's epileptic focus (r = 0.38 p < 0.02). There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory. Our study suggests that reduced left hippocampal 5HT1A-receptor binding may play a role in memory impairment in patients with TLE. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

From "rest" to language task: Task activation selects and prunes from broader resting-state network.

PubMed

Doucet, Gaelle E; He, Xiaosong; Sperling, Michael R; Sharan, Ashwini; Tracy, Joseph I

2017-05-01

Resting-state networks (RSNs) show spatial patterns generally consistent with networks revealed during cognitive tasks. However, the exact degree of overlap between these networks has not been clearly quantified. Such an investigation shows promise for decoding altered functional connectivity (FC) related to abnormal language functioning in clinical populations such as temporal lobe epilepsy (TLE). In this context, we investigated the network configurations during a language task and during resting state using FC. Twenty-four healthy controls, 24 right and 24 left TLE patients completed a verb generation (VG) task and a resting-state fMRI scan. We compared the language network revealed by the VG task with three FC-based networks (seeding the left inferior frontal cortex (IFC)/Broca): two from the task (ON, OFF blocks) and one from the resting state. We found that, for both left TLE patients and controls, the RSN recruited regions bilaterally, whereas both VG-on and VG-off conditions produced more left-lateralized FC networks, matching more closely with the activated language network. TLE brings with it variability in both task-dependent and task-independent networks, reflective of atypical language organization. Overall, our findings suggest that our RSN captured bilateral activity, reflecting a set of prepotent language regions. We propose that this relationship can be best understood by the notion of pruning or winnowing down of the larger language-ready RSN to carry out specific task demands. Our data suggest that multiple types of network analyses may be needed to decode the association between language deficits and the underlying functional mechanisms altered by disease. Hum Brain Mapp 38:2540-2552, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy.

PubMed

Coan, Ana C; Chaudhary, Umair J; Frédéric Grouiller; Campos, Brunno M; Perani, Suejen; De Ciantis, Alessio; Vulliemoz, Serge; Diehl, Beate; Beltramini, Guilherme C; Carmichael, David W; Thornton, Rachel C; Covolan, Roberto J; Cendes, Fernando; Lemieux, Louis

2016-06-01

Drug-resistant temporal lobe epilepsy (TLE) often requires thorough investigation to define the epileptogenic zone for surgical treatment. We used simultaneous interictal scalp EEG-fMRI to evaluate its value for predicting long-term postsurgical outcome. 30 patients undergoing presurgical evaluation and proceeding to temporal lobe (TL) resection were studied. Interictal epileptiform discharges (IEDs) were identified on intra-MRI EEG and used to build a model of haemodynamic changes. In addition, topographic electroencephalographic correlation maps were calculated between the average IED during video-EEG and intra-MRI EEG, and used as a condition. This allowed the analysis of all data irrespective of the presence of IED on intra-MRI EEG. Mean follow-up after surgery was 46 months. International League Against Epilepsy (ILAE) outcomes 1 and 2 were considered good, and 3-6 poor, surgical outcome. Haemodynamic maps were classified according to the presence (Concordant) or absence (Discordant) of Blood Oxygen Level-Dependent (BOLD) change in the TL overlapping with the surgical resection. The proportion of patients with good surgical outcome was significantly higher (13/16; 81%) in the Concordant than in the Discordant group (3/14; 21%) (χ(2) test, Yates correction, p=0.003) and multivariate analysis showed that Concordant BOLD maps were independently related to good surgical outcome (p=0.007). Sensitivity and specificity of EEG-fMRI results to identify patients with good surgical outcome were 81% and 79%, respectively, and positive and negative predictive values were 81% and 79%, respectively. The presence of significant BOLD changes in the area of resection on interictal EEG-fMRI in patients with TLE retrospectively confirmed the epileptogenic zone. Surgical resection including regions of haemodynamic changes in the TL may lead to better postoperative outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Target-Selectivity of Parvalbumin-Positive Interneurons in Layer II of Medial Entorhinal Cortex in Normal and Epileptic Animals

PubMed Central

Armstrong, Caren; Wang, Jessica; Lee, Soo Yeun; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2015-01-01

The medial entorhinal cortex layer II (MEClayerII) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII. However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII. However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII. Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. PMID:26663222

Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.

PubMed

Armstrong, Caren; Wang, Jessica; Yeun Lee, Soo; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2016-06-01

The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance our knowledge about the organization of perisomatic inhibition both in control and in epileptic animals. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration.

PubMed

Auladell, Carme; de Lemos, Luisa; Verdaguer, Ester; Ettcheto, Miren; Busquets, Oriol; Lazarowski, Alberto; Beas-Zarate, Carlos; Olloquequi, Jordi; Folch, Jaume; Camins, Antoni

2017-01-01

Chemoconvulsants that induce status epilepticus in rodents have been widely used over the past decades due to their capacity to reproduce with high similarity neuropathological and electroencephalographic features observed in patients with temporal lobe epilepsy (TLE). Kainic acid  is one of the most used chemoconvulsants in experimental models. KA administration mainly induces neuronal loss in the hippocampus. We focused the present review inthe c-Jun N-terminal kinase-signaling pathway (JNK), since it has been shown to play a key role in the process of neuronal death following KA activation. Among the three isoforms of JNK (JNK1, JNK2, JNK3), JNK3 is widely localized in the majority of areas of the hippocampus, whereas JNK1 levels are located exclusively in the CA3 and CA4 areas and in dentate gyrus. Disruption of the gene encoding JNK3 in mice renders neuroprotection to KA, since these animals showed a reduction in seizure activity and a diminution in hippocampal neuronal apoptosis. In light of this, JNK3 could be a promising subcellular target for future therapeutic interventions in epilepsy.

Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

PubMed

Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

2008-01-01

Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy.

PubMed

Post, Julia M; Loch, Sebastian; Lerner, Raissa; Remmers, Floortje; Lomazzo, Ermelinda; Lutz, Beat; Bindila, Laura

2018-01-01

Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2) was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ), maximal electroshock (MES) and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA). KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE) depending on the route of KA administration; intracerebral (i.c.) injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p.) injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i) neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii) temporal dynamics of eCB and eicosanoid (eiC) levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH) in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.

Down-regulation of Transducin-Like Enhancer of Split protein 4 in hepatocellular carcinoma promotes cell proliferation and epithelial-Mesenchymal-Transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Xiao-cai; Xiao, Cui-cui; Li, Hua

Background: Transducin-Like Enhancer of Split protein 4 (TLE4) has been reported to be involved in some subsets of acute myeloid leukemia and colorectal cancer. In the present study, we aimed to explore the role of TLE4 in tumorigenesis and cancer progression in hepatocellular carcinoma (HCC). Methods: The expression pattern of TLE4 in HCC was determined by Western-blot and qRT-PCR, gain-of-function and loss-of-function was used to explore the biological role of TLE4 in HCC cells. A xenograft model was established to confirm its effects on proliferation. Results: The protein expression levels of TLE4 were significantly down-regulated in HCC tissues compared tomore » matched adjacent normal liver tissues. In vitro, down-regulation of TLE4 in Huh7 or SMMC-7721 promoted cell proliferation and ectopical expression of TLE4 in Hep3B or Bel-7404 suppressed cell proliferation. In addition, the cell colony formation ability was enhanced after down-regulation of TLE4 expression in Huh-7 but suppressed after over-expression in Hep3B. Furthermore, down-regulation of TLE4 increased the cell invasion ability, as well as increased the expression level of Vimentin and decreased that of E-cadherin, indicating a phenotype of epithelial-mesenchymal transition (EMT) in HCC cells. On the contrary, ectopical expression of TLE4 in HCC cells decreased the cell invasion ability and inhibited EMT. In vivo, compared to control group, xenograft tumor volumes were significantly decreased in TLE4 overexpression group. Conclusions: These results demonstrated that TLE4 might play important regulatory roles in cellular proliferation and EMT process in HCC. - Highlights: • TLE4 is significantly down-regulated in HCC samples. • Down regulated of TLE4 in HCC cells promotes cell proliferation. • Down regulated of TLE4 in HCC cells promotes epithelial-to-mesenchymal transition.« less

Temporal lobe epilepsy: analysis of patients with dual pathology.

PubMed

Salanova, V; Markand, O; Worth, R

2004-02-01

To determine the frequency and types of dual pathology in patients with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and surgical outcome. A total of 240 patients with TLE underwent temporal resections following a comprehensive pre-surgical evaluation. Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe gliosis in association with another lesion (dual pathology). Eighteen of 37 patients with dual pathology had heterotopia of the temporal lobe, nine had cortical dysplasia, four had cavernous angiomas or arteriovenous malformations, one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic resonance imagings, 91.3% had abnormal positron emission tomography scans, and 96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed impaired memory of the epileptogenic side in 72% of the patients. Twenty patients had left and 17 had right-sided en bloc temporal resections, including the lesion and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years). 15.4% had dual pathology. The dual pathology was almost exclusively seen in patients whose lesions were congenital, or occurred early in life, suggesting that the hippocampus is more vulnerable and more readily develops HS in early childhood. Resections, including the lateral and mesial temporal structures led to a favorable outcome with no mortality and little morbidity.

Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy.

PubMed

Feng, E-S; Sui, C-B; Wang, T-X; Sun, G-L

2016-12-01

Stereotactic radiosurgery (RS) is a potential option for some patients with temporal lobe epilepsy (TLE). The aim of this meta-analysis was to determine the pooled seizure-free rate and the time interval to seizure cessation in patients with lesions in the mesial temporal lobe, and who were eligible for either stereotactic or gamma knife RS. We searched the Medline, Cochrane, EMBASE, and Google Scholar databases using combinations of the following terms: RS, stereotactic radiosurgery, gamma knife, and TLE. We screened 103 articles and selected 13 for inclusion in the meta-analysis. Significant study heterogeneity was detected; however, the included studies displayed an acceptable level of quality. We show that approximately half of the patients were seizure free over a follow-up period that ranged from 6 months to 9 years [pooled estimate: 50.9% (95% confidence interval: 0.381-0.636)], with an average of 14 months to seizure cessation [pooled estimate: 14.08 months (95% confidence interval: 11.95-12.22 months)]. Nine of 13 included studies reported data for adverse events (AEs), which included visual field deficits and headache (the two most common AEs), verbal memory impairment, psychosis, psychogenic non-epileptic seizures, and dysphasia. Patients in the individual studies experienced AEs at rates that ranged from 8%, for non-epileptic seizures, to 85%, for headache. Our findings indicate that RS may have similar or slightly less efficacy in some patients compared with invasive surgery. Randomized controlled trials of both treatment regimens should be undertaken to generate an evidence base for patient decision-making. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.

PubMed

Wang, Z; Chen, Y; Lü, Y; Chen, X; Cheng, L; Mi, X; Xu, X; Deng, W; Zhang, Y; Wang, N; Li, J; Li, Y; Wang, X

2015-08-06

JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Split exponential track length estimator for Monte-Carlo simulations of small-animal radiation therapy

NASA Astrophysics Data System (ADS)

Smekens, F.; Létang, J. M.; Noblet, C.; Chiavassa, S.; Delpon, G.; Freud, N.; Rit, S.; Sarrut, D.

2014-12-01

We propose the split exponential track length estimator (seTLE), a new kerma-based method combining the exponential variant of the TLE and a splitting strategy to speed up Monte Carlo (MC) dose computation for low energy photon beams. The splitting strategy is applied to both the primary and the secondary emitted photons, triggered by either the MC events generator for primaries or the photon interactions generator for secondaries. Split photons are replaced by virtual particles for fast dose calculation using the exponential TLE. Virtual particles are propagated by ray-tracing in voxelized volumes and by conventional MC navigation elsewhere. Hence, the contribution of volumes such as collimators, treatment couch and holding devices can be taken into account in the dose calculation. We evaluated and analysed the seTLE method for two realistic small animal radiotherapy treatment plans. The effect of the kerma approximation, i.e. the complete deactivation of electron transport, was investigated. The efficiency of seTLE against splitting multiplicities was also studied. A benchmark with analog MC and TLE was carried out in terms of dose convergence and efficiency. The results showed that the deactivation of electrons impacts the dose at the water/bone interface in high dose regions. The maximum and mean dose differences normalized to the dose at the isocenter were, respectively of 14% and 2% . Optimal splitting multiplicities were found to be around 300. In all situations, discrepancies in integral dose were below 0.5% and 99.8% of the voxels fulfilled a 1%/0.3 mm gamma index criterion. Efficiency gains of seTLE varied from 3.2 × 105 to 7.7 × 105 compared to analog MC and from 13 to 15 compared to conventional TLE. In conclusion, seTLE provides results similar to the TLE while increasing the efficiency by a factor between 13 and 15, which makes it particularly well-suited to typical small animal radiation therapy applications.

White matter alterations in temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Diniz, P. B.; Salmon, C. E.; Velasco, T. R.; Sakamoto, A. C.; Leite, J. P.; Santos, A. C.

2011-03-01

In This study, we used Fractional anisotropy (FA), mean diffusivity (D), parallel diffusivity (D//) and perpendicular diffusivity (D), to localize the regions where occur axonal lesion and demyelization. TBSS was applied to analyze the FA data. After, the regions with alteration were studied with D, D// and D maps. Patients exhibited widespread degradation of FA. With D, D// and D maps analysis we found alterations in corpus callosum, corticospinal tract, fornix, internal capsule, corona radiate, Sagittal stratum, cingulum, fronto-occipital fasciculus and uncinate fasciculus. Our results are consistent with the hypothesis that exist demyelization and axonal damage in patients with TLE.

Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

PubMed

Wong, Shi-Bing; Cheng, Sin-Jhong; Hung, Wei-Chen; Lee, Wang-Tso; Min, Ming-Yuan

2015-01-01

Peroxisomal proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA) receptor-mediated temporal lobe epilepsy (TLE). We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC) analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy.

PubMed

Pottoo, Faheem Hyder; Tabassum, Nahida; Javed, Md Noushad; Nigar, Shah; Rasheed, Rouqia; Khan, Ayash; Barkat, Md Abul; Alam, Md Sabir; Maqbool, Amir; Ansari, Mohammad Azam; Barreto, George E; Ashraf, Ghulam Md

2018-06-07

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i.p). The response was stalked for intensive behavioral monitoring of convulsions, hippocampal neuropeptide Y (NPY), and oxidative stress discernment along with histomorphological studies. The resultant data confirmed the therapeutic potential of triple drug combination of raloxifene (4 mg/kg) with fluoxetine (14 mg/kg) and bromocriptine (6 mg/kg) compared to monotherapy with raloxifene (4 mg/kg), and bromocriptine (6 mg/kg) as otherwise monotherapy with fluoxetine (14 mg/kg) was ineffective to suppress convulsions; an effect better than sodium valproate (300 mg/kg), a standard AED, was validated. Most profoundly, PILO-induced compensatory increases in hippocampal NPY levels (20.01%), which was escalated (100%) with the triple drug combination. The same pattern of results was superseded for oxidative stress indices and neuronal damage. The results for the first time demonstrate the propitious role of triple drug combination in the management of SE and TLE. Therapeutically, this enhancing profile of drugs fosters a safer and more effective drug-combination regimen. Graphical abstract ᅟ.

Detection of Intracranial Signatures of Interictal Epileptiform Discharges from Concurrent Scalp EEG.

PubMed

Spyrou, Loukianos; Martín-Lopez, David; Valentín, Antonio; Alarcón, Gonzalo; Sanei, Saeid

2016-06-01

Interictal epileptiform discharges (IEDs) are transient neural electrical activities that occur in the brain of patients with epilepsy. A problem with the inspection of IEDs from the scalp electroencephalogram (sEEG) is that for a subset of epileptic patients, there are no visually discernible IEDs on the scalp, rendering the above procedures ineffective, both for detection purposes and algorithm evaluation. On the other hand, intracranially placed electrodes yield a much higher incidence of visible IEDs as compared to concurrent scalp electrodes. In this work, we utilize concurrent scalp and intracranial EEG (iEEG) from a group of temporal lobe epilepsy (TLE) patients with low number of scalp-visible IEDs. The aim is to determine whether by considering the timing information of the IEDs from iEEG, the resulting concurrent sEEG contains enough information for the IEDs to be reliably distinguished from non-IED segments. We develop an automatic detection algorithm which is tested in a leave-subject-out fashion, where each test subject's detection algorithm is based on the other patients' data. The algorithm obtained a [Formula: see text] accuracy in recognizing scalp IED from non-IED segments with [Formula: see text] accuracy when trained and tested on the same subject. Also, it was able to identify nonscalp-visible IED events for most patients with a low number of false positive detections. Our results represent a proof of concept that IED information for TLE patients is contained in scalp EEG even if they are not visually identifiable and also that between subject differences in the IED topology and shape are small enough such that a generic algorithm can be used.

Hippocampal distribution of vesicular glutamate transporter 1 in patients with temporal lobe epilepsy.

PubMed

van der Hel, W Saskia; Verlinde, Suzanne A M W; Meijer, Dimphna H M; de Wit, Marina; Rensen, Marije G; van Gassen, Koen L I; van Rijen, Peter C; van Veelen, Cees W M; de Graan, Pierre N E

2009-07-01

Vesicular glutamate transporters (VGLUTs) are responsible for loading synaptic vesicles with glutamate, determining the phenotype of glutamatergic neurons, and have been implicated in the regulation of quantal size and presynaptic plasticity. We analyzed VGLUT subtype expression in normal human hippocampus and tested the hypothesis that alterations in VGLUT expression may contribute to long-term changes in glutamatergic transmission reported in patients with temporal lobe epilepsy (TLE). VGLUT immunohistochemistry, immunofluorescence, in situ hybridization, Western blotting, and quantitative polymerase chain reaction (qPCR) were performed on biopsies from TLE patients without (non-HS) and with hippocampal sclerosis (HS) and compared to autopsy controls and rat hippocampus. VGLUT1 expression was compared with synaptophysin, neuropeptide Y (NPY), and Timm's staining. VGLUT1 was the predominant VGLUT in human hippocampus and appeared to be localized to presynaptic glutamatergic terminals. In non-HS hippocampi, VGLUT1 protein levels were increased compared to control and HS hippocampi in all subfields. In HS hippocampi VGLUT1 expression was decreased in subfields with severe neuronal loss, but strongly up-regulated in the dentate gyrus, characterized by mossy fiber sprouting. VGLUT1 is used as marker for glutamatergic synapses in the human hippocampus. In HS hippocampi VGLUT1 up-regulation in the dentate gyrus probably marks new glutamatergic synapses formed by mossy fiber sprouting. Our data indicate that non-HS patients have an increased capacity to store glutamate in vesicles, most likely due to an increase in translational processes or upregulation of VGLUT1 in synapses from afferent neurons outside the hippocampus. This up-regulation may increase glutamatergic transmission, and thus contribute to increased extracellular glutamate levels and hyperexcitability.

Altered mitochondrial acetylation profiles in a kainic acid model of temporal lobe epilepsy.

PubMed

Gano, Lindsey B; Liang, Li-Ping; Ryan, Kristen; Michel, Cole R; Gomez, Joe; Vassilopoulos, Athanassios; Reisdorph, Nichole; Fritz, Kristofer S; Patel, Manisha

2018-08-01

Impaired bioenergetics and oxidative damage in the mitochondria are implicated in the etiology of temporal lobe epilepsy, and hyperacetylation of mitochondrial proteins has recently emerged as a critical negative regulator of mitochondrial functions. However, the roles of mitochondrial acetylation and activity of the primary mitochondrial deacetylase, SIRT3, have not been explored in acquired epilepsy. We investigated changes in mitochondrial acetylation and SIRT3 activity in the development of chronic epilepsy in the kainic acid rat model of TLE. Hippocampal measurements were made at 48 h, 1 week and 12 weeks corresponding to the acute, latent and chronic stages of epileptogenesis. Assessment of hippocampal bioenergetics demonstrated a ≥ 27% decrease in the ATP/ADP ratio at all phases of epileptogenesis (p < 0.05), whereas cellular NAD+ levels were decreased by ≥ 41% in the acute and latent time points (p < 0.05), but not in chronically epileptic rats. In spontaneously epileptic rats, we found decreased protein expression of SIRT3 and a 60% increase in global mitochondrial acetylation, as well as enhanced acetylation of the known SIRT3 substrates MnSOD, Ndufa9 of Complex I and IDH2 (all p < 0.05), suggesting SIRT3 dysfunction in chronic epilepsy. Mass spectrometry-based acetylomics investigation of hippocampal mitochondria demonstrated a 79% increase in unique acetylated proteins from rats in the chronic phase vs. controls. Pathway analysis identified numerous mitochondrial bioenergetic pathways affected by mitochondrial acetylation. These results suggest SIRT3 dysfunction and aberrant protein acetylation may contribute to mitochondrial dysfunction in chronic epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Postictal psychosis and its electrophysiological correlates in invasive EEG: a case report study and literature review.

PubMed

Kuba, Robert; Brázdil, Milan; Rektor, Ivan

2012-04-01

We identified two patients with medically refractory temporal lobe epilepsy, from whom intracranial EEG recordings were obtained at the time of postictal psychosis. Both patients had mesial temporal epilepsy associated with hippocampal sclerosis. In both patients, the postictal psychosis was associated with a continual "epileptiform" EEG pattern that differed from their interictal and ictal EEG findings (rhythmical slow wave and "abortive" spike-slow wave complex activity in the right hippocampus and lateral temporal cortex in case 1 and a periodic pattern of triphasic waves in the contacts recording activity from the left anterior cingulate gyrus). Some cases of postictal psychosis might be caused by the transient impairment of several limbic system structures due to the "continual epileptiform discharge" in some brain regions. Case 2 is the first report of a patient with TLE in whom psychotic symptoms were associated with the epileptiform impairment of the anterior cingulate gyrus. Copyright © 2012 Elsevier Inc. All rights reserved.

Nonlinear Directed Interactions Between HRV and EEG Activity in Children With TLE.

PubMed

Schiecke, Karin; Pester, Britta; Piper, Diana; Benninger, Franz; Feucht, Martha; Leistritz, Lutz; Witte, Herbert

2016-12-01

Epileptic seizure activity influences the autonomic nervous system (ANS) in different ways. Heart rate variability (HRV) is used as indicator for alterations of the ANS. It was shown that linear, nondirected interactions between HRV and EEG activity before, during, and after epileptic seizure occur. Accordingly, investigations of directed nonlinear interactions are logical steps to provide, e.g., deeper insight into the development of seizure onsets. Convergent cross mapping (CCM) investigates nonlinear, directed interactions between time series by using nonlinear state space reconstruction. CCM is applied to simulated and clinically relevant data, i.e., interactions between HRV and specific EEG components of children with temporal lobe epilepsy (TLE). In addition, time-variant multivariate Autoregressive model (AR)-based estimation of partial directed coherence (PDC) was performed for the same data. Influence of estimation parameters and time-varying behavior of CCM estimation could be demonstrated by means of simulated data. AR-based estimation of PDC failed for the investigation of our clinical data. Time-varying interval-based application of CCM on these data revealed directed interactions between HRV and delta-related EEG activity. Interactions between HRV and alpha-related EEG activity were visible but less pronounced. EEG components mainly drive HRV. The interaction pattern and directionality clearly changed with onset of seizure. Statistical relevant interactions were quantified by bootstrapping and surrogate data approach. In contrast to AR-based estimation of PDC CCM was able to reveal time-courses and frequency-selective views of nonlinear interactions for the further understanding of complex interactions between the epileptic network and the ANS in children with TLE.

Face-name association task reveals memory networks in patients with left and right hippocampal sclerosis.

PubMed

Klamer, Silke; Milian, Monika; Erb, Michael; Rona, Sabine; Lerche, Holger; Ethofer, Thomas

2017-01-01

We aimed to identify reorganization processes of episodic memory networks in patients with left and right temporal lobe epilepsy (TLE) due to hippocampal sclerosis as well as their relations to neuropsychological memory performance. We investigated 28 healthy subjects, 12 patients with left TLE (LTLE) and 9 patients with right TLE (RTLE) with hippocampal sclerosis by means of functional magnetic resonance imaging (fMRI) using a face-name association task, which combines verbal and non-verbal memory functions. Regions-of-interest (ROIs) were defined based on the group results of the healthy subjects. In each ROI, fMRI activations were compared across groups and correlated with verbal and non-verbal memory scores. The face-name association task yielded activations in bilateral hippocampus (HC), left inferior frontal gyrus (IFG), left superior frontal gyrus (SFG), left superior temporal gyrus, bilateral angular gyrus (AG), bilateral medial prefrontal cortex and right anterior temporal lobe (ATL). LTLE patients demonstrated significantly less activation in the left HC and left SFG, whereas RTLE patients showed significantly less activation in the HC bilaterally, the left SFG and right AG. Verbal memory scores correlated with activations in the left and right HC, left SFG and right ATL and non-verbal memory scores with fMRI activations in the left and right HC and left SFG. The face-name association task can be employed to examine functional alterations of hippocampal activation during encoding of both verbal and non-verbal material in one fMRI paradigm. Further, the left SFG seems to be a convergence region for encoding of verbal and non-verbal material.

Losartan suppresses the kainate-induced changes of angiotensin AT1 receptor expression in a model of comorbid hypertension and epilepsy.

PubMed

Atanasova, Dimitrinka; Tchekalarova, Jana; Ivanova, Natasha; Nenchovska, Zlatina; Pavlova, Ekaterina; Atanassova, Nina; Lazarov, Nikolai

2018-01-15

Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT 1 receptor) in limbic structures, as well as the effect of the AT1 receptor antagonist losartan in a model of comorbid hypertension and epilepsy. The expression of AT 1 receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE). The effect of losartan was studied on AT 1 receptor expression in epileptic rats that were treated for a period of 4weeks after status epilepticus. The naive and epileptic SHRs were characterized by stronger protein expression of AT 1 receptor than normotensive Wistar rats in the CA1, CA3a, CA3b, CA3c field and the hilus of the dentate gyrus of the dorsal hippocampus but fewer cells were immunostained in the piriform cortex. Increased AT 1 immunostaining was observed in the basolateral amygdala of epileptic SHRs but not of epileptic Wistar rats. Losartan exerted stronger and structure-dependent suppression of AT 1 receptor expression in SHRs compared to Wistar rats. Our results confirm the important role of AT 1 receptor in epilepsy and suggest that the AT 1 receptor antagonists could be used as a therapeutic strategy for treatment of comorbid hypertension and epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Temporal lobe volume predicts Wada memory test performance in patients with mesial temporal sclerosis.

PubMed

Ding, Kan; Gong, Yunhua; Modur, Pradeep N; Diaz-Arrastia, Ramon; Agostini, Mark; Gupta, Puneet; McColl, Roderick; Hays, Ryan; Van Ness, Paul

2016-02-01

The Wada test is widely used in the presurgical evaluation of potential temporal lobectomy patients to predict postoperative memory function. Expected asymmetry (EA), defined as Wada memory lateralized to the nonsurgical hemisphere, or a higher score after injection of the surgical hemisphere would be considered favorable in terms of postoperative memory outcome. However, in some cases, nonlateralized memory (NM) results, with no appreciable asymmetry, may occur because of impaired scores after both injections, often leading to denial of surgery. The reason for such nonlateralized Wada memory in patients with intractable temporal lobe epilepsy (TLE) remains unclear. Given that quantitative morphometric magnetic resonance imaging studies in TLE patients have shown bilateral regional atrophy in temporal and extratemporal structures, we hypothesized that the volume loss in contralateral temporal structures could contribute to nonlateralized Wada memory performance. To investigate this, we examined the relationship between the volume changes of temporal structures and Wada memory scores in patients with intractable TLE with mesial temporal sclerosis (MTS) using an age- and gender-matched control group. Memory was considered nonlateralized if the absolute difference in the total correct recall scores between ipsilateral and contralateral injections was <11%. Among 21 patients, Wada memory was lateralized in 15 and nonlateralized in 6 patients, with all the nonlateralized scores being observed in left TLE. The recall scores after ipsilateral injection were significantly lower in patients with an NM profile than an EA profile (23 ± 14% vs. 59 ± 18% correct recall, p ≤ 0.001). However, the recall scores after contralateral injection were low but similar between the two groups (25 ± 17% vs. 25 ± 15% correct recall, p=0.97). Compared to controls, all the patients showed greater volume loss in the temporal regions. However, patients with a NM profile showed significantly more volume loss than those with a lateralized memory profile in both contralateral and ipsilateral temporal regions (p<0.05). Left hemispheric Wada memory performance correlated positively with the size of the left mesial and neocortical temporal structures (r=0.49-0.63, p=0.005-0.04). Our study suggests that volume loss in the nonsurgical temporal structures is associated with nonlateralized Wada memory results in patients with intractable TLE. Copyright © 2015 Elsevier B.V. All rights reserved.

Ligands for Ionotropic Glutamate Receptors

PubMed Central

Swanson, Geoffrey T.; Sakai, Ryuichi

2010-01-01

Marine-derived small molecules and peptides have played a central role in elaborating pharmacological specificities and neuronal functions of mammalian ionotropic glutamate receptors (iGluRs), the primary mediators of excitatory synaptic transmission in the central nervous system (CNS). As well, the pathological sequelae elicited by one class of compounds (the kainoids) constitute a widely-used animal model for human mesial temporal lobe epilepsy (mTLE). New and existing molecules could prove useful as lead compounds for the development of therapeutics for neuropathologies that have aberrant glutamatergic signaling as a central component. In this chapter we discuss natural source origins and pharmacological activities of those marine compounds that target ionotropic glutamate receptors. PMID:19184587

Ligands for Ionotropic Glutamate Receptors

NASA Astrophysics Data System (ADS)

Swanson, Geoffrey T.; Sakai, Ryuichi

Marine-derived small molecules and peptides have played a central role in elaborating pharmacological specificities and neuronal functions of mammalian ionotropic glutamate receptors (iGluRs), the primary mediators of excitatory syn-aptic transmission in the central nervous system (CNS). As well, the pathological sequelae elicited by one class of compounds (the kainoids) constitute a widely-used animal model for human mesial temporal lobe epilepsy (mTLE). New and existing molecules could prove useful as lead compounds for the development of therapeutics for neuropathologies that have aberrant glutamatergic signaling as a central component. In this chapter we discuss natural source origins and pharmacological activities of those marine compounds that target ionotropic glutamate receptors.

Imbalance of community structures in epilepsy

NASA Astrophysics Data System (ADS)

Ortega, G. J.; Herrera Peco, I.; García de Sola, R.; Pastor, J.

2010-09-01

Epilepsy is commonly associated with synchronous activity in the form of spikes and also in developed seizures. Desynchronised activity seems to play an important role also in the seizure process, favouring the initiation of seizures. The aim of the present work is to explore synchronization activity in the inner areas in the temporal lobe of epileptic patients by a novel approach. Two temporal lobe epilepsy (TLE) patients' records have been analyzed through a cluster analysis. Electrical activity in the inner part of the temporal has been recorded by using Foramen Ovale Electrodes (FOE), a semi-invasive technique frequently used in drug resistant epileptic patients. Instead of tracking synchronized activity, we give here special attention to desynchronized activity, mainly those areas which are not included in synchronization clusters. Our results show that electrical activity in the epileptic side behaves in a less cohesive fashion than the contra-lateral side. There exists a clear tendency in the epileptic side to be organized as isolated clusters of electrical activity as compared with the contra-lateral side, which is organized in the form of large clusters of synchronous activity. In particular, we shall give special attention to the cluster desynchronization during the seizures. As we shall show, our results can help in understand several characteristics of the seizures dynamics.

A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

PubMed Central

Morales, Juan Carlos; Álvarez-Ferradas, Carla; Roncagliolo, Manuel; Fuenzalida, Marco; Wellmann, Mario; Nualart, Francisco Javier; Bonansco, Christian

2014-01-01

Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental models of epilepsy. PMID:25100948

A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats.

PubMed

Morales, Juan Carlos; Alvarez-Ferradas, Carla; Roncagliolo, Manuel; Fuenzalida, Marco; Wellmann, Mario; Nualart, Francisco Javier; Bonansco, Christian

2014-01-01

Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK), the rapid kindling types (RK) described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and immunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE) which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA) stimulation with 10 trains of biphasic pulses (10 s; 50 Hz) per day with 20 min-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through electroencephalographic (EEG) recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental models of epilepsy.

Childhood temporal lobe epilepsy: correlation between electroencephalography and magnetic resonance spectroscopy: a case-control study.

PubMed

Azab, Seham Fa; Sherief, Laila M; Saleh, Safaa H; Elshafeiy, Mona M; Siam, Ahmed G; Elsaeed, Wafaa F; Arafa, Mohamed A; Bendary, Eman A; Sherbiny, Hanan S; Elbehedy, Rabab M; Aziz, Khalid A

2015-04-18

The diagnosis of epilepsy should be made as early as possible to give a child the best chance for treatment success and also to decrease complications such as learning difficulties and social and behavioral problems. In this study, we aimed to assess the ability of magnetic resonance spectroscopy (MRS) in detecting the lateralization side in patients with Temporal lobe epilepsy (TLE) in correlation with EEG and MRI findings. This was a case-control study including 40 patients diagnosed (clinically and by EEG) as having temporal lobe epilepsy aged 8 to 14 years (mean, 10.4 years) and 20 healthy children with comparable age and gender as the control group. All patients were subjected to clinical examination, interictal electroencephalography and magnetic resonance imaging (MRI). Proton magnetic resonance spectroscopic examination (MRS) was performed to the patients and the controls. According to the findings of electroencephalography, our patients were classified to three groups: Group 1 included 20 patients with unitemporal (lateralized) epileptic focus, group 2 included 12 patients with bitemporal (non-lateralized) epileptic focus and group 3 included 8 patients with normal electroencephalography. Magnetic resonance spectroscopy could lateralize the epileptic focus in 19 patients in group 1, nine patients in group2 and five patients in group 3 with overall lateralization of (82.5%), while electroencephalography was able to lateralize the focus in (50%) of patients and magnetic resonance imaging detected lateralization of mesial temporal sclerosis in (57.5%) of patients. Magnetic resonance spectroscopy is a promising tool in evaluating patients with epilepsy and offers increased sensitivity to detect temporal pathology that is not obvious on structural MRI imaging.

Subventricular Zone-Derived Neural Stem Cell Grafts Protect Against Hippocampal Degeneration and Restore Cognitive Function in the Mouse Following Intrahippocampal Kainic Acid Administration

PubMed Central

Miltiadous, Panagiota; Kouroupi, Georgia; Stamatakis, Antonios; Koutsoudaki, Paraskevi N.

2013-01-01

Temporal lobe epilepsy (TLE) is a major neurological disease, often associated with cognitive decline. Since approximately 30% of patients are resistant to antiepileptic drugs, TLE is being considered as a possible clinical target for alternative stem cell-based therapies. Given that insulin-like growth factor I (IGF-I) is neuroprotective following a number of experimental insults to the nervous system, we investigated the therapeutic potential of neural stem/precursor cells (NSCs) transduced, or not, with a lentiviral vector for overexpression of IGF-I after transplantation in a mouse model of kainic acid (KA)-induced hippocampal degeneration, which represents an animal model of TLE. Exposure of mice to the Morris water maze task revealed that unilateral intrahippocampal NSC transplantation significantly prevented the KA-induced cognitive decline. Moreover, NSC grafting protected against neurodegeneration at the cellular level, reduced astrogliosis, and maintained endogenous granule cell proliferation at normal levels. In some cases, as in the reduction of hippocampal cell loss and the reversal of the characteristic KA-induced granule cell dispersal, the beneficial effects of transplanted NSCs were manifested earlier and were more pronounced when these were transduced to express IGF-I. However, differences became less pronounced by 2 months postgrafting, since similar amounts of IGF-I were detected in the hippocampi of both groups of mice that received cell transplants. Grafted NSCs survived, migrated, and differentiated into neurons—including glutamatergic cells—and not glia, in the host hippocampus. Our results demonstrate that transplantation of IGF-I producing NSCs is neuroprotective and restores cognitive function following KA-induced hippocampal degeneration. PMID:23417642

Establishing a Mathematical Equations and Improving the Production of L-tert-Leucine by Uniform Design and Regression Analysis.

PubMed

Jiang, Wei; Xu, Chao-Zhen; Jiang, Si-Zhi; Zhang, Tang-Duo; Wang, Shi-Zhen; Fang, Bai-Shan

2017-04-01

L-tert-Leucine (L-Tle) and its derivatives are extensively used as crucial building blocks for chiral auxiliaries, pharmaceutically active ingredients, and ligands. Combining with formate dehydrogenase (FDH) for regenerating the expensive coenzyme NADH, leucine dehydrogenase (LeuDH) is continually used for synthesizing L-Tle from α-keto acid. A multilevel factorial experimental design was executed for research of this system. In this work, an efficient optimization method for improving the productivity of L-Tle was developed. And the mathematical model between different fermentation conditions and L-Tle yield was also determined in the form of the equation by using uniform design and regression analysis. The multivariate regression equation was conveniently implemented in water, with a space time yield of 505.9 g L -1  day -1 and an enantiomeric excess value of >99 %. These results demonstrated that this method might become an ideal protocol for industrial production of chiral compounds and unnatural amino acids such as chiral drug intermediates.

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

PubMed Central

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden itself. The divergences in disease progression and seizure outcome, in addition to the histopathological dissimilarities, further substantiate the existence of strain differences for the KASE rat model of TLE. PMID:29163349

Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy

PubMed Central

Franco-Villanueva, Ana; Romancheck, Christian; Morano, Rachel L.; Smith, Brittany L.; Packard, Benjamin A.; Danzer, Steve C.; Herman, James P.

2018-01-01

Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy. PMID:29795651

Functional disruption of stress modulatory circuits in a model of temporal lobe epilepsy.

PubMed

Wulsin, Aynara C; Franco-Villanueva, Ana; Romancheck, Christian; Morano, Rachel L; Smith, Brittany L; Packard, Benjamin A; Danzer, Steve C; Herman, James P

2018-01-01

Clinical data suggest that the neuroendocrine stress response is chronically dysregulated in a subset of patients with temporal lobe epilepsy (TLE), potentially contributing to both disease progression and the development of psychiatric comorbidities such as anxiety and depression. Whether neuroendocrine dysregulation and psychiatric comorbidities reflect direct effects of epilepsy-related pathologies, or secondary effects of disease burden particular to humans with epilepsy (i.e. social estrangement, employment changes) is not clear. Animal models provide an opportunity to dissociate these factors. Therefore, we queried whether epileptic mice would reproduce neuroendocrine and behavioral changes associated with human epilepsy. Male FVB mice were exposed to pilocarpine to induce status epilepticus (SE) and the subsequent development of spontaneous recurrent seizures. Morning baseline corticosterone levels were elevated in pilocarpine treated mice at 1, 7 and 10 weeks post-SE relative to controls. Similarly, epileptic mice had increased adrenal weight when compared to control mice. Exposure to acute restraint stress resulted in hypersecretion of corticosterone 30 min after the onset of the challenge. Anatomical analyses revealed reduced Fos expression in infralimbic and prelimbic prefrontal cortex, ventral subiculum and basal amygdala following restraint. No differences in Fos immunoreactivity were found in the paraventricular nucleus of the hypothalamus, hippocampal subfields or central amygdala. In order to assess emotional behavior, a second cohort of mice underwent a battery of behavioral tests, including sucrose preference, open field, elevated plus maze, 24h home-cage monitoring and forced swim. Epileptic mice showed increased anhedonic behavior, hyperactivity and anxiety-like behaviors. Together these data demonstrate that epileptic mice develop HPA axis hyperactivity and exhibit behavioral dysfunction. Endocrine and behavioral changes are associated with impaired recruitment of forebrain circuits regulating stress inhibition and emotional reactivity. Loss of forebrain control may underlie pronounced endocrine dysfunction and comorbid psychopathologies seen in temporal lobe epilepsy.

Properties of single NMDA receptor channels in human dentate gyrus granule cells

PubMed Central

Lieberman, David N; Mody, Istvan

1999-01-01

Cell-attached single-channel recordings of NMDA channels were carried out in human dentate gyrus granule cells acutely dissociated from slices prepared from hippocampi surgically removed for the treatment of temporal lobe epilepsy (TLE). The channels were activated by l-aspartate (250–500 nm) in the presence of saturating glycine (8 μm). The main conductance was 51 ± 3 pS. In ten of thirty granule cells, clear subconductance states were observed with a mean conductance of 42 ± 3 pS, representing 8 ± 2% of the total openings. The mean open times varied from cell to cell, possibly owing to differences in the epileptogenicity of the tissue of origin. The mean open time was 2.70 ± 0.95 ms (range, 1.24–4.78 ms). In 87% of the cells, three exponential components were required to fit the apparent open time distributions. In the remaining neurons, as in control rat granule cells, two exponentials were sufficient. Shut time distributions were fitted by five exponential components. The average numbers of openings in bursts (1.74 ± 0.09) and clusters (3.06 ± 0.26) were similar to values obtained in rodents. The mean burst (6.66 ± 0.9 ms), cluster (20.1 ± 3.3 ms) and supercluster lengths (116.7 ± 17.5 ms) were longer than those in control rat granule cells, but approached the values previously reported for TLE (kindled) rats. As in rat NMDA channels, adjacent open and shut intervals appeared to be inversely related to each other, but it was only the relative areas of the three open time constants that changed with adjacent shut time intervals. The long openings of human TLE NMDA channels resembled those produced by calcineurin inhibitors in control rat granule cells. Yet the calcineurin inhibitor FK-506 (500 nm) did not prolong the openings of human channels, consistent with a decreased calcineurin activity in human TLE. Many properties of the human NMDA channels resemble those recorded in rat hippocampal neurons. Both have similar slope conductances, five exponential shut time distributions, complex groupings of openings, and a comparable number of openings per grouping. Other properties of human TLE NMDA channels correspond to those observed in kindling; the openings are considerably long, requiring an additional exponential component to fit their distributions, and inhibition of calcineurin is without effect in prolonging the openings. PMID:10373689

Corepressors TLE1 and TLE3 interact with HESX1 and PROP1.

PubMed

Carvalho, Luciani R; Brinkmeier, Michelle L; Castinetti, Frederic; Ellsworth, Buffy S; Camper, Sally A

2010-04-01

Pituitary hormone deficiency causes short stature in one in 4000 children born and can be caused by mutations in transcription factor genes, including HESX1, PROP1, and POU1F1. HESX1 interacts with a member of the groucho-related gene family, TLE1, through an engrailed homology domain and represses PROP1 activity. Mice with Prop1 deficiency exhibit failed differentiation of the POU1F1 lineage, resulting in lack of TSH, GH, and prolactin. In addition, these mutants exhibit profound pituitary dysmorphology and excess Hesx1 and Tle3 expression. The ability of HESX1 to interact with TLE3 has not been explored previously. We tested the ability of TLE3 to enhance HESX1-mediated repression of PROP1 in cell culture. Both TLE3 and TLE1 repress PROP1 in conjunction with HESX1 with similar efficiencies. TLE1 and TLE3 can each repress PROP1 in the absence of HESX1 via a protein-protein interaction. We tested the functional consequences of ectopic TLE3 and HESX1 expression in transgenic mice by driving constitutive expression in pituitary thyrotrophs and gonadotrophs. Terminal differentiation of these cells was suppressed by HESX1 alone and by TLE3 and HESX1 together but not by TLE3 alone. In summary, we present evidence that HESX1 is a strong repressor that can be augmented by the corepressors TLE1 and TLE3. Our in vitro studies suggest that TLE1 and TLE3 might also play roles independent of HESX1 by interacting with other transcription factors like PROP1.

JNK1 inhibition by Licochalcone A leads to neuronal protection against excitotoxic insults derived of kainic acid.

PubMed

Busquets, Oriol; Ettcheto, Miren; Verdaguer, Ester; Castro-Torres, Ruben D; Auladell, Carme; Beas-Zarate, Carlos; Folch, Jaume; Camins, Antoni

2018-03-15

The mitogen-activated protein kinase family (MAPK) is an important group of enzymes involved in cellular responses to diverse external stimuli. One of the members of this family is the c-Jun-N-terminal kinase (JNK). The activation of the JNK pathway has been largely associated with the pathogenesis that occurs in epilepsy and neurodegeneration. Kainic acid (KA) administration in rodents is an experimental approach that induces status epilepticus (SE) and replicates many of the phenomenological features of human temporal lobe epilepsy (TLE). Recent studies in our group have evidenced that the absence of the JNK1 gene has neuroprotective effects against the damage induced by KA, as it occurs with the absence of JNK3. The aim of the present study was to analyse whether the pharmacological inhibition of JNK1 by Licochalcone A (Lic-A) had similar effects and if it may be considered as a new molecule for the treatment of SE. In order to achieve this objective, animals were pre-treated with Lic-A and posteriorly administered with KA as a model for TLE. In addition, a comparative study with KA was performed between wild type pre-treated with Lic-A and single knock-out transgenic mice for the Jnk1 -/- gene. Our results showed that JNK1 inhibition by Lic-A, previous to KA administration, caused a reduction in the convulsive pattern. Furthermore, it reduced phosphorylation levels of the JNK, as well as its activity. In addition, Lic-A prevented hippocampal neuronal degeneration, increased pro-survival anti-apoptotic mechanisms, reduced pro-apoptotic biomarkers, decreased cellular stress and neuroinflammatory processes. Thus, our results suggest that inhibition of the JNK1 by Lic-A has neuroprotective effects and that; it could be a new potential approach for the treatment of SE and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional MRI of facial emotion processing in left temporal lobe epilepsy.

PubMed

Szaflarski, Jerzy P; Allendorfer, Jane B; Heyse, Heidi; Mendoza, Lucy; Szaflarski, Basia A; Cohen, Nancy

2014-03-01

Temporal lobe epilepsy (TLE) may negatively affect the ability to recognize emotions. This study aimed to determine the cortical correlates of facial emotion processing (happy, sad, fearful, and neutral) in patients with well-characterized left TLE (LTLE) and to examine the effect of seizure control on emotion processing. We enrolled 34 consecutive patients with LTLE and 30 matched healthy control (HC) subjects. Participants underwent functional MRI (fMRI) with an event-related facial emotion recognition task. The seizures of seventeen patients were controlled (no seizure in at least 3months; LTLE-sz), and 17 continued to experience frequent seizures (LTLE+sz). Mood was assessed with the Beck Depression Inventory (BDI) and the Profile of Mood States (POMS). There were no differences in demographic characteristics and measures of mood between HC subjects and patients with LTLE. In patients with LTLE, fMRI showed decreased blood oxygenation level dependent (BOLD) signal in the hippocampus/parahippocampus and cerebellum in processing of happy faces and increased BOLD signal in occipital regions in response to fearful faces. Comparison of groups with LTLE+sz and LTLE-sz showed worse BDI and POMS scores in LTLE+sz (all p<0.05) except for POMS tension/anxiety (p=0.067). Functional MRI revealed increased BOLD signal in patients with LTLE+sz in the left precuneus and left parahippocampus for "fearful" faces and in the left periarcheocortex for "neutral" faces. There was a correlation between the fMRI and Total Mood Disturbance in the left precuneus in LTLE-sz (p=0.019) and in LTLE+sz (p=0.018). Overall, LTLE appears to have a relatively minor effect on the cortical underpinnings of facial emotion processing, while the effect of seizure state (controlled vs. not controlled) is more pronounced, indicating a significant relationship between seizure control and emotion processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Different effects of anterior temporal lobectomy and selective amygdalohippocampectomy on verbal memory performance of patients with epilepsy.

PubMed

Boucher, Olivier; Dagenais, Emmanuelle; Bouthillier, Alain; Nguyen, Dang Khoa; Rouleau, Isabelle

2015-11-01

The advantage of selective amygdalohippocampectomy (SAH) over anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy (TLE) remains controversial. Because ATL is more extensive and involves the lateral and medial parts of the temporal lobe, it may be predicted that its impact on memory is more important than SAH, which involves resection of medial temporal structures only. However, several studies do not support this assumption. Possible explanations include task-specific factors such as the extent of semantic and syntactic information to be memorized and failure to control for main confounders. We compared preoperative vs. postoperative memory performance in 13 patients with SAH with 26 patients who underwent ATL matched on side of surgery, IQ, age at seizure onset, and age at surgery. Memory function was assessed using the Logical Memory subtest from the Wechsler Memory Scales - 3rd edition (LM-WMS), the Rey Auditory Verbal Learning Test (RAVLT), the Digit Span subtest from the Wechsler Adult Intelligence Scale, and the Rey-Osterrieth Complex Figure Test. Repeated measures analyses of variance revealed opposite effects of SAH and ATL on the two verbal learning memory tests. On the immediate recall trial of the LM-WMS, performance deteriorated after ATL in comparison with that after SAH. By contrast, on the delayed recognition trial of the RAVLT, performance deteriorated after SAH compared with that after ATL. However, additional analyses revealed that the latter finding was only observed when surgery was conducted in the right hemisphere. No interaction effects were found on other memory outcomes. The results are congruent with the view that tasks involving rich semantic content and syntactical structure are more sensitive to the effects of lateral temporal cortex resection as compared with mesiotemporal resection. The findings highlight the importance of task selection in the assessment of memory in patients undergoing TLE surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Transient reduction in theta power caused by interictal spikes in human temporal lobe epilepsy.

PubMed

Manling Ge; Jundan Guo; Yangyang Xing; Zhiguo Feng; Weide Lu; Xinxin Ma; Yuehua Geng; Xin Zhang

2017-07-01

The inhibitory impacts of spikes on LFP theta rhythms(4-8Hz) are investigated around sporadic spikes(SSs) based on intracerebral EEG of 4 REM sleep patients with temporal lobe epilepsy(TLE) under the pre-surgical monitoring. Sequential interictal spikes in both genesis area and extended propagation pathway are collected, that, SSs genesis only in anterior hippocampus(aH)(possible propagation pathway in Entorhinal cortex(EC)), only in EC(possible propagation pathway in aH), and in both aH and EC synchronously. Instantaneous theta power was estimated by using Gabor wavelet transform, and theta power level was estimated by averaged over time and frequency before SSs(350ms pre-spike) and after SSs(350ms post-spike). The inhibitory effect around spikes was evaluated by the ratio of theta power level difference between pre-spike and post-spike to pre-spike theta power level. The findings were that theta power level was reduced across SSs, and the effects were more sever in the case of SSs in both aH and EC synchronously than either SSs only in EC or SSs only in aH. It is concluded that interictal spikes impair LFP theta rhythms transiently and directly. The work suggests that the reduction of theta power after the interictal spike might be an evaluation indicator of damage of epilepsy to human cognitive rhythms.

Interpolation of orientation distribution functions in diffusion weighted imaging using multi-tensor model.

PubMed

Afzali, Maryam; Fatemizadeh, Emad; Soltanian-Zadeh, Hamid

2015-09-30

Diffusion weighted imaging (DWI) is a non-invasive method for investigating the brain white matter structure and can be used to evaluate fiber bundles. However, due to practical constraints, DWI data acquired in clinics are low resolution. This paper proposes a method for interpolation of orientation distribution functions (ODFs). To this end, fuzzy clustering is applied to segment ODFs based on the principal diffusion directions (PDDs). Next, a cluster is modeled by a tensor so that an ODF is represented by a mixture of tensors. For interpolation, each tensor is rotated separately. The method is applied on the synthetic and real DWI data of control and epileptic subjects. Both experiments illustrate capability of the method in increasing spatial resolution of the data in the ODF field properly. The real dataset show that the method is capable of reliable identification of differences between temporal lobe epilepsy (TLE) patients and normal subjects. The method is compared to existing methods. Comparison studies show that the proposed method generates smaller angular errors relative to the existing methods. Another advantage of the method is that it does not require an iterative algorithm to find the tensors. The proposed method is appropriate for increasing resolution in the ODF field and can be applied to clinical data to improve evaluation of white matter fibers in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Status Epilepticus

PubMed Central

Seinfeld, Syndi; Goodkin, Howard P.; Shinnar, Shlomo

2016-01-01

Although the majority of seizures are brief and cause no long-term consequences, a subset is sufficiently prolonged that long-term consequences can result. These very prolonged seizures are termed “status epilepticus” (SE) and are considered a neurological emergency. The clinical presentation of SE can be diverse. SE can occur at any age but most commonly occurs in the very young and the very old. There are numerous studies on SE in animals in which the pathophysiology, medication responses, and pathology can be rigorously studied in a controlled fashion. Human data are consistent with the animal data. In particular, febrile status epilepticus (FSE), a form of SE common in young children, is associated with injury to the hippocampus and subsequent temporal lobe epilepsy (TLE) in both animals and humans. PMID:26931807

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities.

PubMed

Wendling, Anne-Sophie; Steinhoff, Bernhard J; Bodin, Frédéric; Staack, Anke M; Zentner, Josef; Scholly, Julia; Valenti, Maria-Paula; Schulze-Bonhage, Andreas; Hirsch, Edouard

2015-03-01

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently. Copyright © 2015 Elsevier B.V. All rights reserved.

Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging.

PubMed

Lemkaddem, Alia; Daducci, Alessandro; Kunz, Nicolas; Lazeyras, François; Seeck, Margitta; Thiran, Jean-Philippe; Vulliémoz, Serge

2014-01-01

Focal epilepsy is increasingly recognized as the result of an altered brain network, both on the structural and functional levels and the characterization of these widespread brain alterations is crucial for our understanding of the clinical manifestation of seizure and cognitive deficits as well as for the management of candidates to epilepsy surgery. Tractography based on Diffusion Tensor Imaging allows non-invasive mapping of white matter tracts in vivo. Recently, diffusion spectrum imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fiber crossing and recent developments allow acquisition times compatible with clinical application. We used DSI and parcellation of the gray matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical and subcortical regions in patients with focal epilepsy and healthy controls. In addition, the high angular and radial resolution of DSI allowed us to evaluate also some of the biophysical compartment models, to better understand the cause of the changes in diffusion anisotropy. Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

Acute Seizures in Old Age Leads to a Greater Loss of CA1 Pyramidal Neurons, an Increased Propensity for Developing Chronic TLE and a Severe Cognitive Dysfunction.

PubMed

Hattiangady, Bharathi; Kuruba, Ramkumar; Shetty, Ashok K

2011-02-01

The aged population displays an enhanced risk for developing acute seizure (AS) activity. However, it is unclear whether AS activity in old age would result in a greater magnitude of hippocampal neurodegeneration and inflammation, and an increased predilection for developing chronic temporal lobe epilepsy (TLE) and cognitive dysfunction. Therefore, we addressed these issues in young-adult (5-months old) and aged (22-months old) F344 rats after three-hours of AS activity, induced through graded intraperitoneal injections of kainic acid (KA), and terminated through a diazepam injection. During the three-hours of AS activity, both young adult and aged groups exhibited similar numbers of stage-V motor seizures but the numbers of stage-IV motor seizures were greater in the aged group. In both age groups, three-hour AS activity induced degeneration of 50-55% of neurons in the dentate hilus, 22-32% of neurons in the granule cell layer and 49-52% neurons in the CA3 pyramidal cell layer without showing any interaction between the age and AS activity. However, degeneration of neurons in the CA1 pyramidal cell layer showed a clear interaction between the age and AS activity (12% in the young adult group and 56% in the aged group), suggesting that an advanced age makes the CA1 pyramidal neurons more susceptible to die with AS activity. The extent of inflammation measured through the numbers of activated microglial cells was similar between the two age groups. Interestingly, the predisposition for developing chronic TLE at 2-3 months after AS activity was 60% for young adult rats but 100% for aged rats. Moreover, both frequency & intensity of spontaneous recurrent seizures in the chronic phase after AS activity were 6-12 folds greater in aged rats than in young adult rats. Furthermore, aged rats lost their ability for spatial learning even in a scrupulous eleven-session water maze learning paradigm after AS activity, in divergence from young adult rats which retained the ability for spatial learning but had memory retrieval dysfunction after AS activity. Thus, AS activity in old age results in a greater loss of hippocampal CA1 pyramidal neurons, an increased propensity for developing robust chronic TLE, and a severe cognitive dysfunction.

Clinical and electrophysiological findings in mesial temporal lobe epilepsy with hippocampal sclerosis, based on the recent histopathological classifications.

PubMed

Tezer, F Irsel; Xasiyev, Farid; Soylemezoglu, Figen; Bilginer, Burcak; Oguz, Kader Karli; Saygi, Serap

2016-11-01

Hippocampal sclerosis (HS) is a common pathology in MTLE, patients may show different surgical outcomes and clinical features. The 2013 ILAE classification subdivides HS into 3 types (HS type 1: severe neuronal loss and gliosis predominantly in CA1 and CA4 regions; - HS type 2: CA1 predominant; HS type 3: CA4 predominant) and includes "gliosis only, as no-HS". The association of clinical and electrophysiological findings with different HS types has not been reported previously in detail. 48 patients who had undergone temporal lobectomy with amygdalohippocampectomy due to mesial TLE-HS between February 2014 and February 2016 were included. The patients were divided into five groups: patients with HS ILAE type 1, HS ILAE type 2, HS ILAE type 3, FCD type IIIa, or gliosis/no HS. The correlation between HS ILAE types and clinical/EEG findings in patients with MTLE due to HS was investigated. Of the 48 patients 30 were male. In 23 patients, the resection was on the left side (48%). Three patients had only gliosis, 25 patients had HS ILAE type 1, 7 had HS ILAE type 2, and 4 had HS ILAE type 3. Nine of the 48 patients had cortical lamination abnormalities in the temporal lobe associated with HS (FCD type IIIa). All patients were seizure free for early follow up. There was no association between type of HS in terms of duration of epilepsy, onset age of epilepsy, lateralized or localized semiological findings, or interictal/ictal EEG findings. Family history of epilepsy or SGTCSs were statistically more frequent in patients with types 2 and 3 HS and status epilepticus was more frequent in patients with HS-FCD type IIIa. The patients with HS types 2 and 3 have more frequent SGTCS or status epilepticus as well as increased family history of epilepsy. These findings can be helpful in understanding the epileptogenicity-prognoses of HS. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative complexity analysis in multi-channel intracranial EEG recordings form epilepsy brains

PubMed Central

Liu, Chang-Chia; Pardalos, Panos M.; Chaovalitwongse, W. Art; Shiau, Deng-Shan; Ghacibeh, Georges; Suharitdamrong, Wichai; Sackellares, J. Chris

2008-01-01

Epilepsy is a brain disorder characterized clinically by temporary but recurrent disturbances of brain function that may or may not be associated with destruction or loss of consciousness and abnormal behavior. Human brain is composed of more than 10 to the power 10 neurons, each of which receives electrical impulses known as action potentials from others neurons via synapses and sends electrical impulses via a sing output line to a similar (the axon) number of neurons. When neuronal networks are active, they produced a change in voltage potential, which can be captured by an electroencephalogram (EEG). The EEG recordings represent the time series that match up to neurological activity as a function of time. By analyzing the EEG recordings, we sought to evaluate the degree of underlining dynamical complexity prior to progression of seizure onset. Through the utilization of the dynamical measurements, it is possible to classify the state of the brain according to the underlying dynamical properties of EEG recordings. The results from two patients with temporal lobe epilepsy (TLE), the degree of complexity start converging to lower value prior to the epileptic seizures was observed from epileptic regions as well as non-epileptic regions. The dynamical measurements appear to reflect the changes of EEG’s dynamical structure. We suggest that the nonlinear dynamical analysis can provide a useful information for detecting relative changes in brain dynamics, which cannot be detected by conventional linear analysis. PMID:19079790

Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.

PubMed

Barron, Daniel S; Fox, Peter T; Pardoe, Heath; Lancaster, Jack; Price, Larry R; Blackmon, Karen; Berry, Kristen; Cavazos, Jose E; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas

2015-01-01

Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

The role of aqueous leaf extract of Tinospora crispa as reducing and capping agents for synthesis of gold nanoparticles

NASA Astrophysics Data System (ADS)

Apriandanu, D. O. B.; Yulizar, Y.

2017-04-01

Environmentally friendly method for green synthesis of Au nanoparticles (AuNP) using aqueous leaf extract of Tinospora crispa (TLE) was reported. TLE has the ability for reducing and capping AuNP. Identification of active compounds in aqueous leaf extract was obtained by phytochemical analysis and Fourier transform infrared spectroscopy (FTIR). The AuNP-TLE growth was characterized using UV-Vis spectrophotometer. The particle size and the distribution of AuNP were confirmed by particle size analyzer (PSA). AuNP-TLE formation was optimized by varying the extract concentration and time of the synthesis process. UV-Vis absorption spectrum of optimum AuNP formation displayed by the surface plasmon resonance at maximum wavelength of λmax 536 nm. The PSA result showed that AuNP has size distribution of 80.60 nm and stable up to 21 days. TEM images showed that the size of the AuNP is ± 25 nm.

Orbit error characteristic and distribution of TLE using CHAMP orbit data

NASA Astrophysics Data System (ADS)

Xu, Xiao-li; Xiong, Yong-qing

2018-02-01

Space object orbital covariance data is required for collision risk assessments, but publicly accessible two line element (TLE) data does not provide orbital error information. This paper compared historical TLE data and GPS precision ephemerides of CHAMP to assess TLE orbit accuracy from 2002 to 2008, inclusive. TLE error spatial variations with longitude and latitude were calculated to analyze error characteristics and distribution. The results indicate that TLE orbit data are systematically biased from the limited SGP4 model. The biases can reach the level of kilometers, and the sign and magnitude are correlate significantly with longitude.

Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus.

PubMed

He, Zhiheng; Liu, Yunhua; Liang, Deguang; Wang, Zhuo; Robertson, Erle S; Lan, Ke

2010-02-01

Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jkappa, Ap-1, C/EBP-alpha, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jkappa has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.

Tomato Lycopene Extract Prevents Lipopolysaccharide-Induced NF-κB Signaling but Worsens Dextran Sulfate Sodium-Induced Colitis in NF-κBEGFP Mice

PubMed Central

Joo, Young-Eun; Karrasch, Thomas; Mühlbauer, Marcus; Allard, Brigitte; Narula, Acharan; Herfarth, Hans H.; Jobin, Christian

2009-01-01

Background The impact of tomato lycopene extract (TLE) on intestinal inflammation is currently unknown. We investigated the effect of TLE on lipopolysaccharide (LPS)-induced innate signaling and experimental colitis. Methodology/Principal Findings Mice were fed a diet containing 0.5 and 2% TLE or isoflavone free control (AIN-76). The therapeutic efficacy of TLE diet was assessed using dextran sulfate sodium (DSS) exposed mice and IL-10−/−;NF-κBEGFP mice, representing an acute and spontaneous chronic colitis model respectively. A mini-endoscope was used to determine the extent of macroscopic mucosal lesions. Murine splenocytes and intestinal epithelial cells were used to determine the in vitro impact of TLE on LPS-induced NF-κB signaling. In vitro, TLE blocked LPS-induced IκBα degradation, RelA translocation, NF-κB transcriptional activity and MIP-2 mRNA accumulation in IEC-18 cells. Moreover, LPS-induced IL-12p40 gene expression was dose-dependently inhibited in TLE-treated splenocytes. Interestingly, DSS-induced acute colitis worsened in TLE-fed NF-κBEGFP mice compared to control diet as measured by weight loss, colonoscopic analysis and histological scores. In contrast, TLE-fed IL-10−/−;NF-κBEGFP mice displayed decreased colonic EGFP expression compared to control diet. IL-6, TNFα, and MCP-1 mRNA expression were increased in the colon of TLE-fed, DSS-exposed NF-κBEGFP mice compared to the control diet. Additionally, caspase-3 activation and TUNEL positive cells were enhanced in TLE diet-fed, DSS-exposed mice as compared to DSS control mice. Conclusions/ Significance These results indicate that TLE prevents LPS-induced proinflammatory gene expression by blocking of NF-κB signaling, but aggravates DSS-induced colitis by enhancing epithelial cell apoptosis. PMID:19234608

Ictal dystonia and secondary generalization in temporal lobe seizures: a video-EEG study.

PubMed

Popovic, Ljubica; Vojvodic, Nikola; Ristic, Aleksandar J; Bascarevic, Vladimir; Sokic, Dragoslav; Kostic, Vladimir S

2012-12-01

The aim of this study was to determine whether the occurrence of unilateral ictal limb dystonia (ID) during complex partial seizures (CPS) reduces the possibility of contralateral propagation (CP) and secondary generalization (SG) in patients with temporal lobe epilepsy (TLE). We assessed 216 seizures recorded in 33 patients with pharmacoresistant TLE. All patients underwent video-EEG telemetry prior to surgical treatment with good postoperative outcomes (Engel I). Ictal limb dystonia was observed in 16 of the 33 patients (48%) and 58 of the 216 seizures (26.8%). We found highly significant differences in the frequency of SG between seizures with ID and seizures without ID (2/58 vs. 41/158; 3.45% vs. 25.95%; p<0.001). Contralateral propagation was seen in 13 of the 57 analyzed seizures with ID compared to 85 of the 158 seizures without ID (22.8% vs. 53.8%; p<0.001). Among the CPS without SG, we found that the mean duration of seizures with ID was significantly longer than the duration of seizures without ID (81.66±40.10 vs. 68.88±25.01 s; p=0.011). Our findings that CP and SG occur less often in patients with ID, yet the duration of CPS without SG is longer in patients with ID, suggest that the basal ganglia might inhibit propagation to the contralateral hemisphere but not ictal activity within the unilateral epileptic network. Copyright © 2012 Elsevier Inc. All rights reserved.

Enhanced astroglial Ca2+ signaling increases excitatory synaptic strength in the epileptic brain.

PubMed

Álvarez-Ferradas, Carla; Morales, Juan Carlos; Wellmann, Mario; Nualart, Francisco; Roncagliolo, Manuel; Fuenzalida, Marco; Bonansco, Christian

2015-09-01

The fine-tuning of synaptic transmission by astrocyte signaling is crucial to CNS physiology. However, how exactly astroglial excitability and gliotransmission are affected in several neuropathologies, including epilepsy, remains unclear. Here, using a chronic model of temporal lobe epilepsy (TLE) in rats, we found that astrocytes from astrogliotic hippocampal slices displayed an augmented incidence of TTX-insensitive spontaneous slow Ca(2+) transients (STs), suggesting a hyperexcitable pattern of astroglial activity. As a consequence, elevated glutamate-mediated gliotransmission, observed as increased slow inward current (SICs) frequency, up-regulates the probability of neurotransmitter release in CA3-CA1 synapses. Selective blockade of spontaneous astroglial Ca(2+) elevations as well as the inhibition of purinergic P2Y1 or mGluR5 receptors relieves the abnormal enhancement of synaptic strength. Moreover, mGluR5 blockade eliminates any synaptic effects induced by P2Y1R inhibition alone, suggesting that the Pr modulation via mGluR occurs downstream of P2Y1R-mediated Ca(2+)-dependent glutamate release from astrocyte. Our findings show that elevated Ca(2+)-dependent glutamate gliotransmission from hyperexcitable astrocytes up-regulates excitatory neurotransmission in epileptic hippocampus, suggesting that gliotransmission should be considered as a novel functional key in a broad spectrum of neuropathological conditions. © 2015 Wiley Periodicals, Inc.

Verbal memory decline from hippocampal depth electrodes in temporal lobe surgery for epilepsy.

PubMed

Ljung, Hanna; Nordlund, Arto; Strandberg, Maria; Bengzon, Johan; Källén, Kristina

2017-12-01

To explore whether patients with refractory mesial temporal lobe epilepsy risk aggravated verbal memory loss from intracranial electroencephalography (EEG) recording with longitudinal hippocampal electrodes in the language-dominant hemisphere. A long-term neuropsychological follow-up (mean 61.5 months, range 22-111 months) was performed in 40 patients after ictal registration with left hippocampal depth electrodes (study group, n = 16) or no invasive EEG, only extracranial registration (reference group, n = 24). The groups were equal with respect to education, age at seizure onset, epilepsy duration, and prevalence of pharmacoresistant temporal lobe epilepsy (TLE; 75%) versus seizure freedom (25%). Retrospective neuropsychological data from preoperative surgical workup (T1) and prospective follow-up neuropsychological data (T2) were compared. A ≥1 SD intrapatient decline was considered as clinically relevant deterioration of verbal memory. Significant decline in verbal memory was seen in 56% of the patients in the study group compared to 21% in the reference group. At T1, there were no statistical between-group differences in memory performance. At T2, between-group comparison showed significantly greater verbal memory decline for the study group (Claeson Dahl Learning and Retention Test, Verbal Learning: p = 0.05; Rey Auditory Verbal Learning Test, Total Learning: p = 0.04; Claeson Dahl Learning and Retention Test, Verbal Retention: p = 0.04). An odds ratio (OR) of 7.1 (90% confidence interval [CI] 1.3-37.7) for verbal memory decline was seen if right temporal lobe resection (R TLR) had been performed between T1 and T2. The difference between groups remained unchanged when patients who had undergone R TLR were excluded from the analysis, with a remaining aggravated significant decline in verbal memory performance for the study group compared to the reference group. Our results suggest a risk of verbal memory deterioration after the use of depth electrodes along the longitudinal axis of the hippocampus. Until this issue is further investigated, caution regarding depth electrodes in the language-dominant hemisphere hippocampus seems advisable. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats.

PubMed

Drion, Cato M; Borm, Lars E; Kooijman, Lieneke; Aronica, Eleonora; Wadman, Wytse J; Hartog, Aloysius F; van Vliet, Erwin A; Gorter, Jan A

2016-05-01

Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the electrogenic post-status epilepticus (SE) rat model. Effects of mTOR inhibitor rapamycin were tested using the following three treatment protocols: (1) "stop-treatment"-post-SE treatment (6 mg/kg/day) was discontinued after 3 weeks; rats were monitored for 5 more weeks thereafter, (2) "pretreatment"-rapamycin (3 mg/kg/day) was applied during 3 days preceding SE; and (3) "chronic phase-treatment"-5 days rapamycin treatment (3 mg/kg/day) in the chronic phase. We also tested curcumin, an alternative mTOR inhibitor with antiinflammatory and antioxidant effects, using chronic phase treatment. Seizures were continuously monitored using video-electroencephalography (EEG) recordings; mossy fiber sprouting, cell death, and inflammation were studied using immunohistochemistry. Blood was withdrawn regularly to assess rapamycin and curcumin levels with high performance liquid chromatography (HPLC). Stop-treatment led to a strong reduction of seizures during the 3-week treatment and a gradual reappearance of seizures during the following 5 weeks. Three days pretreatment did not prevent seizure development, whereas 5-day rapamycin treatment in the chronic phase reduced seizure frequency. Washout of rapamycin was slow and associated with a gradual reappearance of seizures. Rapamycin treatment (both 3 and 6 mg/kg) led to body growth reduction. Curcumin treatment did not reduce seizure frequency or lead to a decrease in body weight. The present study indicates that rapamycin cannot prevent epilepsy in the electrical stimulation post-SE rat model but has seizure-suppressing properties as long as rapamycin blood levels are sufficiently high. Oral curcumin treatment had no effect on chronic seizures, possibly because it did not reach the brain at adequate levels. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

AES/GRG5: more than just a dominant-negative TLE/GRG family member.

PubMed

Beagle, Brandon; Johnson, Gail V W

2010-11-01

The human Transducin-like Enhancer of Split (TLE) and mouse homologue, Groucho gene-related protein (GRG), represent a family of conserved non-DNA binding transcriptional modulatory proteins divided into two subgroups based upon size. The long TLE/GRGs consist of four pentadomain proteins that are dedicated co-repressors for multiple transcription factors (TF). The second TLE/GRG subgroup is composed of the Amino-terminal Enhancer of Split (AES) in humans and its mouse homolog GRG5 (AES/GRG5). In contrast to the dedicated co-repressor function of long TLE/GRGs, AES/GRG5 can both positively or negatively modulate various TF as well as non-TF proteins in a long TLE/GRG-dependent or -independent manner. Therefore, AES/GRG5 is a functionally dynamic protein that is not exclusively defined by its role as a long TLE/GRG antagonist. AES/GRG5 may function in various developmental and pathological processes but the functional characteristics of endogenous AES/GRG5 in a physiologically relevant context remains to be determined. © 2010 Wiley-Liss, Inc.

Linking DMN connectivity to episodic memory capacity: What can we learn from patients with medial temporal lobe damage?

PubMed Central

McCormick, Cornelia; Protzner, Andrea B.; Barnett, Alexander J.; Cohn, Melanie; Valiante, Taufik A.; McAndrews, Mary Pat

2014-01-01

Computational models predict that focal damage to the Default Mode Network (DMN) causes widespread decreases and increases of functional DMN connectivity. How such alterations impact functioning in a specific cognitive domain such as episodic memory remains relatively unexplored. Here, we show in patients with unilateral medial temporal lobe epilepsy (mTLE) that focal structural damage leads indeed to specific patterns of DMN functional connectivity alterations, specifically decreased connectivity between both medial temporal lobes (MTLs) and the posterior part of the DMN and increased intrahemispheric anterior–posterior connectivity. Importantly, these patterns were associated with better and worse episodic memory capacity, respectively. These distinct patterns, shown here for the first time, suggest that a close dialogue between both MTLs and the posterior components of the DMN is required to fully express the extensive repertoire of episodic memory abilities. PMID:25068108

Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.

2010-04-01

Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activationmore » in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.« less

Global Interactions Analysis of Epileptic ECoG Data

NASA Astrophysics Data System (ADS)

Ortega, Guillermo J.; Sola, Rafael G.; Pastor, Jesús

2007-05-01

Localization of the epileptogenic zone is an important issue in epileptology, even though there is not a unique definition of the epileptic focus. The objective of the present study is to test ultrametric analysis to uncover cortical interactions in human epileptic data. Correlation analysis has been carried out over intraoperative Electro-Corticography (ECoG) data in 2 patients suffering from temporal lobe epilepsy (TLE). Recordings were obtained using a grid of 20 electrodes (5×4) covering the lateral temporal lobe and a strip of either 4 or 8 electrodes at the mesial temporal lobe. Ultrametric analysis was performed in the averaged final correlation matrices. By using the matrix of linear correlation coefficients and the appropriate metric distance between pairs of electrodes time series, we were able to construct Minimum Spanning Trees (MST). The topological connectivity displayed by these trees gives useful and valuable information regarding physiological and pathological information in the temporal lobe of epileptic patients.

[(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats.

PubMed

Bascuñana, Pablo; Javela, Julián; Delgado, Mercedes; Fernández de la Rosa, Rubén; Shiha, Ahmed Anis; García-García, Luis; Pozo, Miguel Ángel

2016-10-01

Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

Bio-electrochemical microelectrode arrays for glutamate and electrophysiology detection in hippocampus of temporal lobe epileptic rats.

PubMed

Li, Ziyue; Song, Yilin; Xiao, Guihua; Gao, Fei; Xu, Shengwei; Wang, Mixia; Zhang, Yu; Guo, Fengru; Liu, Jie; Xia, Yang; Cai, Xinxia

2018-06-01

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder, characterized by sudden, repeated and transient central nervous system dysfunction. For better understanding of TLE, bio-nanomodified microelectrode arrays (MEA) are designed, for the achievement of high-quality simultaneous detection of glutamate signals (Glu) and multi-channel electrophysiological signals including action potentials (spikes) and local field potentials (LFPs). The MEA was fabricated by Micro-Electro-Mechanical System fabrication technology and all recording sites were modified with platinum black nano-particles, the average impedance decreased by nearly 90 times. Additionally, glutamate oxidase was also modified for the detection of Glu. The average sensitivity of the electrode in Glu solution was 1.999 ± 0.032 × 10 -2 pA/μM·μm 2 (n = 3) and linearity was R = 0.9986, with a good selectivity of 97.82% for glutamate and effective blocking of other interferents. In the in-vivo experiments, the MEA was subjected in hippocampus to electrophysiology and Glu concentration detection. During seizures, the fire rate of spikes increases, and the interspike interval is concentrated within 30 ms. The amplitude of LFPs increases by 3 times and the power increases. The Glu level (4.22 μM, n = 4) was obviously higher than normal rats (2.24 μM, n = 4). The MEA probe provides an advanced tool for the detection of dual-mode signals in the research of neurological diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation.

PubMed

Roth, Martin; Bonev, Boyan; Lindsay, Jennefer; Lea, Robert; Panagiotaki, Niki; Houart, Corinne; Papalopulu, Nancy

2010-05-01

FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. Here, we show that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1. We show that TLE2 is co-expressed with FoxG1 in the ventral telencephalon from the early neural plate stage and functionally cooperates with FoxG1 in an ectopic neurogenesis assay. FoxG1 has two potential TLE binding sites: an N-terminal eh1 motif and a C-terminal YWPMSPF motif. Although direct binding seems to be mediated by the N-terminal motif, both motifs appear important for functional synergism. In the neurogenesis assay, mutation of either motif abolishes functional cooperation of TLE2 with FoxG1, whereas in the forebrain deletion of both motifs renders FoxG1 unable to induce the ventral telencephalic marker Nkx2.1. Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon.

FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation

PubMed Central

Roth, Martin; Bonev, Boyan; Lindsay, Jennefer; Lea, Robert; Panagiotaki, Niki; Houart, Corinne; Papalopulu, Nancy

2010-01-01

FoxG1 is a conserved transcriptional repressor that plays a key role in the specification, proliferation and differentiation of the telencephalon, and is expressed from the earliest stages of telencephalic development through to the adult. How the interaction with co-factors might influence the multiplicity and diversity of FoxG1 function is not known. Here, we show that interaction of FoxG1 with TLE2, a Xenopus tropicalis co-repressor of the Groucho/TLE family, is crucial for regulating the early activity of FoxG1. We show that TLE2 is co-expressed with FoxG1 in the ventral telencephalon from the early neural plate stage and functionally cooperates with FoxG1 in an ectopic neurogenesis assay. FoxG1 has two potential TLE binding sites: an N-terminal eh1 motif and a C-terminal YWPMSPF motif. Although direct binding seems to be mediated by the N-terminal motif, both motifs appear important for functional synergism. In the neurogenesis assay, mutation of either motif abolishes functional cooperation of TLE2 with FoxG1, whereas in the forebrain deletion of both motifs renders FoxG1 unable to induce the ventral telencephalic marker Nkx2.1. Knocking down either FoxG1 or TLE2 disrupts the development of the ventral telencephalon, supporting the idea that endogenous TLE2 and FoxG1 work together to specify the ventral telencephalon. PMID:20356955

The transcriptional co-repressor TLE3 regulates myogenic differentiation by repressing the activity of the MyoD transcription factor.

PubMed

Kokabu, Shoichiro; Nakatomi, Chihiro; Matsubara, Takuma; Ono, Yusuke; Addison, William N; Lowery, Jonathan W; Urata, Mariko; Hudnall, Aaron M; Hitomi, Suzuro; Nakatomi, Mitsushiro; Sato, Tsuyoshi; Osawa, Kenji; Yoda, Tetsuya; Rosen, Vicki; Jimi, Eijiro

2017-08-04

Satellite cells are skeletal muscle stem cells that provide myonuclei for postnatal muscle growth, maintenance, and repair/regeneration in adults. Normally, satellite cells are mitotically quiescent, but they are activated in response to muscle injury, in which case they proliferate extensively and exhibit up-regulated expression of the transcription factor MyoD, a master regulator of myogenesis. MyoD forms a heterodimer with E proteins through their basic helix-loop-helix domain, binds to E boxes in the genome and thereby activates transcription at muscle-specific promoters. The central role of MyoD in muscle differentiation has increased interest in finding potential MyoD regulators. Here we identified transducin-like enhancer of split (TLE3), one of the Groucho/TLE family members, as a regulator of MyoD function during myogenesis. TLE3 was expressed in activated and proliferative satellite cells in which increased TLE3 levels suppressed myogenic differentiation, and, conversely, reduced TLE3 levels promoted myogenesis with a concomitant increase in proliferation. We found that, via its glutamine- and serine/proline-rich domains, TLE3 interferes with MyoD function by disrupting the association between the basic helix-loop-helix domain of MyoD and E proteins. Our findings indicate that TLE3 participates in skeletal muscle homeostasis by dampening satellite cell differentiation via repression of MyoD transcriptional activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural correlates of impaired working memory in hippocampal sclerosis.

PubMed

Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S

2013-07-01

Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

PubMed Central

Polli, Roberson S.; Malheiros, Jackeline M.; dos Santos, Renan; Hamani, Clement; Longo, Beatriz M.; Tannús, Alberto; Mello, Luiz E.; Covolan, Luciene

2014-01-01

Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that these are not significantly correlated to the frequency of SRS. PMID:25071699

TLE uncertainty estimation using robust weighted differencing

NASA Astrophysics Data System (ADS)

Geul, Jacco; Mooij, Erwin; Noomen, Ron

2017-05-01

Accurate knowledge of satellite orbit errors is essential for many types of analyses. Unfortunately, for two-line elements (TLEs) this is not available. This paper presents a weighted differencing method using robust least-squares regression for estimating many important error characteristics. The method is applied to both classic and enhanced TLEs, compared to previous implementations, and validated using Global Positioning System (GPS) solutions for the GOCE satellite in Low-Earth Orbit (LEO), prior to its re-entry. The method is found to be more accurate than previous TLE differencing efforts in estimating initial uncertainty, as well as error growth. The method also proves more reliable and requires no data filtering (such as outlier removal). Sensitivity analysis shows a strong relationship between argument of latitude and covariance (standard deviations and correlations), which the method is able to approximate. Overall, the method proves accurate, computationally fast, and robust, and is applicable to any object in the satellite catalogue (SATCAT).

Psychiatric consequences of temporal lobectomy for intractable seizures: a 20-30-year follow-up of 14 cases.

PubMed

Stevens, J R

1990-08-01

Between 1958 and 1968, 14 patients from the epilepsy clinic at the University of Oregon Hospitals and Clinics with a diagnosis of temporal lobe epilepsy (TLE) had a temporal lobectomy for medically intractable seizures. Nine of the 14 patients operated on remained seizure-free over the 20-30-year period of follow-up. Between 6 months and one year following temporal lobectomy, two women, previously healthy from a psychiatric standpoint, developed psychoses, and the previous psychiatric problems of four other patients worsened. Two patients, one with incapacitating paranoid personality disorder and the other with explosive rage attacks preoperatively, had marked improvement in their psychiatric status following temporal lobectomy. The remaining six patients, all psychiatrically healthy prior to surgery, have had no change in psychiatric status following surgery. Development of psychosis or deterioration in psychiatric status after surgery was more common in patients with later age of onset, unreality or déjà vu rather than epigastric aura, pre-operative evidence of bilateral brain damage, and persistence of EEG or clinical seizure activity. Development of a chronic psychosis in psychiatrically healthy individuals many months after temporal lobectomy, even when seizures are arrested or ameliorated, suggests that anomalous synaptic regeneration may follow the surgery in these cases. Careful analysis of histories and outcomes may contribute to better understanding of the pathophysiology and anatomical substrates of psychoses.

Experimental observation of ion-cyclotron turbulence in the presence of transverse-velocity shear. Ph.D. Thesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amatucci, W.E.

1994-01-01

This laboratory investigation documents the influence of transverse, localized, dc electric fields (TLE) on the excitation of ion-cyclotron waves driven by magnetic field-aligned current (FAC) in a Q-machine plasma device. A segmented disk electrode, located on axis at the end of the plasma column, is used to independently control TLE and FAC in the plasma (potassium plasma, n approximately equals 10(exp 9) cm(exp {minus}3), rho(i) approximately equals 0.2 cm, T(e) = T(i) approximately equals 0.2 eV). Ion-cyclotron waves have been characterized in both the weak-TLE and large-FAC regime and the strong-TLE and small-FAC regime. The existence of a new categorymore » of oscillation identified as the inhomogeneous energy-density driven (IEDD) instability is verified based on the properties of the waves in the latter regime. In the weak-TLE regime, current-driven electrostatic ion-cyclotron (CDEIC) waves with features in qualitative agreement with previous laboratory results have been observed at sufficiently large FAC. These waves have a frequency spectrum with a single narrow spectral feature located slightly above the ion-cyclotron frequency (omega approximately equals 1.2 Omega(i)). The waves are standing in the radial direction with peak oscillation amplitude located in the center of the FAC channel and are azimuthally symmetric (m = 0). Small magnitude TLE were found to have negligible effect on the characteristics of the waves. In the strong-TLE regime, a decrease in the threshold FAC level is observed. This transition in the instability threshold is accompanied by changes in the frequency spectra, propagation characteristics, and mode amplitude profiles. In the presence of strong-TLE, the ion-cyclotron waves propagate azimuthally in the E x B direction with k(theta) rho(i) = 0.4 and m = 1. The frequency spectrum becomes broadband and spiky, and shifts with the applied TLE strength.« less

Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takamiya, Masanori; Nakamura, Mitsuhiro, E-mail: m-nkmr@kuhp.kyoto-u.ac.jp; Akimoto, Mami

Purpose: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). Methods: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as themore » target (P{sub t}), and those markers with a 3D |TMD{sub n}| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (P{sub e}) was calculated from a localization point consisting of one to three markers except P{sub t}. Respiratory motion for P{sub t} and P{sub e} was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between P{sub t} and P{sub e} during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. Results: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker’s motion near the lung tumor. MRA showed that |aRM| in the left–right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left–right direction. The TLE calculated from the MRA ({sup MRA}TLE) increased as |TMD| and |aRM| increased and adversely decreased with each increment of n. The median 3D {sup MRA}TLE was 2.0 mm (range, 0.6–4.3 mm) for n = 1, 1.8 mm (range, 0.4–4.0 mm) for n = 2, and 1.6 mm (range, 0.3–3.7 mm) for n = 3. Although statistical significance between n = 1 and n = 3 was observed in all directions, the absolute average difference and the standard deviation of the {sup MRA}TLE between n = 1 and n = 3 were 0.5 and 0.2 mm, respectively. Conclusions: A large |TMD| and |aRM| increased the differences in TLE between each n; however, the difference in 3D {sup MRA}TLEs was, at most, 0.6 mm. Thus, the authors conclude that it is acceptable to continue fiducial marker-based radiotherapy as long as |TMD| is maintained at ≤58.7 mm for a 3D |aRM|  ≥  10 mm.« less

Effect of Naringenin (A naturally occurring flavanone) Against Pilocarpine-induced Status Epilepticus and Oxidative Stress in Mice

PubMed Central

Shakeel, Sheeba; Rehman, Muneeb U.; Tabassum, Nahida; Amin, Umar; Mir, Manzoor ur Rahman

2017-01-01

Background: Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. It is a very common disease in which approximately 30% of patients do not respond favourably to treatment with anticonvulsants. Oxidative stress is associated with neuronal damage arising from epileptic seizures. The present study investigated the effects of naringenin in pilocarpine-induced epilepsy in mice. Naringenin, one of the most frequently occurring flavanone in citrus fruits, was evaluated for its shielding effect against the pilocarpine induced behavioural, oxidative and histopathological alterations in rodent model of epilepsy. Methodology: Epilepsy was induced by giving pilocarpine (300mg/kg) and sodium valproate (300mg/kg) was given as standard anti-epileptic drug Pilocarpine was administered (300 mg /kg body weight) intraperitoneally to the mice on 15th day while naringenin was administered orally (20 and 40 mg/kg body weight) for 15 days prior to administration of pilocarpine. Results: The intraperitoneal administration of pilocarpine enhanced lipid peroxidation, caused reduction in antioxidant enzymes, viz., catalase, superoxide dismutase and glutathione reductase. Treatment of mice orally with naringenin (20 mg/kg body weight and 40 mg/kg body weight) resulted in a significant decrease in lipid peroxidation. There was significant recovery of glutathione content and all the antioxidant enzymes studied. Also in case of behavioural parameters studied, naringenin showed decrease in seizure severity. All these changes were supported by histological observations, which revealed excellent improvement in neuronal damage. Conclusion: The higher dose of naringenin was more potent in our study and was comparable to the standard drug (sodium valproate) in effectiveness. SUMMARY Naringenin ameliorated the development of ROS formation in hippocamus.Naringenin helped in recovery of antioxidant enzymes.Naringenin decreased seizure severity.Naringenin treatment reduced lipid peroxidation. Abbreviations used: 6-OHDA: 6-hydroxydopamine, AED: Anti epileptic drugs, AIDS: Acquired immune deficiency syndrome, ANOVA: Analysis of variance, ATP: Adenosine triphosphate, CA: Cornu ammonis, CAT: Catalase, DG: Dentate gyrus, EDTA: Ethylenediamine tetra acetic acid, GR: Glutathione reductase, GSH: Glutathione reduced, HCl: Hydrochloric acid, IL-1β: Interleukin 1 beta, LPO: Lipid peroxidation, MDA: Malondialdehyde, NADPH: Nicotinamide adenine dinucleotide phosphate, PMS: post mitochondrial supernatant, SE: Status epilepticus, SEM: Standard error of the mean, SOD Superoxide dismutase, TBA: Thiobarbituric acid, TBARS: Thiobarbituric acid reactive substance, TLE: Temporal lobe epilepsy, TNF-α: Tumor necrosis factor alpha PMID:28479741

Requirement of longitudinal synchrony of epileptiform discharges in the hippocampus for seizure generation: a pilot study.

PubMed

Umeoka, Shuichi C; Lüders, Hans O; Turnbull, John P; Koubeissi, Mohamad Z; Maciunas, Robert J

2012-03-01

The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT). In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3). Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdala on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure--namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years. These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.

Transvenous Lead Extraction in Adults With Congenital Heart Disease: Insights From a 20-Year Single-Center Experience.

PubMed

Gourraud, Jean-Baptiste; Chaix, Marie-A; Shohoudi, Azadeh; Pagé, Pierre; Dubuc, Marc; Thibault, Bernard; Poirier, Nancy C; Dore, Annie; Marcotte, François; Mongeon, François-Pierre; Asgar, Anita W; Ibrahim, Réda; Khairy, Paul; Mondésert, Blandine

2018-02-01

Safety and feasibility data on transvenous lead extraction (TLE) in the challenging population of adults with congenital heart disease (A-CHD) are limited. Herein, we report the results of TLE in A-CHD during a 20-year period. All consecutive TLE procedures in A-CHD were included in a monocentric prospective registry from 1996. A total of 121 leads were extracted in 49 A-CHD (median age, 38 years; 51% men) during 71 TLE procedures. Twenty-four (49%) patients had transposition of the great arteries. Main indications for extraction were infection in 34 (48%) and lead failure in 22 (31%). A laser sheath was required for 56 (46%) leads and a femoral approach for 10 (8%). Complete TLE was achieved for 111 leads (92%). In multivariable analysis, lead duration (odds ratio, 1.02; 95% confidence interval, 1.00-1.04; P <0.01) and number of previous cardiac surgeries (odds ratio, 2.65; 95% confidence interval, 1.52-4.67; P <0.01) were predictive of TLE failure. No perioperative death or pericardial effusion was observed. Subpulmonary atrioventricular valve regurgitation increased in 8 patients (5 with transposition of the great arteries) and was independently associated with an implantable cardioverter defibrillator lead (odds ratio, 9.69; 95% confidence interval, 1.31-71.64; P =0.03) and valvular vegetation (odds ratio, 7.29; 95% confidence interval, 1.32-40.51; P =0.02). After a median of 54 (19-134) months of follow-up after the first TLE, 3 deaths occurred independently from lead management. Despite complex anatomic issues, TLE can be achieved successfully in most A-CHD using advanced extraction techniques. Subpulmonary atrioventricular valve regurgitation is a prevalent complication, particularly in patients with transposition of the great arteries. © 2018 American Heart Association, Inc.

Surgery in temporal lobe epilepsy patients without cranial MRI lateralization.

PubMed

Gomceli, Y B; Erdem, A; Bilir, E; Kutlu, G; Kurt, S; Erden, E; Karatas, A; Erbas, C; Serdaroglu, A

2006-03-01

High resolution MRI is very important in the evaluations of patients with intractable temporal lobe epilepsy in preoperative investigations. Morphologic abnormalities on cranial MRI usually indicate the epileptogenic focus. Intractable TLE patients who have normal cranial MRI or bilateral hippocampal atrophy may have a chance for surgery if a certain epileptogenic focus is determined. We evaluated the patients who were monitorized in Gazi University Medical Faculty Epilepsy Center from October 1997 to April 2004. Seventy three patients, who had a temporal epileptogenic focus, underwent anterior temporal lobectomy at Ankara University Medical Faculty Department of Neurosurgery. Twelve of them (16, 4%), did not have any localizing structural lesion on cranial MRI. Of the 12 patients examined 6 had normal findings and 6 had bilateral hippocampal atrophy. Of these 12 patients, 6 (50%) were women and 6 (50%) were men. The ages of patients ranged from 7 to 37 (mean: 24.5). Preoperatively long-term scalp video-EEG monitoring, cranial MRI, neuropsychological tests, and Wada test were applied in all patients. Five patients, whose investigations resulted in conflicting data, underwent invasive monitoring by the use of subdural strips. The seizure outcome of patients were classified according to Engel with postsurgical follow-up ranging from 11 to 52 (median: 35.7) months. Nine patients (75%) were classified into Engel's Class I and the other 3 patients (25%) were placed into Engel's Class II. One patient who was classified into Engel's Class II had additional psychiatric problems. The other patient had two different epileptogenic foci independent from each other in her ictal EEG. One of them localized in the right anterior temporal area, the other was in the right frontal lobe. She was classified in Engel's Class II and had no seizure originating from temporal epileptic focus, but few seizures originating from the frontal region continued after the surgery. In conclusion, surgery was successful in all 12 patients. We think that patients with no MRI lateralizing or localizing lesion should undergo epilepsy surgery after detailed presurgical evaluations, including invasive monitoring.

Activation of AKT/GSK3β pathway by TDZD-8 attenuates kainic acid induced neurodegeneration but not seizures in mice.

PubMed

Bhowmik, Malay; Khanam, Razia; Saini, Neeru; Vohora, Divya

2015-01-01

Activation of glycogen synthase kinase3β (GSK3β), an enzyme that regulates a multitude of cellular signaling pathways, is implicated in neurodegenerative processes observed in an array of CNS diseases. We examined the hypothesis that the pathological changes in an acute kainic acid (KA) induced excitotoxicity model, relevant to human temporal lobe epilepsy (TLE), could be sensitive to inhibition of GSK3β by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) treatment in Swiss albino mice. Immediate seizure responses due to KA were recorded. Neurodegenerative and morphogenic changes were examined by western blot analysis and light microscopy, respectively, 48 h after KA administration. Although tonic-clonic seizure episodes evoked by KA were unaffected, TDZD-8 pretreatment decreased KA mediated elevation in caspase-3 cleavage as well as increased Bcl2 and phospho-GSK3β (Ser9; pGSK3β(Ser9)) expression. Likewise, microscopic examination also revealed that pretreatment with TDZD-8 attenuated cell damage elicited by KA in the CA1, CA3 and DG regions. In all the above parameters, the combined effect of a sub-effective dose of sodium valproate (SVP) with TDZD-8 was higher than that of solitary TDZD-8 treatment. The findings suggest that activated GSK3β orchestrated neurodegenerative alterations following KA treatment and its inhibition by TDZD-8 affords a distinct neuroprotective profile by activating Akt/GSK3β pathway which might act upstream of Bax/Bcl2 and caspase-3 pathways. Compounds targeting GSK3β activity might represent a novel therapeutic option for exploration as an adjunct to conventional anti-epileptic drugs in preventing neurodegenerative processes in TLE. Copyright © 2014 Elsevier Inc. All rights reserved.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during rey auditory verbal learning test.

PubMed

Babiloni, Claudio; Vecchio, Fabrizio; Mirabella, Giovanni; Buttiglione, Maura; Sebastiano, Fabio; Picardi, Angelo; Di Gennaro, Giancarlo; Quarato, Pier P; Grammaldo, Liliana G; Buffo, Paola; Esposito, Vincenzo; Manfredi, Mario; Cantore, Giampaolo; Eusebi, Fabrizio

2009-07-01

It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten ["subsequent memory effect" (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug-resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3-8 Hz) rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital-temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40-45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug-resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal-occipital neocortex. Copyright 2009 Wiley-Liss, Inc

Synchronous high-frequency oscillations in inhibitory-dominant network motifs consisting of three dentate gyrus-CA3 systems

NASA Astrophysics Data System (ADS)

Zhang, Liyuan; Fan, Denggui; Wang, Qingyun

2018-06-01

Studies on the structural-functional connectomes of the human brain have demonstrated the existence of synchronous firings in a specific brain network motif. In particular, synchronization of high-frequency oscillations (HFOs) has been observed in the experimental data sets of temporal lobe epilepsy (TLE). In addition, both clinical and experimental evidences have accumulated to demonstrate the effect of electrical stimulation on TLE, which, however, remains largely unexplored. In this work, we first employ our previously proposed dentate gyrus (DG)-CA3 network model to investigate the influence of an external electrical stimulus on the HFO transitions. The results indicate that the reinforcing stimulus can induce the HFO transitions of the DG-CA3 system from the gamma band to the fast ripples band. Along with that, the consistent oscillations of neurons within DG-CA3 can also be enhanced with the increasing of stimulus. Then, we expand into a simple motif of three coupled DG-CA3 systems in both the feedforward inhibition and feedback inhibition connections, to investigate the synchronous evolutions of HFOs by regulating both the stimulation strength and inhibitory function. It is shown that the comprehensive effects, which lead to band transition, are independent of the motif configurations. The enhanced external electrical stimulus weakens the synchronism and correlation of connected motifs. In contrast, we demonstrate that the increased inhibitory coupling could facilitate correlation to some extent. Overall, our work highlights the possible origin of synchronous HFOs of hippocampal motifs governed by external inputs and inhibitory connection, which might contribute to a better understanding of the interplay between synchronization dynamics and epileptic structure in the human brain.

Parvalbumin interneurons and calretinin fibers arising from the thalamic nucleus reuniens degenerate in the subiculum after kainic acid-induced seizures

PubMed Central

Drexel, M.; Preidt, A.P.; Kirchmair, E.; Sperk, G.

2011-01-01

The subiculum is the major output area of the hippocampus. It is closely interconnected with the entorhinal cortex and other parahippocampal areas. In animal models of temporal lobe epilepsy (TLE) and in TLE patients it exerts increased network excitability and may crucially contribute to the propagation of limbic seizures. Using immunohistochemistry and in situ-hybridization we now investigated neuropathological changes affecting parvalbumin and calretinin containing neurons in the subiculum and other parahippocampal areas after kainic acid-induced status epilepticus. We observed prominent losses in parvalbumin containing interneurons in the subiculum and entorhinal cortex, and in the principal cell layers of the pre- and parasubiculum. Degeneration of parvalbumin-positive neurons was associated with significant precipitation of parvalbumin-immunoreactive debris 24 h after kainic acid injection. In the subiculum the superficial portion of the pyramidal cell layer was more severely affected than its deep part. In the entorhinal cortex, the deep layers were more severely affected than the superficial ones. The decrease in number of parvalbumin-positive neurons in the subiculum and entorhinal cortex correlated with the number of spontaneous seizures subsequently experienced by the rats. The loss of parvalbumin neurons thus may contribute to the development of spontaneous seizures. On the other hand, surviving parvalbumin neurons revealed markedly increased expression of parvalbumin mRNA notably in the pyramidal cell layer of the subiculum and in all layers of the entorhinal cortex. This indicates increased activity of these neurons aiming to compensate for the partial loss of this functionally important neuron population. Furthermore, calretinin-positive fibers terminating in the molecular layer of the subiculum, in sector CA1 of the hippocampus proper and in the entorhinal cortex degenerated together with their presumed perikarya in the thalamic nucleus reuniens. In addition, a significant loss of calretinin containing interneurons was observed in the subiculum. Notably, the loss in parvalbumin positive neurons in the subiculum equaled that in human TLE. It may result in marked impairment of feed-forward inhibition of the temporo-ammonic pathway and may significantly contribute to epileptogenesis. Similarly, the loss of calretinin-positive fiber tracts originating from the nucleus reuniens thalami significantly contributes to the rearrangement of neuronal circuitries in the subiculum and entorhinal cortex during epileptogenesis. PMID:21616128

Combined quantification of faecal sterols, stanols, stanones and bile acids in soils and terrestrial sediments by gas chromatography-mass spectrometry.

PubMed

Birk, Jago Jonathan; Dippold, Michaela; Wiesenberg, Guido L B; Glaser, Bruno

2012-06-15

Faeces incorporation can alter the concentration patterns of stanols, stanones, Δ(5)-sterols and bile acids in soils and terrestrial sediments. A joint quantification of these substances would give robust and specific information about the faecal input. Therefore, a method was developed for their purification and determination via gas chromatography-mass spectrometry (GC-MS) based on a total lipid extract (TLE) of soils and terrestrial sediments. Stanols, stanones, Δ(5)-steroles and bile acids were extracted by a single Soxhlet extraction yielding a TLE. The TLE was saponified with KOH in methanol. Sequential liquid-liquid extraction was applied to recover the biomarkers from the saponified extract and to separate the bile acids from the neutral stanoles, stanones and Δ(5)-steroles. The neutral fraction was directly purified using solid phase extraction (SPE) columns packed with 5% deactivated silica gel. The bile acids were methylated in dry HCl in methanol and purified on SPE columns packed with activated silica gel. A mixture of hexamethyldisilazane (HMDS), trimethylchlorosilane (TMCS) and pyridine was used to silylate the hydroxyl groups of the stanols and Δ(5)-sterols avoiding a silylation of the keto groups of the stanones in their enol-form. Silylation of the bile acids was carried out with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) containing N-trimethylsilylimidazole (TSIM). TLEs from a set of soils with different physico-chemical properties were used for method evaluation and for comparison of amounts of faecal biomarkers analysed with saponification and without saponification of the TLE. Therefore, a Regosol, a Podzol and a Ferralsol were sampled. To proof the applicability of the method for faecal biomarker analyses in archaeological soils and sediments, additional samples were taken from pre-Columbian Anthrosols in Amazonia and an Anthrosol from a site in central Europe settled since the Neolithic. The comparison of the amounts of steroids in combination with and without saponification of the TLE showed that high amounts of faecal biomarkers occur bound to other lipids and were liberated by saponification. The method was evaluated by standard addition. The standard contained 5β-stanols, 5β-stanones and their 5α-isomers together with Δ(5)-sterols and bile acids (19 substances). The standard addition revealed mean recoveries of individual substances ≥85%. The recoveries of biomarkers within each biomarker group did not differ significantly. Precisions were ≤0.22 (RSD) and quantification limits were between 1.3 and 10 ng g(-1) soil. These data showed that the method can be applied for quantification of trace amounts of faecal steroids and for the analyses of steroid patterns to detect enhanced faeces deposition in soils and sediments. Copyright © 2012 Elsevier B.V. All rights reserved.

The GABAB receptor agonist, baclofen, contributes to three distinct varieties of amnesia in the human brain - A detailed case report.

PubMed

Zeman, Adam; Hoefeijzers, Serge; Milton, Fraser; Dewar, Michaela; Carr, Melanie; Streatfield, Claire

2016-01-01

We describe a patient in whom long-term, therapeutic infusion of the selective gamma-amino-butyric acid type B (GABAB) receptor agonist, baclofen, into the cerebrospinal fluid (CSF) gave rise to three distinct varieties of memory impairment: i) repeated, short periods of severe global amnesia, ii) accelerated long-term forgetting (ALF), evident over intervals of days and iii) a loss of established autobiographical memories. This pattern of impairment has been reported in patients with temporal lobe epilepsy (TLE), in particular the subtype of Transient Epileptic Amnesia (TEA). The amnesic episodes and accelerated forgetting remitted on withdrawal of baclofen, while the autobiographical amnesia (AbA) persisted. This exceptional case highlights the occurrence of 'non-standard' forms of human amnesia, reflecting the biological complexity of memory processes. It suggests a role for GABAB signalling in the modulation of human memory over multiple time-scales and hints at its involvement in 'epileptic amnesia'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automated Epileptic Seizure Detection Based on Wearable ECG and PPG in a Hospital Environment

PubMed Central

De Cooman, Thomas; Gu, Ying; Cleeren, Evy; Claes, Kasper; Van Paesschen, Wim; Van Huffel, Sabine; Hunyadi, Borbála

2017-01-01

Electrocardiography has added value to automatically detect seizures in temporal lobe epilepsy (TLE) patients. The wired hospital system is not suited for a long-term seizure detection system at home. To address this need, the performance of two wearable devices, based on electrocardiography (ECG) and photoplethysmography (PPG), are compared with hospital ECG using an existing seizure detection algorithm. This algorithm classifies the seizures on the basis of heart rate features, extracted from the heart rate increase. The algorithm was applied to recordings of 11 patients in a hospital setting with 701 h capturing 47 (fronto-)temporal lobe seizures. The sensitivities of the hospital system, the wearable ECG device and the wearable PPG device were respectively 57%, 70% and 32%, with corresponding false alarms per hour of 1.92, 2.11 and 1.80. Whereas seizure detection performance using the wrist-worn PPG device was considerably lower, the performance using the wearable ECG is proven to be similar to that of the hospital ECG. PMID:29027928

Automated Epileptic Seizure Detection Based on Wearable ECG and PPG in a Hospital Environment.

PubMed

Vandecasteele, Kaat; De Cooman, Thomas; Gu, Ying; Cleeren, Evy; Claes, Kasper; Paesschen, Wim Van; Huffel, Sabine Van; Hunyadi, Borbála

2017-10-13

Electrocardiography has added value to automatically detect seizures in temporal lobe epilepsy (TLE) patients. The wired hospital system is not suited for a long-term seizure detection system at home. To address this need, the performance of two wearable devices, based on electrocardiography (ECG) and photoplethysmography (PPG), are compared with hospital ECG using an existing seizure detection algorithm. This algorithm classifies the seizures on the basis of heart rate features, extracted from the heart rate increase. The algorithm was applied to recordings of 11 patients in a hospital setting with 701 h capturing 47 (fronto-)temporal lobe seizures. The sensitivities of the hospital system, the wearable ECG device and the wearable PPG device were respectively 57%, 70% and 32%, with corresponding false alarms per hour of 1.92, 2.11 and 1.80. Whereas seizure detection performance using the wrist-worn PPG device was considerably lower, the performance using the wearable ECG is proven to be similar to that of the hospital ECG.

Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors and outcome

PubMed Central

Clusmann, H; Kral, T; Fackeldey, E; Blumcke, I; Helmstaedter, C; von Oertzen, J; Urbach, H; Schramm, J

2004-01-01

Objectives: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). Methods: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990–2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. Results: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors "seizure onset after 10 years of age", "presence of complex partial seizures", "absence of a neurological deficit", and a "correlating neuropsychological deficit" as predictive for satisfactory seizure control. Conclusions: "Preoperative tailoring" resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE. PMID:15489392

Lead dependent tricuspid dysfunction: Analysis of the mechanism and management in patients referred for transvenous lead extraction.

PubMed

Polewczyk, Anna; Kutarski, Andrzej; Tomaszewski, Andrzej; Brzozowski, Wojciech; Czajkowski, Marek; Polewczyk, Maciej; Janion, Marianna

2013-01-01

Lead-dependent tricuspid dysfunction (LDTD) is one of important complications in patients with cardiac implantable electronic devices. However, this phenomenon is probably underestimated because of an improper interpretation of its clinical symptoms. The aim of this study was to identify LDTD mechanisms and management in patients referred for transvenous lead extraction (TLE) due to lead-dependent complications. Data of 940 patients undergoing TLE in a single center from 2009 to 2011 were assessed and 24 patients with LDTD were identifi ed. The general indications for TLE, pacing system types and lead dwell time in both study groups were comparatively analyzed. The radiological and clinical effi cacy of TLE procedure was also assessed in both groups with precision estimation of clinical status patients with LDTD (before and after TLE). Additionally, mechanisms, concomitant lead-dependent complications and degree (severity) of LDTD before and after the procedure were evaluated. Telephone follow-up of LDTD patients was performed at the mean time 1.5 years after TLE/replacement procedure. The main indications for TLE in both groups were similar (apart from isolated LDTD in 45.83% patients from group I). Patients with LDTD had more complex pacing systems with more leads (2.04 in the LDTD group vs. 1.69 in the control group; p = 0.04). There were more unnecessary loops of lead in LDTD patients than in the control group (41.7% vs. 5.24%; p = 0.001). There were no signifi cant differences in average time from implantation to extraction and the number of preceding procedures. Signifi cant tricuspid regurgitation (TR-grade III-IV) was found in 96% of LDTD patients, whereas stenosis with regurgitation in 4%. The 10% frequency of severe TR (not lead dependent) in the control group patients was observed. The main mechanism of LDTD was abnormal leafl et coaptation caused by: loop of the lead (42%), septal leafl et pulled toward the interventricular septum (37%) or too intensive lead impingement of the leafl ets (21%). LDTD patients were treated with TLE and reimplantation of the lead to the right ventricle (87.5%) or to the cardiac vein (4.2%), or surgery procedure with epicardial lead placement following ineffective TLE (8.3%). The radiological and clinical effi cacy of TLE procedure was very high and comparable between the groups I and II (91.7% vs. 94.2%; p = 0.6 and 100% vs. 98.4%; p = 0.46, respectively). Repeated echocardiography showed reduced severity of tricuspid valve dysfunction in 62.5% of LDTD patients. The follow- -up interview confi rmed clinical improvement in 75% of patients (further improvement after cardiosurgery in 2 patients was observed). LDTD is a diagnostic and therapeutic challenge. The main reason for LDTD was abnormal leafl et coaptation caused by lead loop presence, or propping, or impingement the leafl ets by the lead. Probably, TLE with lead reimplantation is a safe and effective option in LDTD management. An alternative option is TLE with omitted tricuspid valve reimplantation. Cardiac surgery with epicardial lead placement should be reserved for patients with ineffective previous procedures.

Is 'burned-out hippocampus' syndrome a distinct electro-clinical variant of MTLE-HS syndrome?

PubMed

Nair, Pradeep P; Menon, Ramshekhar N; Radhakrishnan, Ashalatha; Cherian, Ajit; Abraham, Mathew; Vilanilam, George; Kesavadas, C; Thomas, Bejoy; Alexander, Aley; Thomas, Sanjeev V

2017-04-01

To study the clinical, electrophysiological and imaging characteristics of patients with unilateral mesial temporal lobe epilepsy (MTLE) with contralateral ictal onset on scalp EEG, viz. 'burned-out hippocampus' syndrome (MTLE-BHS). MTLE-BHS was defined as TLE with unilateral hippocampal sclerosis (HS) without any dual pathology on MRI and contralateral ictal onset on scalp EEG, unlike in classical hippocampal sclerosis (HS). Consecutive "MTLE-BHS" patients evaluated at our Centre for Comprehensive Epilepsy Care from January 2005 to July 2014 were studied. Twenty-five cases of classic MTLE-HS operated during the same period were also analyzed for comparison. Seventeen patients were diagnosed to have MTLE-BHS. Mean age of seizure onset was 9.5±7.7years and the mean duration of epilepsy was18.2±7.3years. Epigastric aura was more common in MTLE-HS and fear, secondary generalized seizures and temporal polar changes on MRI were more prevalent in the MTLE-BHS subgroup. In the latter group, five (29%) exhibited seizure semiology and 2 (12%) had interictal discharges discordant to the side of MTS. Eight (47%) patients in the MTLE-BHS sub-group had normal medial temporal volume on Scheltens scale. Eight patients among MTLE-BHS underwent surgery (4 following intracranial monitoring that localized to the side of HS) with Engel class I outcome at 1year follow-up in 6 and Engel class II outcome in 2. Attenuation of ipsilateral fast ictal rhythms on scalp EEG as well as neocortical changes are likely to be deterministic factors for MTLE-BHS as opposed to the severity of hippocampal atrophy. Considering good post-operative outcomes, intracranial monitoring for surgical selection is not mandatory in MTLE-BHS despite discordant semiology and ictal onset, in the presence of inter-ictal, functional imaging and neuropsychology data concordant to the side of HS. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and Phenomenology of the FEBSTAT Study

PubMed Central

Hesdorffer, Dale C; Shinnar, Shlomo; Lewis, Darrell V; Moshé, Solomon L; Nordli, Douglas R; Pellock, John M; MacFall, James; Shinnar, Ruth C; Masur, David; Frank, L Matthew; Epstein, Leon G; Litherland, Claire; Seinfeld, Syndi; Bello, Jacqueline A; Chan, Stephen; Bagiella, Emilia; Sun, Shumei

2012-01-01

Purpose Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hipppocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology. Methods The “Consequences of Prolonged Febrile Seizures in Childhood” (FEBSTAT) study is a prospective, multicenter study. Enrolled are children, aged 1 month to 6 years, presenting with a febrile seizure lasting 30 minutes or more based upon ambulance, emergency department, and hospital records, and parental interview. At baseline, procedures included an MRI and EEG done within 72 hours of FSE, and a detailed history and neurological examination. Baseline development and behavior are assessed at one month. The baseline assessment is repeated, with age- appropriate developmental testing at one and five years after enrollment as well as at the development of epilepsy and one year after that. Telephone calls every three months document further seizures. Two other groups of children are included: a ‘control’ group consisting of children with a first febrile seizure ascertained at Columbia University and with almost identical baseline and one year follow-up examinations and a pilot cohort of FSE from Duke University. Key findings The FEBSTAT cohort consists of 199 children with a median age at baseline of 16.0 months (Interquartile range (IQR)=12.0–24.0) and a median duration of FSE of 70.0 minutes (IQR=47.0–110.0). Seizures were continuous in 57.3% and behaviorally intermittent (without recovery in between) in 31.2%; most were partial (4;2.0%) or secondary generalized (65.8%), and almost all (98.0%) culminated in a generalized tonic clonic seizure. Of the 199 children, 86.4% had normal development and 20% had prior febrile seizures. In one third of cases, FSE was unrecognized in the emergency department. The Duke existing cohort consists of 23 children with a median age of FSE onset of 18.0 months (IQR 14.0–28.0) and median duration of FSE of 90.0 minutes (IQR 50.0–170.0). The Columbia control cohort consists of 159 children with a first febrile seizure who received almost the same work-up as the FEBSTAT cohort at baseline and at one-year. They were followed by telephone every 4 months for a median of 42 months. Among the control cohort, 64.2% had a first simple FS, 26.4% had a first complex FS that was not FSE, and 9.4% had FSE. Among the 15 with FSE, the median age at onset was 14.0 months (IQR 12.0–20.0) and the median duration of FSE was 43.0 minutes (IQR 35.0–75.0). Significance The FEBSTAT study presents an opportunity to prospectively study the relationship between FSE and acute hippocampal damage, the development of MTS, epilepsy (particularly TLE), and impaired hippocampal function in a large cohort. It is hoped that this study may illuminate a major mystery in clinical epilepsy today, and permit the development of interventions designed to prevent the sequelae of FSE. PMID:22742587

Characterising the three-dimensional ozone distribution of a tidally locked Earth-like planet

NASA Astrophysics Data System (ADS)

Proedrou, Elisavet; Hocke, Klemens

2016-06-01

We simulate the 3D ozone distribution of a tidally locked Earth-like exoplanet using the high-resolution, 3D chemistry-climate model CESM1(WACCM) and study how the ozone layer of a tidally locked Earth (TLE) (Ω _{TLE}= 1/365 days) differs from that of our present-day Earth (PDE) (Ω _{PDE}= 1/1 day). The middle atmosphere reaches a steady state asymptotically within the first 80 days of the simulation. An upwelling, centred on the subsolar point, is present on the day side while a downwelling, centred on the antisolar point, is present on the night side. In the mesosphere, we find similar global ozone distributions for the TLE and the PDE, with decreased ozone on the day side and enhanced ozone on the night side. In the lower mesosphere, a jet stream transitions into a large-scale vortex around a low-pressure system, located at low latitudes of the TLE night side. In the middle stratosphere, the concentration of odd oxygen is approximately equal to that of the ozone [({O}x) ≈ ({O}3)]. At these altitudes, the lifetime of odd oxygen is ˜16 h and the transport processes significantly contribute to the global distribution of stratospheric ozone. Compared to the PDE, where the strong Coriolis force acts as a mixing barrier between low and high latitudes, the transport processes of the TLE are governed by jet streams variable in the zonal and meridional directions. In the middle stratosphere of the TLE, we find high ozone values on the day side, due to the increased production of atomic oxygen on the day side, where it immediately recombines with molecular oxygen to form ozone. In contrast, the ozone is depleted on the night side, due to changes in the solar radiation distribution and the presence of a downwelling. As a result of the reduced Coriolis force, the tropical and extratropical air masses are well mixed and the global temperature distribution of the TLE stratosphere has smaller horizontal gradients than the PDE. Compared to the PDE, the total ozone column global mean is reduced by ˜19.3 %. The day side and the night side total ozone column means are reduced by 23.21 and 15.52 %, respectively. Finally, we present the total ozone column (TOC) maps as viewed by a remote observer for four phases of the TLE during its revolution around the star. The mean TOC values of the four phases of the TLE vary by up to 23 %.

Advanced Concepts and Methods of Approximate Reasoning

DTIC Science & Technology

1989-12-01

immeasurably by numerous conversations and discussions with Nadal Bat- tle, Hamid Berenji , Piero Bonissone, Bernadette Bouchon-Meunier, Miguel Delgado, Di...comments of Claudi Alsina, Hamid Berenji , Piero Bonissone, Didier Dubois, Francesc Esteva, Oscar Firschein, Marty Fischler, Pascal Fua, Maria Angeles

Identification of the epileptogenic zone of temporal lobe epilepsy from stereo-electroencephalography signals: A phase transfer entropy and graph theory approach.

PubMed

Wang, Meng-Yang; Wang, Jing; Zhou, Jian; Guan, Yu-Guang; Zhai, Feng; Liu, Chang-Qing; Xu, Fei-Fei; Han, Yi-Xian; Yan, Zhao-Fen; Luan, Guo-Ming

2017-01-01

The aim of this research is to apply an approach based on phase transfer entropy (PTE) and graph theory to study the interactions between the stereo-electroencephalography (SEEG) activities recorded in multilobar origin, in order to evaluate their ability to detect the epileptogenic zone (EZ) of temporal lobe epilepsies (TLE). Forty-three patients were included in this retrospective study. Five to sixteen (median = 12) multilead electrodes were implanted per patient, and, for each patient, a sub-set of between 10 and 32 (median = 22) bipolar derivations was selected for analysis. The leads were classified into the onset leads (OLs), the early propagation leads (EPLs), and the rest of the leads (RLs). The results showed that a significantly different dynamic trend of the out/in ratio (more obvious in the gamma band) distinguishes the OLs from RLs in the 23 patients who were seizure-free not only during the ictal event (significant elevation), but also during the inter-,pre-, late-ictal periods, and especially in the post-ictal (sharp decline) state. However, in the 20 patients who were not-seizure-free, the differences between the OLs and RLs during the post-ictal period were not found in any frequency band. The dynamic trend was used to predict surgical outcome, and the results showed that the sensitivity was 91% and the specificity was 70%. In brief, this study indicates that our approach may add new and valuable information, providing efficient quantitative measures useful for localizing the EZ.

Accelerated prompt gamma estimation for clinical proton therapy simulations.

PubMed

Huisman, Brent F B; Létang, J M; Testa, É; Sarrut, D

2016-11-07

There is interest in the particle therapy community in using prompt gammas (PGs), a natural byproduct of particle treatment, for range verification and eventually dose control. However, PG production is a rare process and therefore estimation of PGs exiting a patient during a proton treatment plan executed by a Monte Carlo (MC) simulation converges slowly. Recently, different approaches to accelerating the estimation of PG yield have been presented. Sterpin et al (2015 Phys. Med. Biol. 60 4915-46) described a fast analytic method, which is still sensitive to heterogeneities. El Kanawati et al (2015 Phys. Med. Biol. 60 8067-86) described a variance reduction method (pgTLE) that accelerates the PG estimation by precomputing PG production probabilities as a function of energy and target materials, but has as a drawback that the proposed method is limited to analytical phantoms. We present a two-stage variance reduction method, named voxelized pgTLE (vpgTLE), that extends pgTLE to voxelized volumes. As a preliminary step, PG production probabilities are precomputed once and stored in a database. In stage 1, we simulate the interactions between the treatment plan and the patient CT with low statistic MC to obtain the spatial and spectral distribution of the PGs. As primary particles are propagated throughout the patient CT, the PG yields are computed in each voxel from the initial database, as a function of the current energy of the primary, the material in the voxel and the step length. The result is a voxelized image of PG yield, normalized to a single primary. The second stage uses this intermediate PG image as a source to generate and propagate the number of PGs throughout the rest of the scene geometry, e.g. into a detection device, corresponding to the number of primaries desired. We achieved a gain of around 10 3 for both a geometrical heterogeneous phantom and a complete patient CT treatment plan with respect to analog MC, at a convergence level of 2% relative uncertainty in the 90% yield region. The method agrees with reference analog MC simulations to within 10 -4 , with negligible bias. Gains per voxel range from 10 2 to 10 4 . The presented generic PG yield estimator is drop-in usable with any geometry and beam configuration. We showed a gain of three orders of magnitude compared to analog MC. With a large number of voxels and materials, memory consumption may be a concern and we discuss the consequences and possible tradeoffs. The method is available as part of Gate 7.2.

Accelerated prompt gamma estimation for clinical proton therapy simulations

NASA Astrophysics Data System (ADS)

Huisman, Brent F. B.; Létang, J. M.; Testa, É.; Sarrut, D.

2016-11-01

There is interest in the particle therapy community in using prompt gammas (PGs), a natural byproduct of particle treatment, for range verification and eventually dose control. However, PG production is a rare process and therefore estimation of PGs exiting a patient during a proton treatment plan executed by a Monte Carlo (MC) simulation converges slowly. Recently, different approaches to accelerating the estimation of PG yield have been presented. Sterpin et al (2015 Phys. Med. Biol. 60 4915-46) described a fast analytic method, which is still sensitive to heterogeneities. El Kanawati et al (2015 Phys. Med. Biol. 60 8067-86) described a variance reduction method (pgTLE) that accelerates the PG estimation by precomputing PG production probabilities as a function of energy and target materials, but has as a drawback that the proposed method is limited to analytical phantoms. We present a two-stage variance reduction method, named voxelized pgTLE (vpgTLE), that extends pgTLE to voxelized volumes. As a preliminary step, PG production probabilities are precomputed once and stored in a database. In stage 1, we simulate the interactions between the treatment plan and the patient CT with low statistic MC to obtain the spatial and spectral distribution of the PGs. As primary particles are propagated throughout the patient CT, the PG yields are computed in each voxel from the initial database, as a function of the current energy of the primary, the material in the voxel and the step length. The result is a voxelized image of PG yield, normalized to a single primary. The second stage uses this intermediate PG image as a source to generate and propagate the number of PGs throughout the rest of the scene geometry, e.g. into a detection device, corresponding to the number of primaries desired. We achieved a gain of around 103 for both a geometrical heterogeneous phantom and a complete patient CT treatment plan with respect to analog MC, at a convergence level of 2% relative uncertainty in the 90% yield region. The method agrees with reference analog MC simulations to within 10-4, with negligible bias. Gains per voxel range from 102 to 104. The presented generic PG yield estimator is drop-in usable with any geometry and beam configuration. We showed a gain of three orders of magnitude compared to analog MC. With a large number of voxels and materials, memory consumption may be a concern and we discuss the consequences and possible tradeoffs. The method is available as part of Gate 7.2.

Toxic leucoencephalopathy after 'chasing the dragon'.

PubMed

Singh, Rajinder; Saini, Monica

2015-06-01

Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

Light energy attenuation through orthodontic ceramic brackets at different irradiation times.

PubMed

Santini, Ario; Tiu, Szu Hui; McGuinness, Niall J P; Aldossary, Mohammed Saeed

2016-09-01

To evaluate the total light energy (TLE) transmission through three types of ceramic brackets with, bracket alone and with the addition of orthodontic adhesive, at different exposure durations, and to compare the microhardness of the cured adhesive. Three different makes of ceramic brackets, Pure Sapphire(M), Clarity™ ADVANCED(P) and Dual Ceramic(P) were used. Eighteen specimens of each make were prepared and allocated to three groups (n = 6). MARC(®)-resin calibrator was used to determine the light curing unit (LCU) tip irradiance (mW/cm(2)) and TLE (J/cm(2)) transmitted through the ceramic brackets, and through ceramic bracket plus Transbond™ XT Light Cure Adhesive, for 5, 10 and 20 s. Vickers-hardness values at the bottom of the cured adhesive were determined. Statistical analysis used one-way analysis of variance (ANOVA); P = 0.05. TLE transmission rose significantly among all samples with increasing exposure durations. TLE reaching the adhesive- enamel interface was less than 10 J/cm(2), and through monocrystalline and polycrystalline ceramic brackets was significantly different (P < 0.05). Pure Sapphire(M) showed the highest amount of TLE transmission and Vickers-hardness values for 5, 10 and 20 s. Following manufacturer's recommendations, insufficient TLE may be delivered to the adhesive: increasing the exposure durations may be required when adhesive is cured through ceramic brackets. Clinicians are advised to measure the tip irradiance of their LCUs and increase curing time beyond 5 s. Orthodontic clinicians should understand the type of light curing device and the orthodontic adhesive used in their practice.

Structural correlates of impaired working memory in hippocampal sclerosis

PubMed Central

Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S

2013-01-01

Purpose: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. Methods: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Key Findings: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. Significance: Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS. PMID:23614459

Presence of nonlinearity in intracranial EEG recordings: detected by Lyapunov exponents

NASA Astrophysics Data System (ADS)

Liu, Chang-Chia; Shiau, Deng-Shan; Chaovalitwongse, W. Art; Pardalos, Panos M.; Sackellares, J. C.

2007-11-01

In this communication, we performed nonlinearity analysis in the EEG signals recorded from patients with temporal lobe epilepsy (TLE). The largest Lyapunov exponent (Lmax) and phase randomization surrogate data technique were employed to form the statistical test. EEG recordings were acquired invasively from three patients in six brain regions (left and right temporal depth, sub-temporal and orbitofrontal) with 28-32 depth electrodes placed in depth and subdural of the brain. All three patients in this study have unilateral epileptic focus region on the right hippocampus(RH). Nonlinearity was detected by comparing the Lmax profiles of the EEG recordings to its surrogates. The nonlinearity was seen in all different states of the patient with the highest found in post-ictal state. Further our results for all patients exhibited higher degree of differences, quantified by paired t-test, in Lmax values between original and its surrogate from EEG signals recorded from epileptic focus regions. The results of this study demonstrated the Lmax is capable to capture spatio-temporal dynamics that may not be able to detect by linear measurements in the intracranial EEG recordings.

Virtual reality lead extraction as a method for training new physicians: a pilot study.

PubMed

Maytin, Melanie; Daily, Thomas P; Carillo, Roger G

2015-03-01

It is estimated that the demand for transvenous lead extraction (TLE) has reached an annual extraction rate of nearly 24,000 patients worldwide. Despite technologic advances, TLE still has the potential for significant morbidity and mortality. Complication rates with TLE directly parallel operator experience. However, obtaining adequate training during and postfellowship can be difficult. Given the potential for catastrophic complications and the steep learning curve (up to 300 cases) associated with this procedure, we sought to validate a virtual reality (VR) lead extraction simulator as an innovative training and evaluation tool for physicians new to TLE. We randomized eight electrophysiology fellows to VR simulator versus conventional training. We compared procedural skill competency between the groups using simulator competency, tactile measurements, markers of proficiency and attitudes, and cognitive abilities battery. Practical skills and simulator complications differed significantly between the VR simulator and conventional training groups. The VR simulator group executed patient preparation and procedure performance better than the conventional group (P < 0.01). All four fellows randomized to conventional training experienced a simulator complication (two superior vena cava [SVC] tears, three right ventricle [RV] avulsions) versus one fellow in the VR simulator group (one SVC tear) (P = 0.02). Tactile measurements revealed a trend toward excess pushing versus pulling forces among the conventionally trained group. The time for lead removal was also significantly higher in the conventional training group (12.46 minutes vs 5.54 minutes, P = 0.02). There was no significant difference in baseline or posttraining cognitive ability. We contend that the implementation of alternative training tools such as a VR simulation model will improve physician training and allow for an innovative pathway to assess the achievement of competency. ©2014 Wiley Periodicals, Inc.

The association between dopamine receptor (DRD4) gene polymorphisms and second language learning style and behavioral variability in undergraduate students in Turkey.

PubMed

Maras Atabay, Meltem; Safi Oz, Zehra; Kurtman, Elvan

2014-08-01

The dopamine D4 receptor gene (DRD4) encodes a receptor for dopamine, a chemical messenger used in the brain. One variant of the DRD4 gene, the 7R allele, is believed to be associated with attention deficit hyperactivity disorder (ADHD). The aim of this study was to investigate the relationships between repeat polymorphisms in dopamine DRD4 and second language learning styles such as visual (seeing), tactile (touching), auditory (hearing), kinesthetic (moving) and group/individual learning styles, as well as the relationships among DRD4 gene polymorphisms and ADHD in undergraduate students. A total of 227 students between the ages of 17-21 years were evaluated using the Wender Utah rating scale and DSM-IV diagnostic criteria for ADHD. Additionally, Reid's perceptual learning style questionnaire for second language learning style was applied. In addition, these students were evaluated for social distress factors using the list of Threatening Events (TLE); having had no TLE, having had just one TLE or having had two or more TLEs within the previous 6 months before the interview. For DRD4 gene polymorphisms, DNA was extracted from whole blood using the standard phenol/chloroform method and genotyped using polymerase chain reaction. Second language learners with the DRD4.7+ repeats showed kinaesthetic and auditory learning styles, while students with DRD4.7-repeats showed visual, tactile and group learning, and also preferred the more visual learning styles [Formula: see text]. We also demonstrated that the DRD4 polymorphism significantly affected the risk effect conferred by an increasing level of exposure to TLE.

History and Technical Approaches and Considerations for Ablative Surgery for Epilepsy.

PubMed

Sinha, Saurabh; Danish, Shabbar F

2016-01-01

The history of epilepsy surgery is generally noted to have begun in 1886 with Victor Horsley's first report of craniotomies for posttraumatic epilepsy. With increased understanding of brain function and development of electroencephalographic methods, nonlesional epilepsy began to be treated with resection in the 1950s. Methodological improvements and increased understanding of pathophysiology followed, and the advent of stereotaxy and ablative technology in the 1960s and 1970s heralded a new era of minimally invasive, targeted procedures for lesional and nonlesional epilepsy. Current techniques combine stereotactic methods, improved ablative technologies, and electroencephalographic methods for a multidisciplinary approach to the neurosurgical treatment of epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Stone Attenuation Values Measured by Average Hounsfield Units and Stone Volume as Predictors of Total Laser Energy Required During Ureteroscopic Lithotripsy Using Holmium:Yttrium-Aluminum-Garnet Lasers.

PubMed

Ofude, Mitsuo; Shima, Takashi; Yotsuyanagi, Satoshi; Ikeda, Daisuke

2017-04-01

To evaluate the predictors of the total laser energy (TLE) required during ureteroscopic lithotripsy (URS) using the holmium:yttrium-aluminum-garnet (Ho:YAG) laser for a single ureteral stone. We retrospectively analyzed the data of 93 URS procedures performed for a single ureteral stone in our institution from November 2011 to September 2015. We evaluated the association between TLE and preoperative clinical data, such as age, sex, body mass index, and noncontrast computed tomographic findings, including stone laterality, location, maximum diameter, volume, stone attenuation values measured using average Hounsfield units (HUs), and presence of secondary signs (severe hydronephrosis, tissue rim sign, and perinephric stranding). The mean maximum stone diameter, volume, and average HUs were 9.2 ± 3.8 mm, 283.2 ± 341.4 mm 3 , and 863 ± 297, respectively. The mean TLE and operative time were 2.93 ± 3.27 kJ and 59.1 ± 28.1 minutes, respectively. Maximum stone diameter, volume, average HUs, severe hydronephrosis, and tissue rim sign were significantly correlated with TLE (Spearman's rho analysis). Stepwise multiple linear regression analysis defining stone volume, average HUs, severe hydronephrosis, and tissue rim sign as explanatory variables showed that stone volume and average HUs were significant predictors of TLE (standardized coefficients of 0.565 and 0.320, respectively; adjusted R 2  = 0.55, F = 54.7, P <.001). Stone attenuation values measured by average HUs and stone volume were strong predictors of TLE during URS using Ho:YAG laser procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors Controlling the Stable Nitrogen Isotopic Composition (δ15N) of Lipids in Marine Animals

PubMed Central

Svensson, Elisabeth; Schouten, Stefan; Hopmans, Ellen C.; Middelburg, Jack J.; Sinninghe Damsté, Jaap S.

2016-01-01

Lipid extraction of biomass prior to stable isotope analysis is known to cause variable changes in the stable nitrogen isotopic composition (δ15N) of residual biomass. However, the underlying factors causing these changes are not yet clear. Here we address this issue by comparing the δ15N of bulk and residual biomass of several marine animal tissues (fish, crab, cockle, oyster, and polychaete), as well as the δ15N of the extracted lipids. As observed previously, lipid extraction led to a variable offset in δ15N of biomass (differences ranging from -2.3 to +1.8 ‰). Importantly, the total lipid extract (TLE) was highly depleted in 15N compared to bulk biomass, and also highly variable (differences ranging from -14 to +0.7 ‰). The TLE consisted mainly of phosphatidylcholines, a group of lipids with one nitrogen atom in the headgroup. To elucidate the cause for the 15N-depletion in the TLE, the δ15N of amino acids was determined, including serine because it is one of the main sources of nitrogen to N-containing lipids. Serine δ15N values differed by -7 to +2 ‰ from bulk biomass δ15N, and correlated well with the 15N depletion in TLEs. On average, serine was less depleted (-3‰) than the TLE (-7 ‰), possibly due to fractionation during biosynthesis of N-containing headgroups, or that other nitrogen-containing compounds, such as urea and choline, or recycled nitrogen contribute to the nitrogen isotopic composition of the TLE. The depletion in 15N of the TLE relative to biomass increased with the trophic level of the organisms. PMID:26731720

Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification.

PubMed

Yasuoka, Yuuri; Suzuki, Yutaka; Takahashi, Shuji; Someya, Haruka; Sudou, Norihiro; Haramoto, Yoshikazu; Cho, Ken W; Asashima, Makoto; Sugano, Sumio; Taira, Masanori

2014-07-09

Head specification by the head-selector gene, orthodenticle (otx), is highly conserved among bilaterian lineages. However, the molecular mechanisms by which Otx and other transcription factors (TFs) interact with the genome to direct head formation are largely unknown. Here we employ ChIP-seq and RNA-seq approaches in Xenopus tropicalis gastrulae and find that occupancy of the corepressor, TLE/Groucho, is a better indicator of tissue-specific cis-regulatory modules (CRMs) than the coactivator p300, during early embryonic stages. On the basis of TLE binding and comprehensive CRM profiling, we define two distinct types of Otx2- and TLE-occupied CRMs. Using these devices, Otx2 and other head organizer TFs (for example, Lim1/Lhx1 (activator) or Goosecoid (repressor)) are able to upregulate or downregulate a large battery of target genes in the head organizer. An underlying principle is that Otx marks target genes for head specification to be regulated positively or negatively by partner TFs through specific types of CRMs.

CFD study on NACA 4415 airfoil implementing spherical and sinusoidal Tubercle Leading Edge

PubMed Central

2017-01-01

The Humpback whale tubercles have been studied for more than a decade. Tubercle Leading Edge (TLE) effectively reduces the separation bubble size and helps in delaying stall. They are very effective in case of low Reynolds number flows. The current Computational Fluid Dynamics (CFD) study is on NACA 4415 airfoil, at a Reynolds number 120,000. Two TLE shapes are tested on NACA 4415 airfoil. The tubercle designs implemented on the airfoil are sinusoidal and spherical. A parametric study is also carried out considering three amplitudes (0.025c, 0.05c and 0.075c), the wavelength (0.25c) is fixed. Structured mesh is utilized to generate grid and Transition SST turbulence model is used to capture the flow physics. Results clearly show spherical tubercles outperform sinusoidal tubercles. Furthermore experimental study considering spherical TLE is carried out at Reynolds number 200,000. The experimental results show that spherical TLE improve performance compared to clean airfoil. PMID:28850622

CFD study on NACA 4415 airfoil implementing spherical and sinusoidal Tubercle Leading Edge.

PubMed

Aftab, S M A; Ahmad, K A

2017-01-01

The Humpback whale tubercles have been studied for more than a decade. Tubercle Leading Edge (TLE) effectively reduces the separation bubble size and helps in delaying stall. They are very effective in case of low Reynolds number flows. The current Computational Fluid Dynamics (CFD) study is on NACA 4415 airfoil, at a Reynolds number 120,000. Two TLE shapes are tested on NACA 4415 airfoil. The tubercle designs implemented on the airfoil are sinusoidal and spherical. A parametric study is also carried out considering three amplitudes (0.025c, 0.05c and 0.075c), the wavelength (0.25c) is fixed. Structured mesh is utilized to generate grid and Transition SST turbulence model is used to capture the flow physics. Results clearly show spherical tubercles outperform sinusoidal tubercles. Furthermore experimental study considering spherical TLE is carried out at Reynolds number 200,000. The experimental results show that spherical TLE improve performance compared to clean airfoil.

Orthographic Reading Deficits in Dyslexic Japanese Children: Examining the Transposed-Letter Effect in the Color-Word Stroop Paradigm

PubMed Central

Ogawa, Shino; Shibasaki, Masahiro; Isomura, Tomoko; Masataka, Nobuo

2016-01-01

In orthographic reading, the transposed-letter effect (TLE) is the perception of a transposed-letter position word such as “cholocate” as the correct word “chocolate.” Although previous studies on dyslexic children using alphabetic languages have reported such orthographic reading deficits, the extent of orthographic reading impairment in dyslexic Japanese children has remained unknown. This study examined the TLE in dyslexic Japanese children using the color-word Stroop paradigm comprising congruent and incongruent Japanese hiragana words with correct and transposed-letter positions. We found that typically developed children exhibited Stroop effects in Japanese hiragana words with both correct and transposed-letter positions, thus indicating the presence of TLE. In contrast, dyslexic children indicated Stroop effects in correct letter positions in Japanese words but not in transposed, which indicated an absence of the TLE. These results suggest that dyslexic Japanese children, similar to dyslexic children using alphabetic languages, may also have a problem with orthographic reading. PMID:27303331

Orthographic Reading Deficits in Dyslexic Japanese Children: Examining the Transposed-Letter Effect in the Color-Word Stroop Paradigm.

PubMed

Ogawa, Shino; Shibasaki, Masahiro; Isomura, Tomoko; Masataka, Nobuo

2016-01-01

In orthographic reading, the transposed-letter effect (TLE) is the perception of a transposed-letter position word such as "cholocate" as the correct word "chocolate." Although previous studies on dyslexic children using alphabetic languages have reported such orthographic reading deficits, the extent of orthographic reading impairment in dyslexic Japanese children has remained unknown. This study examined the TLE in dyslexic Japanese children using the color-word Stroop paradigm comprising congruent and incongruent Japanese hiragana words with correct and transposed-letter positions. We found that typically developed children exhibited Stroop effects in Japanese hiragana words with both correct and transposed-letter positions, thus indicating the presence of TLE. In contrast, dyslexic children indicated Stroop effects in correct letter positions in Japanese words but not in transposed, which indicated an absence of the TLE. These results suggest that dyslexic Japanese children, similar to dyslexic children using alphabetic languages, may also have a problem with orthographic reading.

Systematic review of epilepsy self-management interventions integrated with a synthesis of children and young people's views and experiences.

PubMed

Lewis, Sheila A; Noyes, Jane; Hastings, Richard P

2015-03-01

To determine the effectiveness of epilepsy self-management interventions and explore the views and experiences of medication and seizures by children and young people. Experiencing seizures and side-effects from anti-epileptic medicines have negative impacts on children and young people managing their epilepsy. Children commonly experiment with not taking epilepsy medication as prescribed and engage in unhealthy lifestyles. DESIGN/REVIEW METHODS: Mixed-method systematic review with theory development. Cochrane quantitative methods and thematic synthesis of qualitative and survey evidence. Eight databases were searched from earliest dates to July 2013. Nineteen studies were included. Meta-analysis was not possible. Zero of nine intervention studies showed improvement in anti-epilepsy medication adherence. Skill-based behavioural techniques with activities such as role play and goal setting with young people increased epilepsy knowledge and seizure self-management (small effects). Intervention studies were methodologically weak and no studies reported if improvement in self-management was sustained over time. Synthesis of nine qualitative and one mixed-method studies generated six themes encapsulating anti-epilepsy medication and epilepsy effects. There was a lack of fidelity between intervention programme theories and what children and young people found difficult with medication self-management and managing the effects of epilepsy. Children and young people knowingly and/or unknowingly take risks with their epilepsy and give reasoned explanations for doing so. There are no effective interventions to change epilepsy medication adherence behaviours. There is an urgent need for more innovative and individually tailored interventions to address specific challenges to epilepsy self-management as identified by children and young people themselves. © 2014 John Wiley & Sons Ltd.

Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.

PubMed

Noé, Francesco M; Bellistri, Elisa; Colciaghi, Francesca; Cipelletti, Barbara; Battaglia, Giorgio; de Curtis, Marco; Librizzi, Laura

2016-06-01

Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue. KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion. Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Cytidine 5'-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death.

PubMed

Kim, Jin Hee; Lee, Dong Won; Choi, Bo Young; Sohn, Min; Lee, Song Hee; Choi, Hui Chul; Song, Hong Ki; Suh, Sang Won

2015-01-21

Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is an important intermediate in the biosynthesis of cell membrane phospholipids. Citicoline serves as a choline donor in the biosynthetic pathways of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. The ability of citicoline to reverse neuronal injury has been tested in animal models of cerebral ischemia and clinical trials have been performed in stroke patients. However, no studies have examined the effect of citicoline on seizure-induced neuronal death. To clarify the potential therapeutic effects of citicoline on seizure-induced neuronal death, we used an animal model of pilocarpine-induced epilepsy. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25mg/kg) in adult male rats. Citicoline (100 or 300 mg/kg) was injected into the intraperitoneal space two hours after seizure onset and a second injection was performed 24h after the seizure. Citicoline was injected once per day for one week after pilocarpine- or kainate-induced seizure. Neuronal injury and microglial activation were evaluated at 1 week post-seizure. Surprisingly, rather than offering protection, citicoline treatment actually enhanced seizure-induced neuronal death and microglial activation in the hippocampus compared to vehicle treated controls. Citicoline administration after seizure-induction increased immunoglobulin leakage via BBB disruption in the hippocampus compared with the vehicle-only group. To clarify if this adverse effect of citicoline is generalizable across alternative seizure models, we induced seizure by kainate injection (10mg/kg, i.p.) and then injected citicoline as in pilocarpine-induced seizure. We found that citicoline did not modulate kainate seizure-induced neuronal death, BBB disruption or microglial activation. These results suggest that citicoline may not have neuroprotective effects after seizure and that clinical application of citicoline after seizure needs careful consideration. Copyright © 2014 Elsevier B.V. All rights reserved.

Anticonvulsant medications attenuate amphetamine-induced deficits in behavioral inhibition but not decision making under risk on a rat gambling task.

PubMed

Tremblay, Melanie; Winstanley, Catharine A

2016-11-01

Impulsivity is a major component of mania in bipolar disorder (BD), and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are observed in some patients with temporal lobe epilepsy (TLE), and incidence of problem gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of BD. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioral aspect targeted by these drugs. This project explored the effect of the three anticonvulsant drugs currently also used as mood stabilizers- carbamazepine, valproate and lamotrigine on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). In this task, rats choose between four distinct, probabilistic reinforcement schedules. Sugar pellet profits are maximized by adopting a conservative strategy, avoiding tempting high-risk, high-reward options. Effects of the anticonvulsant agents were assessed on baseline performance and also in conjunction with amphetamine administration, in order to approximate a "mania-like" state. Carbamazepine appeared to slow processing speed, decreasing premature responses and increasing choice latency, whereas valproate and lamotrigine had no effect. When administered prior to amphetamine, lamotrigine was the only drug that failed to attenuate the pro-impulsive effect of the psychostimulant. Further studies looking at chronic administration of anticonvulsants may help us understand the impact of this medication class on decision-making and impulsivity in healthy rats and disease models. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay.

PubMed

Laporte, Aimée N; Ji, Jennifer X; Ma, Limin; Nielsen, Torsten O; Brodin, Bertha A

2016-06-07

Conventional cytotoxic therapies for synovial sarcoma provide limited benefit. Drugs specifically targeting the product of its driver translocation are currently unavailable, in part because the SS18-SSX oncoprotein functions via aberrant interactions within multiprotein complexes. Proximity ligation assay is a recently-developed method that assesses protein-protein interactions in situ. Here we report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known.

TLE TeachLive™: Using Technology to Provide Quality Professional Development in Rural Schools

ERIC Educational Resources Information Center

Dieker, Lisa A.; Hynes, Michael C.; Hughes, Charles E.; Hardin, Stacey; Becht, Kathleen

2015-01-01

Rural schools face challenges in training and retaining qualified teachers, especially special education personnel. This article describes how an interdisciplinary team at the University of Central Florida developed TLE TeachLivE™, a virtual reality application designed to serve as a classroom simulation to support teachers and administrators to…

The Use of Visual-Based Simulated Environments in Teacher Preparation

ERIC Educational Resources Information Center

Judge, Sharon; Bobzien, Jonna; Maydosz, Ann; Gear, Sabra; Katsioloudis, Petros

2013-01-01

While virtual technology for training in the simulation field has a long history in medicine, aviation, and the military, the application of similar emerging and innovative technologies in teacher preparation and education has been limited. TLE TeachLive™ (Teaching Learning Environment, Teaching in a Virtual Environment) [TLE] is an inventive…

Transformative Learning Experience: Aim Higher, Gain More

ERIC Educational Resources Information Center

Wilson, Brent G.; Parrish, Patrick E.

2011-01-01

A transformative learning experience (TLE) is an especially meaningful encounter that leaves a lasting impact on a person's sense of competence or place in the world. The construct of TLE is presented in transactional terms as an irreducible interplay between learner and the world (including the natural world, artifacts, and other people).…

A phospholipase A1 antibacterial Type VI secretion effector interacts directly with the C-terminal domain of the VgrG spike protein for delivery.

PubMed

Flaugnatti, Nicolas; Le, Thi Thu Hang; Canaan, Stéphane; Aschtgen, Marie-Stéphanie; Nguyen, Van Son; Blangy, Stéphanie; Kellenberger, Christine; Roussel, Alain; Cambillau, Christian; Cascales, Eric; Journet, Laure

2016-03-01

The Type VI secretion system (T6SS) is a multiprotein machine that delivers protein effectors in both prokaryotic and eukaryotic cells, allowing interbacterial competition and virulence. The mechanism of action of the T6SS requires the contraction of a sheath-like structure that propels a needle towards target cells, allowing the delivery of protein effectors. Here, we provide evidence that the entero-aggregative Escherichia coli Sci-1 T6SS is required to eliminate competitor bacteria. We further identify Tle1, a toxin effector encoded by this cluster and showed that Tle1 possesses phospholipase A1 and A2 activities required for the interbacterial competition. Self-protection of the attacker cell is secured by an outer membrane lipoprotein, Tli1, which binds Tle1 in a 1:1 stoichiometric ratio with nanomolar affinity, and inhibits its phospholipase activity. Tle1 is delivered into the periplasm of the prey cells using the VgrG1 needle spike protein as carrier. Further analyses demonstrate that the C-terminal extension domain of VgrG1, including a transthyretin-like domain, is responsible for the interaction with Tle1 and its subsequent delivery into target cells. Based on these results, we propose an additional mechanism of transport of T6SS effectors in which cognate effectors are selected by specific motifs located at the C-terminus of VgrG proteins. © 2015 John Wiley & Sons Ltd.

The cost-effectiveness of sacral nerve stimulation (SNS) for the treatment of idiopathic medically refractory overactive bladder (wet) in the UK.

PubMed

Autiero, Silke Walleser; Hallas, Natalie; Betts, Christopher D; Ockrim, Jeremy L

2015-12-01

To estimate the long-term cost-effectiveness of specialised treatment options for medically refractory idiopathic overactive bladder (OAB) wet. The cost-effectiveness of competing treatment options for patients with medically refractory idiopathic OAB wet was estimated from the perspective of the National Health Service in the UK. We compared sacral nerve stimulation (SNS) with percutaneous nerve evaluation (PNE) or tined-lead evaluation (TLE) with optimal medical therapy (OMT), botulinum toxin type A (BoNT-A) injections, and percutaneous tibial nerve stimulation (PTNS). We used a Markov model with a 10-year time horizon for all treatment options with the exception of PTNS, which has a time horizon of 5 years. Costs and effects (measured as quality-adjusted life years) were calculated to derive incremental cost-effectiveness ratios (ICERs). Direct medical resources included are: device and drug acquisition costs, pre-procedure and procedure costs, and the cost of managing adverse events. Deterministic sensitivity analyses were performed to test robustness of results. At 5 years, SNS (PNE or TLE) was more effective and less costly than PTNS. Compared with OMT at 10 years, SNS (PNE or TLE) was more costly and more effective, and compared with BoNT-A, SNS PNE was less costly and more effective, and SNS TLE was more costly and more effective. Decreasing the BoNT-A dose from 150 to 100 IU marginally increased the 10 year ICERs for SNS TLE and PNE (SNS PNE was no longer dominant). However, both SNS options remained cost-effective. In the management of patients with idiopathic OAB wet, the results of this cost-utility analysis favours SNS (PNE or TLE) over PTNS or OMT, and the most efficient treatment strategy is SNS PNE over BoNT-A over a 10-year period. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

The direct cost of epilepsy in the United States: A systematic review of estimates.

PubMed

Begley, Charles E; Durgin, Tracy L

2015-09-01

To develop estimates of the direct cost of epilepsy in the United States for the general epilepsy population and sub-populations by systematically comparing similarities and differences in types of estimates and estimation methods from recently published studies. Papers published since 1995 were identified by systematic literature search. Information on types of estimates, study designs, data sources, types of epilepsy, and estimation methods was extracted from each study. Annual per person cost estimates from methodologically similar studies were identified, converted to 2013 U.S. dollars, and compared. From 4,104 publications discovered in the literature search, 21 were selected for review. Three were added that were published after the search. Eighteen were identified that reported estimates of average annual direct costs for the general epilepsy population in the United States. For general epilepsy populations (comprising all clinically defined subgroups), total direct healthcare costs per person ranged from $10,192 to $47,862 and epilepsy-specific costs ranged from $1,022 to $19,749. Four recent studies using claims data from large general populations yielded relatively similar epilepsy-specific annual cost estimates ranging from $8,412 to $11,354. Although more difficult to compare, studies examining direct cost differences for epilepsy sub-populations indicated a consistent pattern of markedly higher costs for those with uncontrolled or refractory epilepsy, and for those with comorbidities. This systematic review found that various approaches have been used to estimate the direct costs of epilepsy in the United States. However, recent studies using large claims databases and similar methods allow estimation of the direct cost burden of epilepsy for the general disease population, and show that it is greater for some patient subgroups. Additional research is needed to further understand the broader economic burden of epilepsy and how it varies across subpopulations. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

PubMed

Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin

2016-11-01

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Microchip-based electrochemical detection using a 3-D printed wall-jet electrode device.

PubMed

Munshi, Akash S; Martin, R Scott

2016-02-07

Three dimensional (3-D) printing technology has evolved dramatically in the last few years, offering the capability of printing objects with a variety of materials. Printing microfluidic devices using this technology offers various advantages such as ease and uniformity of fabrication, file sharing between laboratories, and increased device-to-device reproducibility. One unique aspect of this technology, when used with electrochemical detection, is the ability to produce a microfluidic device as one unit while also allowing the reuse of the device and electrode for multiple analyses. Here we present an alternate electrode configuration for microfluidic devices, a wall-jet electrode (WJE) approach, created by 3-D printing. Using microchip-based flow injection analysis, we compared the WJE design with the conventionally used thin-layer electrode (TLE) design. It was found that the optimized WJE system enhances analytical performance (as compared to the TLE design), with improvements in sensitivity and the limit of detection. Experiments were conducted using two working electrodes - 500 μm platinum and 1 mm glassy carbon. Using the 500 μm platinum electrode the calibration sensitivity was 16 times higher for the WJE device (as compared to the TLE design). In addition, use of the 1 mm glassy carbon electrode led to limit of detection of 500 nM for catechol, as compared to 6 μM for the TLE device. Finally, to demonstrate the versatility and applicability of the 3-D printed WJE approach, the device was used as an inexpensive electrochemical detector for HPLC. The number of theoretical plates was comparable to the use of commercially available UV and MS detectors, with the WJE device being inexpensive to utilize. These results show that 3-D-printing can be a powerful tool to fabricate reusable and integrated microfluidic detectors in configurations that are not easily achieved with more traditional lithographic methods.

Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis.

PubMed

Zhu, Hongyan; Zhao, Yuxiao; Wu, Hao; Jiang, Nan; Wang, Ziyi; Lin, Weide; Jin, Jiahui; Ji, Yonghua

2016-12-01

Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ). A prominent, seizure intensity-dependent increase of Nav1.6 expression in reactive astrocytes was observed in ipsilateral hippocampus of post-SE rats, reaching the peak at 21 days after SE, a time point during the latent stage of epileptogenesis. However, Nav1.6 with low expression level was selectively expressed in the hippocampal neurons rather than astrocytes in PTZ-kindled animals. This seizure-related increase of a VGSCs subtype in reactive astrocytes after SE may represent a new mechanism for signal communication between neuron and glia in the course of epileptogenesis, facilitating the neuronal hyperexcitability.

Classroom Simulation to Prepare Teachers to Use Evidence-Based Comprehension Practices

ERIC Educational Resources Information Center

Ely, Emily; Alves, Kat D.; Dolenc, Nathan R.; Sebolt, Stephanie; Walton, Emily A.

2018-01-01

Reading comprehension is an area of weakness for many students, including those with disabilities. Innovative technology methods may play a role in improving teacher readiness to use evidence-based comprehension practices for all students. In this experimental study, researchers examined a classroom simulation (TLE TeachLivE™) to improve…