EEG, PET, SPET and MRI in intractable childhood epilepsies: possible surgical correlations.

PubMed

Fois, A; Farnetani, M A; Balestri, P; Buoni, S; Di Cosmo, G; Vattimo, A; Guazzelli, M; Guzzardi, R; Salvadori, P A

1995-12-01

Magnetic resonance imaging (MRI), single photon emission tomography (SPET), and positron emission tomography (PET) using [18F]fluorodeoxyglucose were used in combination with scalp and scalp-video EEGs in a group of 30 pediatric patients with drug resistant epilepsy (DRE) in order to identify patients who could benefit from neurosurgical approach. Seizures were classified according to the consensus criteria of The International League Against Epilepsy. In three patients infantile spasms (IS) were diagnosed; 13 subjects were affected by different types of generalized seizures, associated with complex partial seizures (CPS) in three. In the other 14 patients partial seizures, either simple (SPS) or complex, were present. A localized abnormality was demonstrated in one patient with IS and in three patients with generalized seizures. Of the group of 14 subjects with CPS, MRI and CT were normal in 7, but SPET or PET indicated focal hypoperfusion or hypometabolism concordant with the localization of the EEG abnormalities. In 5 of the other 7 patients anatomical and functional imaging and EEG findings were concordant for a localized abnormality. It can be concluded that functional imaging combined with scalp EEGs appears to be superior to the use of only CT and MRI for selecting children with epilepsy in whom a surgical approach can be considered, in particular when CPS resistant to therapy are present.

Seizure-related factors and non-verbal intelligence in children with epilepsy. A population-based study from Western Norway.

PubMed

Høie, B; Mykletun, A; Sommerfelt, K; Bjørnaes, H; Skeidsvoll, H; Waaler, P E

2005-06-01

To study the relationship between seizure-related factors, non-verbal intelligence, and socio-economic status (SES) in a population-based sample of children with epilepsy. The latest ILAE International classifications of epileptic seizures and syndromes were used to classify seizure types and epileptic syndromes in all 6-12 year old children (N=198) with epilepsy in Hordaland County, Norway. The children had neuropediatric and EEG examinations. Of the 198 patients, demographic characteristics were collected on 183 who participated in psychological studies including Raven matrices. 126 healthy controls underwent the same testing. Severe non-verbal problems (SNVP) were defined as a Raven score at or <10th percentile. Children with epilepsy were highly over-represented in the lowest Raven percentile group, whereas controls were highly over-represented in the higher percentile groups. SNVP were present in 43% of children with epilepsy and 3% of controls. These problems were especially common in children with remote symptomatic epilepsy aetiology, undetermined epilepsy syndromes, myoclonic seizures, early seizure debut, high seizure frequency and in children with polytherapy. Seizure-related characteristics that were not usually associated with SNVP were idiopathic epilepsies, localization related (LR) cryptogenic epilepsies, absence and simple partial seizures, and a late debut of epilepsy. Adjusting for socio-economic status factors did not significantly change results. In childhood epilepsy various seizure-related factors, but not SES factors, were associated with the presence or absence of SNVP. Such deficits may be especially common in children with remote symptomatic epilepsy aetiology and in complex and therapy resistant epilepsies. Low frequencies of SNVP may be found in children with idiopathic and LR cryptogenic epilepsy syndromes, simple partial or absence seizures and a late epilepsy debut. Our study contributes to an overall picture of cognitive function and its relation to central seizure characteristics in a childhood epilepsy population and can be useful for the follow-up team in developing therapy strategies that meet the individual needs of the child with epilepsy.

Genetics Home Reference: malignant migrating partial seizures of infancy

MedlinePlus

... of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures ... infantile epileptic encephalopathy 14 EIEE14 malignant migrating partial epilepsy of infancy migrating partial epilepsy of infancy migrating ...

Genetics Home Reference: autosomal dominant partial epilepsy with auditory features

MedlinePlus

... Twitter Home Health Conditions ADPEAF Autosomal dominant partial epilepsy with auditory features Printable PDF Open All Close ... the expand/collapse boxes. Description Autosomal dominant partial epilepsy with auditory features ( ADPEAF ) is an uncommon form ...

How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit.

PubMed

Jenssen, Sigmund; Gracely, Edward J; Sperling, Michael R

2006-09-01

More information is needed regarding how long seizures typically last, since this influences treatment decisions. Seizure type and other factors could influence seizure duration. Data were collected from a random sample of patients being evaluated with continuous video and scalp EEG. Seizure duration was defined as time from early sign of seizure (clinical or EEG) until the end of seizure on EEG. Seizures were categorized as simple partial (SPS), complex partial (CPS), secondarily generalized tonic-clonic (SGTCS), primary generalized tonic-clonic (PGTCS) and tonic (TS). SGTCS were divided into a complex partial part (SGTCS/CP) and a tonic-clonic part (SGTCS/TC). Median and longest duration of each seizure type in each individual were used. Comparisons of seizure types, first and last seizure, area of onset, and state of onset were performed. Five hundred seventy-nine seizures were recorded in 159 adult patients. Seizures with partial onset spreading to both hemispheres had the longest duration. SGTCS were unlikely to last more than 660 s, CPS more than 600 s, and SPS more than 240 s. PGTCS and TS had shorter durations, but the number of subjects with those two types was small. CPS did not differ in duration according to sleep state at onset nor side of origin. A working definition of status epilepticus in adults with cryptogenic or symptomatic epilepsy can be drawn from these data for purposes of future epidemiologic research. More information is needed for the idiopathic epilepsies and in children.

Treatment of pediatric epilepsy in Poland.

PubMed

Dunin-Wąsowicz, Dorota; Mazurkiewicz-Bełdzińska, Maria; Steinborn, Barbara; Wheless, James; Jóźwiak, Sergiusz

2015-05-01

The many types of childhood epilepsies make the diagnosis and treatment difficult and the outcomes frequently poor. Furthermore, there are few clinical trials in pediatric epilepsy that provide useful results to guide daily practice. Therefore for pediatric neurologists expert opinion may be useful. To provide an overview of current practice in Poland and compare results with European and US clinical guidelines. Polish specialists in pediatric neurology were asked to participate in a survey about pediatric epilepsy. The focus of the questions was on the overall strategy and treatment options for different syndromic diagnoses. The survey was developed and performed according to a previous European survey (Wheless et al., 2007). Fifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen. Polish pediatric neurologists agreed on the majority of questions. Their views reflect the clinical utility and availability of treatment options in Poland. Results may provide direction for clinicians. Copyright © 2015. Published by Elsevier Ltd.

The consequences of idiopathic partial epilepsies in relation to neuropsychological functioning: a closer look at the associated mathematical disability.

PubMed

Sart, Z Hande; Demirbilek, Veysi; Korkmaz, Bariş; Slade, Peter D; Dervent, Ayşin; Townes, Brenda D

2006-03-01

Although the seizure prognosis is mostly favorable in idiopathic partial epilepsies, there is some empirical evidence showing that subtle neuropsychological impairments, with a consequent risk of academic underachievement, are not rare. We investigated neuropsychological functioning including attention, memory, visuomotor ability, and executive functioning with a closer look at the associated mathematical ability in patients with idiopathic partial epilepsies. A battery of age-appropriate, neuropsychological and mathematics achievement tests was administered to 30 participants with idiopathic partial epilepsy [13 children with benign epilepsy with centrotemporal spikes (BECTS), 17 children with idiopathic childhood occipital epilepsies (ICOE)], and to 30 healthy participants matched for age, sex, handedness, and socioeconomic status. Results did not support any impairment in overall neuropsychological functioning in participants with idiopathic partial epilepsies, whereas, isolated deficits did exist. The mean performance of the IPE group was significantly lower than the control group in six out of 12, neuropsychological measures: drawing (p < 0.01), digit span (p < 0.05), verbal learning (p < 0.01), object assembly (p < 0.01), similarities (p < 0.05), and vocabulary (p < 0.001). Results suggested that one should be cautious regarding neuropsychological and academic prognosis in the so-called benign idiopathic partial epilepsies of childhood.

Affective temperament profiles and clinical correlates in patients with epilepsy: a link from mood disorders.

PubMed

Erdoğan Taycan, Serap; Taycan, Okan

2014-08-01

The current study sought to investigate the affective temperaments of patients with epilepsy and possible relationships between disease characteristics and temperament profiles. A total of 70 adults with epilepsy and 70 healthy volunteers completed the Beck Depression Inventory (BDI), the Beck Anxiety Inventory and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A). Patients with epilepsy had higher scores on these three scales than healthy controls. With respect to temperaments, irritable temperament alone was significantly higher in patients than controls. Irritable temperament also had a significant positive correlation with psychiatric history, whereas depressive temperament had a significant positive correlation with illness and treatment duration. Patients who had suffered simple partial and complex partial seizures had higher anxious temperament scores than patients with generalized epilepsy. Because the study group was recruited through consecutive patients seen in a single neurology clinic, our findings may not be representative of PWE in general. Because irritability is one of the key symptoms of interictal dysphoric disorder and because TEMPS-A irritable temperament and BDI scores were found to be significantly related, the high rate of irritable temperament in our patient sample may be associated with depressive mood. We may suggest that at least some of the affective symptoms in patients with epilepsy and the historical concept of "epileptic personality" may be explained by affective temperaments. Copyright © 2014 Elsevier B.V. All rights reserved.

Basic mechanisms of gabitril (tiagabine) and future potential developments.

PubMed

Meldrum, B S; Chapman, A G

1999-01-01

Gabitril (tiagabine) is a potent selective inhibitor of the principal neuronal gamma-aminobutyric acid (GABA) transporter (GAT-1) in the cortex and hippocampus. By slowing the reuptake of synaptically-released GABA, it prolongs inhibitory postsynaptic potentials. In animal models of epilepsy, tiagabine is particularly effective against kindled (limbic) seizures and against reflexly-induced generalized convulsive seizures. These data are predictive of its efficacy in complex partial seizures in humans. Possible clinical applications outside the field of epilepsy include bipolar disorder and pain.

Temporal Lobe Epilepsy Semiology

PubMed Central

Blair, Robert D. G.

2012-01-01

Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone. PMID:22957241

Partial (focal) seizure

MedlinePlus

... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

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.

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

Sleep and Epilepsy: Strange Bedfellows No More.

PubMed

St Louis, Erik K

2011-09-01

Ancient philosophers and theologians believed that altered consciousness freed the mind to prophesy the future, equating sleep with seizures. Only recently has the bidirectional influences of epilepsy and sleep upon one another received more substantive analysis. This article reviews the complex and increasingly recognized interrelationships between sleep and epilepsy. NREM sleep differentially activates interictal epileptiform discharges during slow wave (N3) sleep, while ictal seizure events occur more frequently during light NREM stages N1 and N2. The most commonly encountered types of sleep-related epilepsies (those with preferential occurrence during sleep or following arousal) include frontal and temporal lobe partial epilepsies in adults, and benign epilepsy of childhood with centrotemporal spikes (benign rolandic epilepsy) and juvenile myoclonic epilepsy in children and adolescents. Comorbid sleep disorders are frequent in patients with epilepsy, particularly obstructive sleep apnea in refractory epilepsy patients which may aggravate seizure burden, while treatment with nasal continuous positive airway pressure often improves seizure frequency. Distinguishing nocturnal events such as NREM parasomnias (confusional arousals, sleep walking, and night terrors), REM parasomnias including REM sleep behavior disorder, and nocturnal seizures if frequently difficult and benefits from careful history taking and video-EEG-polysomnography in selected cases. Differentiating nocturnal seizures from primary sleep disorders is essential for determining appropriate therapy, and recognizing co-existent sleep disorders in patients with epilepsy may improve their seizure burden and quality of life.

A comparison of the efficacy and tolerability of oxcarbazepine oral suspension between infants and children with epilepsy: a retrospective chart review at a single medical center in Taiwan.

PubMed

Wei, Shu-Hao; Liu, Cheng-Chao; Fan, Pi-Chuan

2014-02-01

Few clinical studies have assessed the efficacy and safety of oxcarbazepine (OXC) oral suspension in Asian pediatric patients and particularly in infants. The aim of this study was to investigate and compare the efficacy, tolerability, and side effects of OXC oral suspension in Taiwanese infants and children with various types of epilepsy. A retrospective review of the efficacy, tolerability, and side effects of OXC oral suspension in a tertiary medical center in Taiwan was conducted and included children (1-9 years old) and infants (<1 year old) diagnosed with epilepsy, which was classified into idiopathic partial, symptomatic partial, or multifocal subtypes. The OXC oral suspension (Trileptal(®); Novartis) was given in a gradual dose titration, from an initial 7.5 mg/kg/day to 30 mg/kg/day within 1 month in all cases. A total of 20 infants and 38 children were identified. There were no statistically significant differences between the children and infants in efficacy (75 vs. 82 %, p = 0.734) and adverse effects (30 vs. 21 %, p = 0.525) after OXC oral suspension treatment. The efficacy was significantly correlated with the epilepsy subtype (p < 0.01) and the number of combined antiepileptic drugs (AEDs) before OXC treatment (p < 0.01) in both groups. The patients with idiopathic and symptomatic partial epilepsy responded better to OXC oral suspension than those with multifocal epilepsy. OXC oral suspension is effective and well tolerated in both infants and children with partial epilepsy in Taiwan. Treatment efficacy was related to epilepsy subtype and number of combined AEDs before OXC treatment. Monotherapy had an excellent therapeutic response in partial epilepsy but not in multifocal epilepsy.

Genetics of Severe Early Onset Epilepsies

ClinicalTrials.gov

2017-08-24

Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions

Controlling Seizures

ERIC Educational Resources Information Center

Henderson, Nancy

2008-01-01

This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…

Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms

PubMed Central

Lerner, Jason T; Salamon, Noriko; Sankar, Raman

2010-01-01

Vigabatrin, the first therapeutic agent to be approved by the Food and Drug Administration for the treatment of infantile spasms, as well as for adjunctive use in the treatment of refractory complex partial epilepsy, represents an important advance for patients with difficult-to-manage epilepsy. This review summarizes the complex history, chemistry, and pharmacology, as well as the clinical data leading to the approval of vigabatrin for infantile spasms in the US. The long path to its approval reflects the visual system and white matter toxicity concerns with this agent. This review provides a brief description of these concerns, and the regulatory safety monitoring and mitigation systems that have been put in place to enhance benefit over risk. PMID:21127692

Health care resource utilization in patients with active epilepsy.

PubMed

Kurth, Tobias; Lewis, Barbara E; Walker, Alexander M

2010-05-01

To evaluate health care resource utilization (HRU) in active epilepsy. Thomson-Reuters insurance databases included 14 million persons in 2005-2007. We extracted information for individuals with insurance claims suggestive of epilepsy. Using iterative expert classification, we sorted patients by type of epilepsy. For each type we calculated prevalence and HRU. A distance analysis identified closely similar types, and a principal components analysis revealed dimensions of variation in HRU. The prevalence of active epilepsy was 3.4 per 1,000. Most common diagnoses among 46,847 patients were generalized convulsive epilepsy (33.3%) and complex partial seizures (24.8%). Patients averaged 10 physician visits per year, 24 diagnostic tests/procedures per year, >30 drug dispensings per year, and <1 emergency room (ER) visit per year, the minority of each of these being related to epilepsy. Female patients generally had more HRU, and HRU increased with age. Patients were hospitalized most frequently for disorders other than epilepsy. HRU was similar for most epilepsy types, excepting grand mal status, epilepsia partialis continua, and infantile spasms. The first principal components of HRU variation was nonepilepsy HRU, followed by components of epilepsy-related medications, other epilepsy/emergency care, and epilepsy visits/diagnostic procedures. The prevalence of active epilepsy in the United States is substantially less than the prevalence of any history of recurrent seizure. Nonepilepsy-related HRU dominated HRU in epilepsy patients and was the principal source of variation. There is a core set of epilepsy diagnoses, the HRU patterns of which are indistinguishable, whereas patients with grand mal status, epilepsia partialis continua, and infantile spasms all have distinct patterns. To provide more specific insights into the economic impact of the condition, studies of HRU in epilepsy should make a distinction about epilepsy-related and unrelated care.

The origin of the concept of partial epilepsy.

PubMed

Eadie

1999-03-01

The International League Against Epilepsy has devised classifications which subdivide both epileptic seizures and the epilepsies and epileptic syndromes into two main types: generalized and partial. Epileptogenesis in the partial variety is believed to originate in a localized part of the cerebral cortex and results in clinical manifestations which appear to commence in only a restricted part of the sufferer's body. Use of the term 'partial' in relation to these entities has often been said to date back to James Cowles Prichard (1786-1849) who was the author of the second major work on epilepsy to be written in the UK. While Prichard certainly described 'partial epilepsy', he stated that he intended the words to refer to the fact that the disorder he described under that designation was only partly, and not fully, epileptic in nature. He did not refer to the fact that it affected only part of the body as his basis for using the term. In the absence of knowledge of localization of function in the cerebral cortex at Prichard's time of writing, he had no basis for deducing that the underlying epileptic process arose in only part of the brain. However, there is an earlier mention of the use of the word 'partial' in relation to epilepsy. This is to be found in the writings of the great Scottish physician William Cullen (1710-1790), and there is reason to believe that Prichard should have been aware of this. Cullen used 'partial' with an intention similar to the modern one, employing the word to refer to seizures which affected only part of the body. Credit for the origin of the idea of a 'partial' epilepsy should belong to Cullen; not only did he have priority over Prichard but his concept was closer to the modern one than was Prichard's. Copyright 1999 Harcourt Publishers Ltd.

A young infant with musicogenic epilepsy.

PubMed

Lin, Kuang-Lin; Wang, Huei-Shyong; Kao, Pan-Fu

2003-05-01

Musicogenic epilepsy is a relatively rare form of epilepsy. In its pure form, it is characterized by epileptic seizures that are provoked exclusively by listening to music. The usual type of seizure is partial complex or generalized tonic-clonic. Precipitating factors are quite specific, such as listening to only one composition or the actual playing of music on an instrument. However, simple sound also can be a trigger. We report a 6-month-old infant with musicogenic epilepsy. She manifested right-sided focal seizures with occasional generalization. The seizures were frequently triggered by loud music, especially that by the Beatles. The interictal electroencephalography results were normal. Ictal spikes were present throughout the left temporal area during continuous electroencephalograpic monitoring. Brain magnetic resonance imaging results were normal, whereas single-photon emission computed tomography of the brain revealed hypoperfusion of the left temporal area. The young age and epileptogenic left temporal lobe lesion in this patient with musicogenic epilepsy were unusual characteristics. Theoretically, three levels of integration are involved in music processing in the brain. The involved integration of this infant's brain may be the sensory level rather than the emotional level. Nevertheless, the personal musicality and musical style of the Beatles might play an important role in this patient's epilepsy.

Prolonged partial epilepsy: a case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, M.A.

1980-11-01

The case study of a patient with prolonged partial epilepsy is presented. There was a discrepancy between the extent of the abnormality seen on the radionuclide angiogram and that seen on the static brain scan.

Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy.

PubMed

Deonna, Thierry; Roulet, Eliane

2006-01-01

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.

Epilepsy surgery in a liver-transplanted girl with temporal lobe epilepsy and hippocampal sclerosis following PRES with status epilepticus.

PubMed

Dilena, Robertino; Nebbia, Gabriella; Fiorica, Lorenzo; Farallo, Marcello; Degrassi, Irene; Gozzo, Francesca; Pelliccia, Veronica; Barbieri, Sergio; Cossu, Massimo; Tassi, Laura

2016-07-01

Posterior reversible encephalopathy syndrome (PRES) with status epilepticus may occur after liver transplant. This may rarely lead to refractory epilepsy and hippocampal sclerosis (HS). We report the first case of epilepsy surgery in a liver-transplanted patient with refractory temporal lobe epilepsy. A 3-year-old girl underwent liver transplant for congenital biliary atresia. Four days after transplant she manifested PRES with status epilepticus, but she recovered within a couple of weeks. At the age of 5 years she started presenting complex partial seizures, that became refractory to antiepileptic drugs (AED), worsening psychosocial performances. The pre-surgical work-up identified a left HS and temporal pole alterations. A left antero-mesial temporal lobectomy was performed, leading to epilepsy remission and allowing AED withdrawal. Drug-resistant temporal lobe epilepsy and HS may occur as sequelae of PRES with status epilepticus related to liver transplant and cyclosporine use. In this setting early epilepsy surgery may reduce the time of chronic exposure to AED and severe illness due to repeated seizures. This option might have additional advantages in the subgroup of epileptic patients with liver transplant, preserving the liver from the potential damage due to multiple AED trials and their interaction with commonly used immunosuppressant drugs. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

WITHDRAWN: Oxcarbazepine add-on for drug-resistant partial epilepsy.

PubMed

Castillo, Sergio M; Schmidt, Dieter B; White, Sarah; Shukralla, Arif

2016-11-15

Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome. Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy, both in adults and children. However, trials reviewed were of relatively short duration, and provide no evidence about the long-term effects of oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with other epilepsy types.

Impaired Consciousness in Epilepsy

PubMed Central

Blumenfeld, Hal

2013-01-01

Consciousness is essential to normal human life. In epileptic seizures consciousness is often transiently lost making it impossible for the individual to experience or respond. This has huge consequences for safety, productivity, emotional health and quality of life. To prevent impaired consciousness in epilepsy it is necessary to understand the mechanisms leading to brain dysfunction during seizures. Normally the “consciousness system”—a specialized set of cortical-subcortical structures—maintains alertness, attention and awareness. Recent advances in neuroimaging, electrophysiology and prospective behavioral testing have shed new light on how epileptic seizures disrupt the consciousness system. Diverse seizure types including absence, generalized tonic-clonic and complex partial seizures converge on the same set of anatomical structures through different mechanisms to disrupt consciousness. Understanding these mechanisms may lead to improved treatment strategies to prevent impaired consciousness and improve quality of life in people with epilepsy. PMID:22898735

Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or adverse effect of vagal nerve stimulation?

PubMed

Akman, Cigdem; Riviello, James J; Madsen, Joseph R; Bergin, Ann M

2003-06-01

Sensory symptoms are commonly seen in association with focal epilepsy, but viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main clinical manifestation. With the introduction of vagal nerve stimulation (VNS) for medically refractory epilepsy, viscerosensory symptoms commonly occur as an adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local neck or throat pain, and cough are the most common adverse effects seen during active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a tingling sensation of the neck and throat is directly related to stimulation intensity. We present a case in which recurrent pharyngeal sensations caused a diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and correlating this with clinical symptoms helped determine the etiology of the recurrent sensory symptoms.

Efficacy of low to moderate doses of oxcarbazepine in adult patients with newly diagnosed partial epilepsy.

PubMed

Zou, Xue-Mei; Chen, Jia-Ni; An, Dong-Mei; Hao, Nan-Ya; Hong, Zhen; Hao, Xiao-Ting; Rao, Ping; Zhou, Dong

2015-07-01

The objective of this study was to explore the efficacy of low dose of oxcarbazepine (OXC) in adult patients with newly diagnosed partial epilepsy in an actual clinical setting. The associated factors influencing the poor control of seizures were also evaluated. The epilepsy database (2010-2014) from the Epilepsy Clinic of West China Hospital was retrospectively reviewed. A total of 102 adult patients with newly diagnosed, previously untreated partial epilepsy initially treated with OXC were included, and divided into good response group (64) and poor response group (38) according to whether they were seizure-free for at least 12 months. There were 27 (26.5%) patients becoming seizure-free with OXC 600 mg/day monotherapy. The remaining 75 patients had doses of either increasing OXC to 900 mg/day (n = 59) or the addition of another antiepileptic drug (AED) (n = 16), with another 20 (19.6%) and six (5.9%) patients becoming seizure-free, respectively (P = 0.788). In addition, two (2.0%) and nine (8.8%) patients became seizure-free with OXC > 900 mg/day monotherapy and OXC ≥ 900 mg/day combination therapy, respectively. Multivariate binary logistic regression analysis revealed that the time from onset of epilepsy to treatment initiation is significantly associated with seizure control (P = 0.02). Our results indicated that OXC at low to moderate doses is effective for the treatment of Chinese adult patients with newly diagnosed, previously untreated partial epilepsy, and a longer time interval from the onset of epilepsy to the start of treatment significantly predicts poor seizure control. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy

NASA Technical Reports Server (NTRS)

Blum, A. S.; Ives, J. R.; Goldberger, A. L.; Al-Aweel, I. C.; Krishnamurthy, K. B.; Drislane, F. W.; Schomer, D. L.

2000-01-01

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

PubMed

Nguyen, Dang Khoa; Rochette, Emilie; Leroux, Jean-Maxime; Beaudoin, Gilles; Cossette, Patrick; Lassonde, Maryse; Guilbert, François

2010-10-01

High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.5 T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI. We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0 T MR study after a negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist. Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery. The frequency of detection of a new lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. 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.

Mood, anxiety, and incomplete seizure control affect quality of life after epilepsy surgery

PubMed Central

Blackmon, Karen; Cong, Xiangyu; Dziura, James; Atlas, Lauren Y.; Vickrey, Barbara G.; Berg, Anne T.; Bazil, Carl W.; Langfitt, John T.; Walczak, Thaddeus S.; Sperling, Michael R.; Shinnar, Shlomo; Devinsky, Orrin

2014-01-01

Objective: We examined the complex relationship between depression, anxiety, and seizure control and quality of life (QOL) outcomes after epilepsy surgery. Methods: Seven epilepsy centers enrolled 373 patients and completed a comprehensive diagnostic workup and psychiatric and follow-up QOL evaluation. Subjects were evaluated before surgery and then at 3, 6, 12, 24, 48, and 60 months after surgery. Standardized assessments included the Quality of Life in Epilepsy Inventory–89, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). A mixed-model repeated-measures analysis was used to analyze associations of depression, anxiety, seizure outcome, and seizure history with overall QOL score and QOL subscores (cognitive distress, physical health, mental health, epilepsy-targeted) prospectively. Results: The groups with excellent and good seizure control showed a significant positive effect on the overall QOL compared to the groups with fair and poor seizure control. The BDI and BAI scores were both highly and negatively associated with overall QOL; increases in BDI and BAI scores were associated with decreased overall QOL score. Conclusions: Depression and anxiety are strongly and independently associated with worse QOL after epilepsy surgery. Interestingly, even partial seizure control, controlling for depression and anxiety levels, improved QOL. Management of mood and anxiety is a critical component to postsurgical care. PMID:24489129

Quality of life after surgery for intractable partial epilepsy in children: a cohort study with controls.

PubMed

Mikati, Mohamad A; Ataya, Nour; Ferzli, Jessica; Kurdi, Rana; El-Banna, Diana; Rahi, Amal; Shamseddine, Alhan; Sinno, Durriyah; Comair, Youssef

2010-08-01

Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children. This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire). In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p>0.05) but had lower scores in the total QOL, physical, and health domains (p<0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p<0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p<0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p<0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p>0.05, power>0.8). Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

Calcified neurocysticercosis lesions and hippocampal sclerosis: potential dual pathology?

PubMed

Rathore, Chaturbhuj; Thomas, Bejoy; Kesavadas, Chandrasekharan; Radhakrishnan, Kurupath

2012-04-01

In areas where cysticercosis is endemic, calcified neurocysticercosis lesion(s) (CNL) and hippocampal sclerosis (HS) commonly coexist in patients with localization-related epilepsies. To understand the pathogenesis of HS associated with CNL, we compared the characteristics of three groups of patients with antiepileptic drug-resistant epilepsies: CNL with HS, CNL without HS (CNL alone), and HS without CNL (HS alone). In comparison to patients with CNL alone, those with CNL with HS had CNL more frequently located in the ipsilateral temporal lobe. Those with CNL with HS had a lower incidence of febrile seizures, older age at initial precipitating injury and at onset of habitual complex partial seizures, and more frequent clustering of seizures and extratemporal/bitemporal interictal epileptiform discharges as compared to patients with HS alone. Our study illustrates that HS associated with CNL might have a different pathophysiologic basis as compared to classical HS. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Pituitary adenoma with seizures: PET demonstration of reduced glucose utilization in the medial temporal lobe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bairamian, D.; Di Chiro, G.; Blume, H.

1986-05-01

A patient with a benign chromophobe adenoma, who had incomplete surgical removal followed by radiotherapy, continued to have epileptic seizures up to two or three times a day. She was studied with positron emission tomography using /sup 18/F-2-deoxyglucose (FDG). This technique showed a high level of glucose utilization in the area of the operated tumor but also clear reduction of glucose utilization in the left medial temporal region adjacent to the sella and the scar tissue from the neoplasm. This area of reduced glucose utilization corresponded well to the same finding observed in other patients with complex partial epilepsy. Amore » left temporal anterior lobectomy was carried out followed by improved control of the epilepsy. Positron emission tomography using FDG, together with electrophysiological examinations, may assist in the management of epilepsy related to pituitary tumors.« less

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

Unfavorable surgical outcomes in partial epilepsy with secondary bilateral synchrony: Intracranial electroencephalography study.

PubMed

Sunwoo, Jun-Sang; Byun, Jung-Ick; Moon, Jangsup; Lim, Jung-Ah; Kim, Tae-Joon; Lee, Soon-Tae; Jung, Keun-Hwa; Park, Kyung-Il; Chu, Kon; Kim, Manho; Chung, Chun-Kee; Jung, Ki-Young; Lee, Sang Kun

2016-05-01

Secondary bilateral synchrony (SBS) indicates bilaterally synchronous epileptiform discharges arising from a focal cortical origin. The present study aims to investigate SBS in partial epilepsy with regard to surgical outcomes and intracranial EEG findings. We retrospectively reviewed consecutive patients who underwent epilepsy surgery following extraoperative intracranial electroencephalography (EEG) study from 2008 to 2012. The presence of SBS was determined based upon the results of scalp EEG monitoring performed for presurgical evaluations. We reviewed scalp EEG, neuroimaging, intracranial EEG findings, and surgical outcomes in patients with SBS. We found 12 patients with SBS who were surgically treated for intractable partial epilepsy. Nine (75%) patients had lateralized ictal semiology and only two (16.6%) patients showed localized ictal onset in scalp EEG. Brain MRI showed epileptogenic lesion in three (25%) patients. Intracranial EEG demonstrated that ictal onset zone was widespread or non-localized in six (50%) patients. Low-voltage fast activity was the most common ictal onset EEG pattern. Rapid propagation of ictal onset was noted in 10 (83.3%) patients. Eleven patients underwent resective epilepsy surgery and only two patients (18.2%) achieved seizure-freedom (median follow-up 56 months). MRI-visible brain lesions were associated with favorable outcomes (p=0.024). Patients with SBS, compared to frontal lobe epilepsy without SBS, showed lesser localization in ictal onset EEG (p=0.029) and more rapid propagation during evolution of ictal rhythm (p=0.015). The present results suggested that resective surgery for partial epilepsy with SBS should be decided carefully, especially in case of nonlesional epilepsy. Poor localization and rapid spread of ictal onset were prominent in intracranial EEG, which might contribute to incomplete resection of the epileptogenic zone and poor surgical outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

First seizure while driving (FSWD)--an underestimated phenomenon?

PubMed

Pohlmann-Eden, Bernd; Hynick, Nina; Legg, Karen

2013-07-01

Seizures while driving are a well known occurrence in established epilepsy and have significant impact on driving privileges. There is no data available on patients who experience their first (diagnosed) seizure while driving (FSWD). Out of 311 patients presenting to the Halifax First Seizure Clinic between 2008 and 2011, 158 patients met the criteria of a first seizure (FS) or drug-naïve, newly diagnosed epilepsy (NDE). A retrospective chart review was conducted. FSWD was evaluated for 1) prevalence, 2) clinical presentation, 3) coping strategies, and 4) length of time driving before seizure occurrence. The prevalence of FSWD was 8.2%. All 13 patients experienced impaired consciousness. Eleven patients had generalized tonic-clonic seizures, one starting with a déjà-vu evolving to visual aura and a complex partial seizure; three directly from visual auras. Two patients had complex partial seizures, one starting with an autonomic seizure. In response to their seizure, patients reported they were i) able to actively stop the car (n=4, three had visual auras), ii) not able to stop the car resulting in accident (n=7), or iii) passenger was able to pull the car over (n=2). One accident was fatal to the other party. Twelve out of 13 patients had been driving for less than one hour. FSWD is frequent and possibly underrecognized. FSWD often lead to accidents, which occur less if preceded by simple partial seizures. Pathophysiological mechanisms remain uncertain; it is still speculative if complex visuo-motor tasks required while driving play a role in this scenario.

Prevalence and risk factors of seizure clusters in adult patients with epilepsy.

PubMed

Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Wong, Rebecca A; Jiang, Alfred; Kato, Kenneth; Buchsbaum, Richard; Detyniecki, Kamil

2017-07-01

In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. We reviewed medical records of 4116 adult (≥16years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P<0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P<0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also independently increase one's chance of having seizure clusters. Copyright © 2017. Published by Elsevier B.V.

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly.

PubMed

Tanaka, Akihiro; Akamatsu, Naoki; Shouzaki, Taisaku; Toyota, Tomoko; Yamano, Mitsuhiko; Nakagawa, Masanori; Tsuji, Sadatoshi

2013-11-01

Epidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan. We searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded. We identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n=33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n=50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n=51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year. The most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Smoking prevalence and seizure control in Chinese males with epilepsy.

PubMed

Gao, Hui; Sander, Josemir W; Du, Xudong; Chen, Jiani; Zhu, Cairong; Zhou, Dong

2017-08-01

Smoking has a negative effect on most diseases, yet it is under-investigated in people with epilepsy; thus its role is not clear in the general population with epilepsy. We performed a retrospective pilot study on males with epilepsy to determine the smoking rate and its relationship with seizure control using univariate analysis to calculate odds ratios (ORs) and also used a multi-variate logistic regression model. The smoking rate in our sample of 278 individuals was 25.5%, which is lower than the general Chinese population smoking rate among males of 52.1%. We used two classifications: the first classified epilepsy as generalized, or by presumed topographic origin (temporal, frontal, parietal and occipital). The second classified the dominant seizure type of an individual as generalized tonic clonic seizure (GTCS), myoclonic seizure (MS), complex partial seizure (CPS), simple partial seizure (SPS), and secondary GTCS (sGTCS). The univariable analysis of satisfactory seizure control profile and smoking rate in both classifications showed a trend towards a beneficial effect of smoking although most were not statistically significant. Considering medication is an important confounding factor that would largely influence seizure control, we also conducted multi-variable analysis for both classifications with drug numbers and dosage. The result of our model also suggested that smoking is a protective factor. Our findings seem to suggest that smoking could have a potential role in seizure control although confounders need exploration particularly in view of the potential long term health effects. Replication in a much larger sample is needed as well as case control studies to elucidate this issue. Copyright © 2017 Elsevier Inc. All rights reserved.

Seizures induced by music.

PubMed

Ogunyemi, A O; Breen, H

1993-01-01

Musicogenic epilepsy is a rare disorder. Much remains to be learned about the electroclinical features. This report describes a patient who has been followed at our institution for 17 years, and was investigated with long-term telemetered simultaneous video-EEG recordings. She began to have seizures at the age of 10 years. She experienced complex partial seizures, often preceded by elementary auditory hallucination and complex auditory illusion. The seizures occurred in relation to singing, listening to music or thinking about music. She also had occasional generalized tonic clonic seizures during sleep. There was no significant antecedent history. The family history was negative for epilepsy. The physical examination was unremarkable. CT and MRI scans of the brain were normal. During long-term simultaneous video-EEG recordings, clinical and electrographic seizure activities were recorded in association with singing and listening to music. Mathematical calculation, copying or viewing geometric patterns and playing the game of chess failed to evoke seizures.

Cognitive predictors of adaptive functioning in children with symptomatic epilepsy.

PubMed

Kerr, Elizabeth N; Fayed, Nora

2017-10-01

The current study sought to understand the contribution of the attention and working memory challenges experienced by children with active epilepsy without an intellectual disability to adaptive functioning (AF) while taking into account intellectual ability, co-occurring brain-based psychosocial diagnoses, and epilepsy-related variables. The relationship of attention and working memory with AF was examined in 76 children with active epilepsy with intellectual ability above the 2nd percentile recruited from a tertiary care center. AF was measured using the Scales of Independent Behavior-Revised (SIB-R) and compared with norm-referenced data. Standardized clinical assessments of attention span, sustained attention, as well as basic and more complex working memory were administered to children. Commonality analysis was used to investigate the importance of the variables with respect to the prediction of AF and to construct parsimonious models to elucidate the factors most important in explaining AF. Seventy-one percent of parents reported that their child experienced mild to severe difficulties with overall AF. Similar proportions of children displayed limitations in domain-specific areas of AF (Motor, Social/Communication, Person Living, and Community Living). The reduced models for Broad and domain-specific AF produced a maximum of seven predictor variables, with little loss in overall explained variance compared to the full models. Intellectual ability was a powerful predictor of Broad and domain-specific AF. Complex working memory was the only other cognitive predictor retained in each of the parsimonious models of AF. Sustained attention and complex working memory explained a large amount of the total variance in Motor AF. Children with a previously diagnosed comorbidity displayed lower Social/Communication, Personal Living, and Broad AF than those without a diagnosis. At least one epilepsy-related variable appeared in each of the reduced models, with age of seizure onset and seizure type (generalized or partial) being the main predictors. Intellectual ability was the most powerful predictor of AF in children with epilepsy whose intellectual functioning was above the 2nd percentile. Co-occurring brain-based cognitive and psychosocial issues experienced by children with living epilepsy, particularly complex working memory and diagnosed comorbidities, contribute to AF and may be amenable to intervention. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Quantifying interictal metabolic activity in human temporal lobe epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.

1990-09-01

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on (18F)fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a singlemore » investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.« less

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

Patterns of language and auditory dysfunction in 6-year-old children with epilepsy.

PubMed

Selassie, Gunilla Rejnö-Habte; Olsson, Ingrid; Jennische, Margareta

2009-01-01

In a previous study we reported difficulty with expressive language and visuoperceptual ability in preschool children with epilepsy and otherwise normal development. The present study analysed speech and language dysfunction for each individual in relation to epilepsy variables, ear preference, and intelligence in these children and described their auditory function. Twenty 6-year-old children with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y-6 y 11 mo) and 30 reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range 6 y-6 y 11 mo) were assessed for language and auditory ability. Low scores for the children with epilepsy were analysed with respect to speech-language domains, type of epilepsy, site of epileptiform activity, intelligence, and language laterality. Auditory attention, perception, discrimination, and ear preference were measured with a dichotic listening test, and group comparisons were performed. Children with left-sided partial epilepsy had extensive language dysfunction. Most children with partial epilepsy had phonological dysfunction. Language dysfunction was also found in children with generalized and unclassified epilepsies. The children with epilepsy performed significantly worse than the reference children in auditory attention, perception of vowels and discrimination of consonants for the right ear and had more left ear advantage for vowels, indicating undeveloped language laterality.

The new patient with a first seizure.

PubMed

King, Mark

2003-04-01

First seizures are common, with one in 20 people suffering a seizure at some time in their life. This article aims to outline the assessment of patients with a first seizure, including making an accurate diagnosis of both seizure type and an epilepsy syndrome, if present. Seizures are classified into generalised and partial (arising from a focal region in the brain) based on clinical and electroencephalogram findings. However, as a partial seizure may proceed to a tonic clonic phase, differentiation may be difficult. Inquiring directly about 'minor' epileptic symptoms before the episode such as absences, myoclonic jerks, visual or auditory hallucinations or feelings of déjà vu, is needed to attempt to make a epilepsy syndrome diagnosis, as this has practical implications for treatment, prognosis and genetic counselling. Generalised epilepsies should be treated initially with valproate, while partial epilepsies should be treated with carbamazepine and switched to newer agents if intolerance occurs.

"I heard voices...": from semiology, a historical review, and a new hypothesis on the presumed epilepsy of Joan of Arc.

PubMed

d'Orsi, Giuseppe; Tinuper, Paolo

2006-08-01

Some consider the "voices" of Joan of Arc to have been ecstatic epileptic auras, such as Dostoevsky's epilepsy. We performed a critical analysis of this hypothesis and suggest that the "voices" may be the expression of an epileptic syndrome recently described: idiopathic partial epilepsy with auditory features (IPEAF). Joan's symptoms were obtained from the documentation of her Trial of Condemnation. We investigated Joan of Arc from a strictly semiologic point of view, focusing on symptoms and possible trigger factors. From ages 13 to 19, the episodes were characterized by a prevalent auditory component, followed by "a great light" or images that Joan identified as saints. Sometimes, the visual component was missing and replaced by comprehension verbal disturbance. The spells were sudden, brief in duration, and frequent, and also occurred during sleep. In some cases, the sound of bells could trigger the "voices." Joan's spells were characterized by a constant auditory component, complex, spontaneous, or evoked by sudden auditory stimuli, that could be associated with an inconstant visual component, sometimes simple and, more often, complex, and comprehension verbal disturbance. These spells differ from ecstatic epilepsy with respect to clinical features and involvement of cerebral regions. The negative family history, the ictal semiology, and the possibility that the spells were triggered by acoustic stimuli suggest IPEAF, and the search for the epitempin/LGI1 gene or other new gene mutations on a hair of the Maid of Orléans may enhance our knowledge about her presumed epilepsy.

High spirituality may be associated with right hemispheric lateralization in Korean adults living with epilepsy.

PubMed

Lee, Sang-Ahm; Ko, Myung-Ah; Choi, Eun-Ju; Jeon, Ji-Ye; Ryu, Han Uk

2017-11-01

Although it is known that epilepsy and spirituality are related, spirituality in epilepsy has received relatively little clinical and scientific attention. Therefore, we investigated which epilepsy-related factors are associated with high spirituality in Korean adults living with epilepsy. This cross-sectional study was conducted in two university hospitals in Korea. Spirituality was assessed using the 6-item Spirituality Self-Rating Scale (SSRS). The participants were categorized into high and low spirituality groups according to the median SSRS score. The presumptive seizure onset zone was determined based on the clinical semiology, electroencephalography, and magnetic resonance imaging findings. Of the 180 participants, 61.7% declared that they had a religious affiliation. The median SSRS score was 15 (interquartile range: 7, 22). The high spirituality subgroup consisted of 92 (51.1%) participants. In the univariate analyses, the high spirituality group was significantly associated with female sex (p<0.05), older age (p<0.01), longer epilepsy duration (p<0.05), polytherapy (p<0.05), complex partial seizure (p<0.05), levetiracetam or topiramate usage (p<0.05), and a right-lateralized seizure onset zone. The multiple logistic regression analysis identified right hemispheric lateralization as the only independent factor associated with high spirituality (odds ratio: 2.410, 95% confidence interval: 1.051-5.528, p<0.05). High spirituality may be associated with right hemispheric lateralization but not with the temporal localization of the seizure onset zone in Korean adults with epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

A clinimetric approach to assessing quality of life in epilepsy.

PubMed

Cramer, J A

1993-01-01

Clinimetrics is a concept involving the use of rating scales for clinical phenomena ranging from physical examinations to functional performance. Clinimetric or rating scales can be used for defining patient status and changes that occur during long-term observation. The scores derived from such scales can be used as guidelines for intervention, treatment, or prediction of outcome. In epilepsy, clinimetric scales have been developed for assessing seizure frequency, seizure severity, adverse effects related to antiepileptic drugs (AEDs), and quality of life after surgery for epilepsy. The VA Epilepsy Cooperative Study seizure rating scale combines frequency and severity in a weighted scoring system for simple and complex partial and generalized tonic-clonic seizures, summing all items in a total seizure score. Similarly, the rating scales for systemic toxicity and neurotoxicity use scores weighted for severity for assessing specific adverse effects typically related to AEDs. A composite score, obtained by adding the scores for seizures, systemic toxicity, and neurotoxicity, represents the overall status of the patient at a given time. The Chalfont Seizure Severity Scale also applies scores relative to the impact of a given item on the patient, without factoring in seizure frequency. The Liverpool Seizure Severity Scale is a patient questionnaire covering perceived seizure severity and the impact of ictal and postictal events. The UCLA Epilepsy Surgery Inventory (ESI-55) assesses quality of life for patients who have undergone surgery for epilepsy using generic health status instruments with additional epilepsy-specific items.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic symptoms during childhood partial epileptic seizures.

PubMed

Fogarasi, András; Janszky, József; Tuxhorn, Ingrid

2006-03-01

To analyze systematically the occurrence and age dependence as well as the localizing and lateralizing value of ictal autonomic symptoms (ASs) during childhood partial epilepsies and to compare our results with those of earlier adult studies. Five hundred fourteen video-recorded seizures of 100 consecutive children 12 years or younger with partial epilepsy and seizure-free postoperative outcome were retrospectively analyzed. Sixty patients produced at least one AS; 43 (70%) of 61 with temporal and 17 (44%) of 39 with extratemporal lobe epilepsy (p=0.012). Apnea/bradypnea occurred more frequently in younger children (p<0.01), whereas the presence of other ASs was neither age nor gender related. Postictal coughing (p<0.01) and epigastric aura (p<0.05) localized to the temporal lobe, whereas no ASs lateralized to the seizure-onset zone. Our study shows that ASs are common in childhood focal epilepsies, appearing in infants and young children, too. As in adults, childhood central autonomic networks might have a close connection to temporal lobe structures but do not lateralize the seizure-onset zone. To our knowledge, this is the first study comprehensively assessing ASs in childhood epilepsy.

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection

PubMed Central

Rosenberg, Evan C.; Patra, Pabitra H.; Whalley, Benjamin J.

2017-01-01

The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB1R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB1R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant cannabinoids, most notably cannabidiol (CBD) and cannabidavarin (CBDV), in models of seizures, epilepsy, epileptogenesis, and neuroprotection are less ambiguous, and consistent with reports of therapeutically beneficial effects of these compounds in clinical studies. However, continued paucity of firm information regarding the therapeutic molecular mechanism of CBD/CBDV highlights the continued need for research in this area in order to identify as yet under-exploited targets for drug development and raise our understanding of treatment-resistant epilepsies. The recent reporting of positive results for cannabidiol treatment in two Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid in epilepsy. Moreover, risks and/or benefits associated with the use of unlicensed Δ9-THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review's findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy. PMID:28190698

[Clinical pattern of epilepsy with abortive temporal lobe attacks].

PubMed

Dowzenko, A; Niedzielska-Zawadzka, K; Witkowska-Olearska, K; Jakubowska, T

1977-01-01

The purpose of the present work was to evaluate the clinical course of epilepsy with infrequent partial attacks with complex manifestations derived from the temporal lobe. Thirty patients aged 14 to 64 years treated on an outpatient basis and discovered during epidemiological investigations were followed-up. In half the cases only attacks without generalization occurred, in the remaining cases isolated generalized seizures appeared during many years of disease duration. In both groups a decrease was observed in the frequency of seizures in patients treated systematically or irregularly, as well as in those who had never been treated. Despite a long duration of the disease (above 6 years in 24 cases) the patients had normal mental level and good social adaptation.

Soren Kierkegaard (1813-55): a bicentennial pathographical review.

PubMed

Schioldann, Johan; Søgaard, Ib

2013-12-01

Researchers in the fields of psychology, psychiatry, medicine and theology have made exhaustive efforts to shed light on the elusive biography/pathography of the great Danish philosopher Søren Kierkegaard (1813-55). This 'bicentennial' article reviews his main pathographical diagnoses of, respectively, possible manic-depressive [bipolar] disease, epilepsy, complex partial seizure disorder, Landry-Guillain-Barré's acute ascending paralysis, acute intermittent porphyria with possible psychiatric manifestations, and syphilidophobia.

Perceived self-control of seizures in patients with uncontrolled partial epilepsy.

PubMed

Lee, Sang-Ahm; No, Young-Joo

2005-03-01

Many patients with epilepsy have warning symptoms prior to seizure onset, and some of these individuals report the ability to abort or prevent these seizures. We investigated the clinical characteristics of perceived self-control of seizures in 174 patients with uncontrolled partial epilepsy. The warning symptoms were categorized as premonitory (prodrome) and as initial symptoms of simple partial seizure onset, depending on the relationship between the warning events and the ensuing seizures. About 50% of the patients with simple partial seizure onset and about 70% of those with prodrome or premonitory symptoms reported that they could abort or prevent their seizures by various self-developed techniques. Patients who attempted to abort or prevent their seizures reported success rates as high as 80%. The proportion of patients with secondary generalized seizures was significantly lower in patients who tried to abort their seizures than in those who did not (p<0.05). The ability to prevent seizures was significantly higher in patients with brain lesions on MRI than in those without lesions (p<0.05). These results suggest that spontaneously developed methods are helpful in controlling seizures in some patients with uncontrolled partial epilepsy and that the potential success of self-control methods may be influenced by structural abnormalities on brain MRI.

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

Complex Phenotype of a Boy With De Novo 16p13.3-13.2 Interstitial Deletion

PubMed Central

Ferrari, Anna Rita; Pasquariello, Rosa; Bargagna, Stefania

2016-01-01

Interstitial deletions encompassing chromosome 16p13.3-13.2 are rarely described in the literature, whereas terminal deletions or duplications involving this region are slightly more frequently described. The authors describe a boy harboring a de novo 16p13.3-13.2 interstitial deletion, with intellectual disability, verbal dyspraxia, epilepsy, and a distinctive brain magnetic resonance finding, namely a nodular heterotopia. The authors found partial genotype–phenotype correspondences regarding epilepsy and intellectual disability, which have been associated with 16p1 region. Conversely, nodular heterotopia and verbal dyspraxia have not been clearly related to this region. These data are in agreement with the emerging concept that similar copy number variants may be the general risk factors for distinct disorders. Verbal dyspraxia, which has not responded to speech therapy, is the child’s most disabling trait. In view of the above, genetic studies should be appraised in cases of serious speech difficulties, especially if they are associated with intellectual disability and epilepsy. PMID:28503620

Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy.

PubMed Central

Nashef, L; Walker, F; Allen, P; Sander, J W; Shorvon, S D; Fish, D R

1996-01-01

OBJECTIVE--To record non-invasively ictal cardiorespiratory variables. METHODS--Techniques employed in polysomnography were used in patients with epilepsy undergoing EEG-video recording at a telemetry unit. RESULTS--Apnoea (> 10, range > 10-63, mean 24 s) was seen in 20 of 47 clinical seizures (three secondary generalised, 16 complex partial, and one tonic) and 10 of 17 patients. Apnoea was central in 10 patients, but obstructive apnoea was also recorded in three of 10. Oxyhaemoglobin saturation (SpO2) dropped to less than 85% in 10 seizures (six patients). An increase in heart rate was common (91% of seizures). Bradycardia/sinus arrest was documented in four patients (mean maximum RR interval 5.36, range 2.8-8.6 s) but always in the context of a change in respiratory pattern. CONCLUSION--Ictal apnoea was often seen. The occurrence of bradycardia in association with apnoea suggests the involvement of cardiorespiratory reflexes. Similar mechanisms may operate in cases of sudden death in epilepsy. PMID:8609507

"God has sent me to you": Right temporal epilepsy, left prefrontal psychosis.

PubMed

Arzy, Shahar; Schurr, Roey

2016-07-01

Religious experiences have long been documented in patients with epilepsy, though their exact underlying neural mechanisms are still unclear. Here, we had the rare opportunity to record a delusional religious conversion in real time in a patient with right temporal lobe epilepsy undergoing continuous video-EEG. In this patient, a messianic revelation experience occurred several hours after a complex partial seizure of temporal origin, compatible with postictal psychosis (PIP). We analyzed the recorded resting-state EEG epochs separately for each of the conventional frequency bands. Topographical analysis of the bandpass filtered EEG epochs revealed increased activity in the low-gamma range (30-40Hz) during religious conversion compared with activity during the patient's habitual state. The brain generator underlying this activity was localized to the left prefrontal cortex. This suggests that religious conversion in PIP is related to control mechanisms in the prefrontal lobe-related processes rather than medial temporal lobe-related processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

PubMed

Rosenberg, Evan C; Patra, Pabitra H; Whalley, Benjamin J

2017-05-01

The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB 1 R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB 1 R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant cannabinoids, most notably cannabidiol (CBD) and cannabidavarin (CBDV), in models of seizures, epilepsy, epileptogenesis, and neuroprotection are less ambiguous, and consistent with reports of therapeutically beneficial effects of these compounds in clinical studies. However, continued paucity of firm information regarding the therapeutic molecular mechanism of CBD/CBDV highlights the continued need for research in this area in order to identify as yet under-exploited targets for drug development and raise our understanding of treatment-resistant epilepsies. The recent reporting of positive results for cannabidiol treatment in two Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid in epilepsy. Moreover, risks and/or benefits associated with the use of unlicensed Δ 9 -THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review's findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy. This article is part of a Special Issue titled Cannabinoids and Epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Experience with rufinamide in a pediatric population: a single center's experience.

PubMed

Vendrame, Martina; Loddenkemper, Tobias; Gooty, Vasu D; Takeoka, Masanori; Rotenberg, Alexander; Bergin, Ann M; Eksioglu, Yaman Z; Poduri, Annapurna; Duffy, Frank H; Libenson, Mark; Bourgeois, Blaise F; Kothare, Sanjeev V

2010-09-01

Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes. Copyright 2010 Elsevier Inc. All rights reserved.

[The efficacy of lacosamide in relation to antiepileptic drug history. Clinical experiences in adult partial epilepsy].

PubMed

Barcs Gábor; Szűcs, Anna; Horváth, András; Kamondi, Anita

2015-01-30

A retrospective study in adult partial epilepsy on the efficacy of lacosamide in relation to previous antiepileptic drug experiences. We analysed 3-65 months' data on epilepsy-care of 43 pharmacoresistant partial epilepsy patients treated with lacosamide. Further analysis of antiepileptic drug history was carried out in strictly selected subgroups of patients with good and poor therapeutic response to lacosamide (10 and 9 patients, respectively) for 2-10 years long retrospective follow up. Adult patients with partial-onset seizures had been treated previously with three or more lifetime antiepileptic drugs without permanent success. Six patients (14%) were seizure free, eleven patients (25%) have experienced important improvement (their seizure-frequency decreased by at least 50%) for more than 12 months. Fourteen patients (32%) improved for less than 6 months and then have relapsed; and add-on lacosamide proved ineffective in 12 patients (28%). Those selected 10 patients successfully treated with lacosamide (seizure free for at least six months) favourably responded to carbamazepine or oxcarbazepine earlier and levetiracetam was ineffective or even caused worsening. The selected lacosamide-unresponsive nine patients responded unfavourably to carbamazepine or oxcarbazepine earlier. Fifteen patients (35%) suffered side effects as dizziness or sleepiness, in 11 of them lacosamide was combined with a "traditional" sodium-channal blocker antiepileptic drug. Lacosamide is an effective add-on antiepileptic drug in difficult-to treat adult partial epilepsy patients. Our data suggest that good lacosamide response may be expected in those patients who reacted favourably to "traditional" sodium-channel blocker carbamazepine or oxcarbazepine earlier.

Malformations of cortical development and epilepsy: evaluation of 101 cases (part II).

PubMed

Güngör, Serdal; Yalnizoğlu, Dilek; Turanli, Güzide; Saatçi, Işil; Erdoğan-Bakar, Emel; Topçu, Meral

2007-01-01

Malformations of cortical development (MCD) form a spectrum of lesions produced by insult to the developing neocortex. Clinical presentation and electrophysiologic findings of MCD are variable and depend on the affected cortical area. We evaluated epilepsy, EEG, and response to antiepileptic treatment in patients with MCD with respect to the neuroimaging findings. We studied 101 patients, ranging between 1 month and 19 years of age. Fifty-four patients were diagnosed with polymicrogyria (PMG), 23 patients with lissencephaly, 12 patients with schizencephaly, and 12 patients with heterotopia. With regards to epilepsy and seizure type, 72/101 (71.3%) patients had epilepsy, and 62/101 (61.4%) patients presented with seizures. Overall, 32.7% of patients had generalized seizures, and 25.7% had complex partial seizures. Mean age at the onset of seizures was 2.7 +/- 3.4 years. The onset of epilepsy tended to be younger in patients with lissencephaly and older in patients with heterotopias. Of the cases, 79.2% had abnormal EEG (56.3% with epileptiform abnormality, 22.9% with non-epileptiform abnormality). EEG was abnormal in 44.9% (13/29) of the cases without epilepsy. EEG showed bilateral synchronous and diffuse epileptiform discharges in 90% of patients with lissencephaly. Patients with schizencephaly had mostly focal epileptiform discharges. Heterotopia cases had a high rate of EEG abnormalities (72.7%). Patients with PMG had epileptiform abnormality in 59.5% of the cases. Patients with heterotopias and PMG achieved better seizure control in comparison with the other groups. In conclusion, epilepsy is the most common problem in MCD. Epilepsy and EEG findings of patients with MCD are variable and seem to be correlated with the extent of cortical involvement.

Epilepsy in children with subacute sclerosing panencephalitis.

PubMed

Jović, Nebojša J

2013-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, fatal neurodegenerative disease of childhood and early adolescence caused by defective measles virus. The initial symptoms of SSPE usually involve regression in cognitive functioning and behavior or recurrent myoclonic jerks. Seizures revealing SSPE and epilepsy during the clinical course can occur. The aim of the study was to analyze clinical and EEG characteristics of both initially occurred seizures and epilepsy which developed in the course of the disease. Retrospective study was carried out on 19 children (14 boys, 5 girls) with SSPE diagnosed and treated at our Clinic from 1995 to 2010. Seizures revealed SSPE in our patients aged from 6.5 to 11.5 years (mean 8.6 years). SSPE onset ranged from 4.5 to 16.5 years (mean 10.05). Complete vaccination was performed in nine patients. Cognitive and behavioral decline was preceeded by 6-18 months in two children with intractable focal motor seizures with secondary generalization, one child with complex partial seizures and one with atypical absences. During the clinical course of the disease epilepsy developed in 10 (52.6%) cases, including four patients with seizures as the initial SSPE sign. It occurred mainly in the first year, while in three cases seizures appeared between 1 and 5 years of the disease evolution. Myoclonus was present independently from seizures. No significant inter-group differences were found relating to the type of SSPE progression and history of epilepsy. The only child with fulminant SSPE presented with initial seizures. Favorable seizure control was achieved in 60.0% patients. Intractable epilepsy developed in four patients. Atypical SSPE presentation can include mainly focal intractable seizures. Epilepsy developed during clinical course in 52.6% cases. No significant influence was found of the history of epilepsy on the type of SSPE progression.

MRI-negative refractory partial epilepsy: role for diffusion tensor imaging in high field MRI.

PubMed

Chen, Qin; Lui, Su; Li, Chun-Xiao; Jiang, Li-Jun; Ou-Yang, Luo; Tang, He-Han; Shang, Hui-Fang; Huang, Xiao-Qi; Gong, Qi-Yong; Zhou, Dong

2008-07-01

Our aim is to use the high field MR scanner (3T) to verify whether diffusion tensor imaging (DTI) could help in locating the epileptogenic zone in patients with MRI-negative refractory partial epilepsy. Fifteen patients with refractory partial epilepsy who had normal conventional MRI, and 40 healthy volunteers were recruited for the study. DTI was performed on a 3T MR scanner, individual maps of mean diffusivity (MD) and fractional anisotropy (FA) were calculated, and Voxel-Based Analysis (VBA) was performed for individual comparison between patients and controls. Voxel-based analysis revealed significant MD increase in variant regions in 13 patients. The electroclinical seizure localization was concurred to seven patients. No patient exhibited regions of significant decreased MD. Regions of significant reduced FA were observed in five patients, with two of these concurring with electroclinical seizure localization. Two patients had regions of significant increase in FA, which were distinct from electroclinical seizure localization. Our study's results revealed that DTI is a responsive neuroradiologic technique that provides information about the epileptogenic areas in patients with MRI-negative refractory partial epilepsy. This technique may also helpful in pre-surgical evaluation.

Epileptic negative drop attacks in atypical benign partial epilepsy: a neurophysiological study.

PubMed

Hirano, Yoshiko; Oguni, Hirokazu; Osawa, Makiko

2009-03-01

We conducted a computer-assisted polygraphic analysis of drop attacks in a child with atypical benign partial epilepsy (ABPE) to investigate neurophysiological characteristics. The patient was a six-year two-month-old girl, who had started to have focal motor seizures, later combined with daily epileptic negative myoclonus (ENM) and drop attacks, causing multiple injuries. We studied episodes of ENM and drop attacks using video-polygraphic and computer-assisted back-averaging analysis. A total of 12 ENM episodes, seven involving the left arm (ENMlt) and five involving both arms (ENMbil), and five drop attacks were captured for analysis. All episodes were time-locked to spike-and-wave complexes (SWC) arising from both centro-temporo-parietal (CTP) areas. The latency between the onset of SWC and ENMlt, ENMbil, and drop attacks reached 68 ms, 42 ms, and 8 ms, respectively. The height of the spike as well as the slow-wave component of SWC for drop attacks were significantly larger than that for both ENMlt and ENMbil (p < 0.05). Drop attacks were considered to be epileptic negative myoclonus involving not only upper proximal but also axial muscles, causing the body to fall. Thus, drop attacks in ABPE are considered to be epileptic negative drop attacks arising from bilateral CTP foci and differ from drop attacks of a generalized origin seen in Lennox-Gastaut syndrome and myoclonic-astatic epilepsy.

Persistent Interictal Musical Hallucination in a Patient With Mesial Temporal Sclerosis-Related Epilepsy: First Case Report and Etiopathological Hypothesis.

PubMed

Borelli, Paolo; Vedovello, Marcella; Braga, Massimiliano; Pederzoli, Massimo; Beretta, Sandro

2016-12-01

Musical hallucination is a disorder of complex sound processing of instrumental music, songs, choirs, chants, etc. The underlying pathologies include moderate to severe acquired hearing loss (the auditory equivalent of Charles Bonnet syndrome), psychiatric illnesses (depression, schizophrenia), drug intoxication (benzodiazepines, salicylate, pentoxifylline, propranolol), traumatic lesions along the acoustic pathways, and epilepsy. The hallucinations are most likely to begin late in life; 70% of patients are women. Musical hallucination has no known specific therapy. Treating the underlying cause is the most effective approach; neuroleptic and antidepressant medications have only rarely succeeded.Musical hallucination in epilepsy typically presents as simple partial seizures originating in the lateral temporal cortex. To our knowledge, no formal report of musical hallucination in the interictal state has been published before. In contrast, other interictal psychotic features are a relatively common complication, especially in patients with long-standing drug-resistant epilepsy.We describe a 62-year-old woman with a long history of mesial temporal lobe epilepsy whose musical hallucination was solely interictal. We speculate on the possible link between temporal epilepsy and her hallucination. We hypothesize that, as a result of her epileptic activity-induced damage, an imbalance developed between the excitatory and inhibitory projections connecting the mesial temporal cortex to the other auditory structures. These structures may have generated hyperactivity in the lateral temporal cortex through a "release" mechanism that eventually resulted in musical hallucination.

Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

PubMed

Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

2018-04-19

Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

Perampanel: a new add-on treatment for epilepsy.

PubMed

2013-02-01

Perampanel (Fycompa - Eisai) is a new antiepileptic drug marketed in the EU. It is licensed for use as adjunctive treatment of partial-onset seizuresi with or without secondarily generalised seizures in patients with epilepsy aged 12 years and older.2 Here we discuss the place of perampanel in the treatment of epilepsy.

Eslicarbazepine acetate: an update on efficacy and safety in epilepsy.

PubMed

Verrotti, Alberto; Loiacono, Giulia; Rossi, Alessandra; Zaccara, Gaetano

2014-01-01

Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

Scn2a deletion improves survival and brain-heart dynamics in the Kcna1-null mouse model of sudden unexpected death in epilepsy (SUDEP).

PubMed

Mishra, Vikas; Karumuri, Bharat K; Gautier, Nicole M; Liu, Rui; Hutson, Timothy N; Vanhoof-Villalba, Stephanie L; Vlachos, Ioannis; Iasemidis, Leonidas; Glasscock, Edward

2017-06-01

People with epilepsy have greatly increased probability of premature mortality due to sudden unexpected death in epilepsy (SUDEP). Identifying which patients are most at risk of SUDEP is hindered by a complex genetic etiology, incomplete understanding of the underlying pathophysiology and lack of prognostic biomarkers. Here we evaluated heterozygous Scn2a gene deletion (Scn2a+/-) as a protective genetic modifier in the Kcna1 knockout mouse (Kcna1-/-) model of SUDEP, while searching for biomarkers of SUDEP risk embedded in electroencephalography (EEG) and electrocardiography (ECG) recordings. The human epilepsy gene Kcna1 encodes voltage-gated Kv1.1 potassium channels that act to dampen neuronal excitability whereas Scn2a encodes voltage-gated Nav1.2 sodium channels important for action potential initiation and conduction. SUDEP-prone Kcna1-/- mice with partial genetic ablation of Nav1.2 channels (i.e. Scn2a+/-; Kcna1-/-) exhibited a two-fold increase in survival. Classical analysis of EEG and ECG recordings separately showed significantly decreased seizure durations in Scn2a+/-; Kcna1-/- mice compared with Kcna1-/- mice, without substantial modification of cardiac abnormalities. Novel analysis of the EEG and ECG together revealed a significant reduction in EEG-ECG association in Kcna1-/- mice compared with wild types, which was partially restored in Scn2a+/-; Kcna1-/- mice. The degree of EEG-ECG association was also proportional to the survival rate of mice across genotypes. These results show that Scn2a gene deletion acts as protective genetic modifier of SUDEP and suggest measures of brain-heart association as potential indices of SUDEP susceptibility. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

PubMed

Okazaki, Mitsutoshi; Adachi, Naoto; Akanuma, Nozomi; Hara, Koichiro; Ito, Masumi; Kato, Masaaki; Onuma, Teiichi

2014-11-01

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

New insights into the clinical management of partial epilepsies.

PubMed

Hirsch, E; de Saint-Martin, A; Arzimanoglou, A

2000-01-01

The diagnosis, treatment, and prognosis of seizure disorders depend on the correct identification of epileptic syndromes. Partial epilepsies are heterogeneous and can be divided into idiopathic, cryptogenic, and symptomatic epilepsies. The most common of the idiopathic localization-related epilepsies is benign epilepsy with rolandic or centrotemporal spikes (BECTS). Seizures remain rare and the use of antiepileptic drug (AED) treatment in all patients does not appear justified. Children who present with some of the electroclinical characteristics of BECTS may also display severe unusual neurologic, neuropsychological, or atypical symptoms. In some cases, carbamazepine has been implicated as a triggering factor. Primary reading epilepsy and idiopathic occipital lobe epilepsies with photosensitivity are examples of an overlap between idiopathic localization-related and generalized epilepsies and respond well to sodium valproate. Autosomal dominant nocturnal frontal lobe epilepsy and benign familial infantile convulsions are recently described syndromes, differing in several ways from classical idiopathic localization-related epileptic syndromes. In cryptogenic or symptomatic epilepsy, the topography of the epileptogenic zone might influence drug efficacy. An individualized approach to AED selection, tailored to each patient's needs, should be used. Resistance of seizures to antiepileptic therapy may be due to diagnostic and/or treatment error or may be the result of noncompliance. Increasing the dosage, discontinuation or replacement of a drug, or addition of a second drug is indicated in truly resistant cases. The use of more than two AEDs rarely optimizes seizure control, and in some cases reduction of treatment may improve seizure control while lessening side effects. EEG-video assessment of patients with refractory epilepsy is important. Indications for and timing of epilepsy surgery should be reconsidered. Surgical therapy should probably be used more often and earlier than it is at present.

Cognitive and psychosocial effects of oxcarbazepine monotherapy in newly diagnosed partial epilepsy.

PubMed

Kim, Daeyoung; Seo, Ji-Hye; Joo, Eun Yeon; Lee, Hyang Woon; Shin, Won Chul; Hong, Seung Bong

2014-01-01

The aim of this study was to assess the effects of oxcarbazepine (OXC) on cognition and psychosocial difficulties in patients with new-onset partial epilepsy. Cognitive and psychosocial assessments were performed before and after 6 to 12 months of OXC monotherapy in 52 drug-naive patients (25 women; mean age, 31.1 years; SD, 12.1 years). Cognitive functions were evaluated with well-structured and validated tools. Mood, psychological distress, subjective handicap, and quality of life were also evaluated. Differences between baseline and after-treatment evaluation were compared and adjusted for possible confounders such as age, sex, seizure control, duration of epilepsy, assessment interval, and epileptogenic region. Mean assessment interval was 231.8 (range, 182-348) days, and mean (SD) OXC dose at retest was 693.8 (208.9) mg. The OXC was found to have no significant adverse effect on cognition. Furthermore, OXC monotherapy was not found to affect psychosocial difficulties, including psychological distress and subjective handicap. The results suggest that OXC monotherapy could be used to treat newly diagnosed partial epilepsy without adversely affecting cognitive and psychosocial functions.

Vagus nerve stimulation therapy in partial epilepsy: a review.

PubMed

Panebianco, Mariangela; Zavanone, Chiara; Dupont, Sophie; Restivo, Domenico A; Pavone, Antonino

2016-09-01

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

Prevalence of Psychopathology in Childhood Epilepsy: Categorical and Dimensional Measures

ERIC Educational Resources Information Center

Dunn, David W.; Austin, Joan K.; Perkins, Susan M.

2009-01-01

Few studies have utilized both categorical and dimensional measures of psychopathology in children with epilepsy. We evaluated 173 children (88 males, 85 females; mean age 11.7y [SD 1.8]; range 9-14y) who had epilepsy (generalized 36%, partial 61%) for at least 6 months. The primary caregiver completed a dimensional measure, the Child Behavior…

Epilepsy surgery in the elderly: an unusual case of a 75-year-old man with recurrent status epilepticus.

PubMed

Tellez-Zenteno, Jose F; Sadanand, Venkatraman; Riesberry, Martha; Robinson, Christopher A; Ogieglo, Lissa; Masiowski, Paul; Vrbancic, Mirna

2009-06-01

Epilepsy surgery is increasingly well-supported as an effective treatment for patients with intractable epilepsy. It is most often performed on younger patients and the safety and efficacy of epilepsy surgery in elderly patients are not frequently described. We report a case of a 75-year-old right-handed man who underwent a left fronto-temporal craniotomy for resection of a suprasellar meningioma in 2002. Immediately following hospital discharge, he began to experience complex partial seizures. He continued to have frequent seizures despite treatment with multiple combinations of antiepileptic medications. He presented with status epilepticus every two or three months, and required long periods of hospitalization on each occasion for post-ictal confusion and aphasia. Scalp EEG showed continuous spikes and polyspikes and persistent slowing in the left temporal area, as well as spikes in the left frontal area. EEG telemetry recorded multiple seizures, all with a clear focus in the left temporal area. MRI scan showed an area of encephalomalacia in the left temporal lobe, as well as post-surgical changes in the left frontal area. Neuropsychological testing showed bilateral memory impairment with no significant cognitive decline expected after unilateral temporal lobe resection. A left anteromesial temporal lobectomy was performed with intraoperative electrocorticography. Since surgery, the patient was not seizure-free (Engel class II-b), but had no further episodes of status epilepticus in one year and two months of follow-up. This is one of the oldest patients reported in the literature with epilepsy surgery and supports the possibility of epilepsy surgery in elderly patients for particular cases. In addition, few cases with such a malignant evolution of temporal lobe epilepsy have been described in this age group.

The relationship of seizure focus with depression, anxiety, and health-related quality of life in children and adolescents with epilepsy.

PubMed

Schraegle, William A; Titus, Jeffrey B

2017-03-01

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age=11.34, SD=3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Focal seizure symptoms in idiopathic generalized epilepsies.

PubMed

Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

2015-08-18

We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

Relationship between social competence and neurocognitive performance in children with epilepsy.

PubMed

Raud, Triin; Kaldoja, Mari-Liis; Kolk, Anneli

2015-11-01

Epilepsy may affect a child's social skills and social cognition. The purpose of the study was to examine associations between sociocognitive skills and neurocognitive performance in children with epilepsy. Thirty-five children with epilepsy between the ages of 7 and 12 years (25 with partial and 10 with generalized epilepsy) and 30 controls participated. Theory of Mind (ToM) tasks, Social Cognition Questionnaire proposed by Saltzman-Benaiah and Lalonde (2007), and Social Skills Rating System were used to assess social competence and sociocognitive skills. Neurocognitive performance was assessed using the NEPSY battery. Children with epilepsy demonstrated more difficulties in understanding false belief (p<.001) and intentional lying (p<.05) and exhibited more behavioral problems (p<.05). Notably, their social skills were at the same level as typically developing peers. Children with epilepsy performed significantly worse in attention, executive, verbal, and fine motor tasks (p<.05). We found positive correlations between the understanding of false belief and in executive (r=.6, p<.05), verbal (r=.45-.49, p<.05), and visuospatial skills (r=.34-.48, p<0.01). Children with generalized epilepsy had more problems in memory tasks (p<.05) and understanding of sarcasm (p<.05) compared with children with partial epilepsy. An age of onset over 9.1 years was positively associated with ToM skills (r=.42, p<.05). In conclusion, better ToM in children with better executive functions, and language and visuospatial skills was revealed. The type of epilepsy and age of onset significantly affected ToM skills. Copyright © 2015 Elsevier Inc. All rights reserved.

Termination patterns of complex partial seizures: An intracranial EEG study.

PubMed

Afra, Pegah; Jouny, Christopher C; Bergey, Gregory K

2015-11-01

While seizure onset patterns have been the subject of many reports, there have been few studies of seizure termination. In this study we report the incidence of synchronous and asynchronous termination patterns of partial seizures recorded with intracranial arrays. Data were collected from patients with intractable complex partial seizures undergoing presurgical evaluations with intracranial electrodes. Patients with seizures originating from mesial temporal and neocortical regions were grouped into three groups based on patterns of seizure termination: synchronous only (So), asynchronous only (Ao), or mixed (S/A, with both synchronous and asynchronous termination patterns). 88% of the patients in the MT group had seizures with a synchronous pattern of termination exclusively (38%) or mixed (50%). 82% of the NC group had seizures with synchronous pattern of termination exclusively (52%) or mixed (30%). In the NC group, there was a significant difference of the range of seizure durations between So and Ao groups, with Ao exhibiting higher variability. Seizures with synchronous termination had low variability in both groups. Synchronous seizure termination is a common pattern for complex partials seizures of both mesial temporal or neocortical onset. This may reflect stereotyped network behavior or dynamics at the seizure focus. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy.

PubMed

Frost, J J; Mayberg, H S; Fisher, R S; Douglass, K H; Dannals, R F; Links, J M; Wilson, A A; Ravert, H T; Rosenbaum, A E; Snyder, S H

1988-03-01

Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.

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.

Alterations in the contents of consciousness in partial epileptic seizures.

PubMed

Johanson, Mirja; Valli, Katja; Revonsuo, Antti; Chaplin, John E; Wedlund, Jan-Eric

2008-08-01

Epilepsy research suffers from a deficiency of systematic studies concerning the phenomenology of the contents of consciousness during seizures, partially because of the lack of suitable research methods. The Phenomenology of Consciousness Inventory (PCI), a standardized, valid, and reliable questionnaire, was used here to study which dimensions of the contents of consciousness are distorted during partial epileptic seizures compared with baseline. Further, the similarity of the altered pattern of subjective experiences across recurring seizures was also explored. Our results indicate that patients with epilepsy report alterations on most dimensions of the contents of consciousness in conjunction with seizures, but individual seizure experiences remain similar from one seizure to another. The PCI was found suitable for the assessment of subjective experiences during epileptic seizures and could be a valuable tool in providing new information about phenomenal consciousness in epilepsy in both the research and clinical settings.

Protective Effect of Resveratrol on the Brain in a Rat Model of Epilepsy.

PubMed

Li, Zhen; You, Zhuyan; Li, Min; Pang, Liang; Cheng, Juan; Wang, Liecheng

2017-06-01

Accumulating evidence has suggested resveratrol as a promising drug candidate for the treatment of epilepsy. To validate this, we tested the protective effect of resveratrol on a kainic acid (KA)-induced epilepsy model in rats and investigated the underlying mechanism. We found that acute resveratrol application partially inhibited evoked epileptiform discharges in the hippocampal CA1 region. During acute, silent and chronic phases of epilepsy, the expression of hippocampal kainate glutamate receptor (GluK2) and the GABA A receptor alpha1 subunit (GABA A R-alpha1) was up-regulated and down-regulated, respectively. Resveratrol reversed these effects and induced an antiepileptic effect. Furthermore, in the chronic phase, resveratrol treatment inhibited the KA-induced increased glutamate/GABA ratio in the hippocampus. The antiepileptic effects of resveratrol may be partially attributed to the reduction of glutamate-induced excitotoxicity and the enhancement in GABAergic inhibition.

The role of executive functioning in memory performance in pediatric focal epilepsy

PubMed Central

Sepeta, Leigh N.; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D.; Berl, Madison M.

2016-01-01

Objective Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Methods Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (WASI/DAS), as well as visual (CMS Dot Locations) and verbal episodic memory (WRAML Story Memory and CVLT-C). Executive functioning was measured directly (WISC-IV Digit Span Backward; CELF-IV Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function (BRIEF)). Results Children with focal epilepsy had lower delayed free recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = .12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = .03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = .08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extra-temporal, frontal vs. extra-frontal). Significance Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. PMID:28111742

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China

PubMed Central

Zhu, Fei; Lang, Sen-Yang; Wang, Xiang-Qing; Shi, Xiao-Bing; Ma, Yun-Feng; Zhang, Xu; Chen, Ya-Nan; Zhang, Jia-Tang

2015-01-01

Background: It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy. Methods: This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated. Results: A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64–44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%). Conclusion: This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate. PMID:26608980

Distinguishing between direct and indirect directional couplings in large oscillator networks: Partial or non-partial phase analyses?

NASA Astrophysics Data System (ADS)

Rings, Thorsten; Lehnertz, Klaus

2016-09-01

We investigate the relative merit of phase-based methods for inferring directional couplings in complex networks of weakly interacting dynamical systems from multivariate time-series data. We compare the evolution map approach and its partialized extension to each other with respect to their ability to correctly infer the network topology in the presence of indirect directional couplings for various simulated experimental situations using coupled model systems. In addition, we investigate whether the partialized approach allows for additional or complementary indications of directional interactions in evolving epileptic brain networks using intracranial electroencephalographic recordings from an epilepsy patient. For such networks, both direct and indirect directional couplings can be expected, given the brain's connection structure and effects that may arise from limitations inherent to the recording technique. Our findings indicate that particularly in larger networks (number of nodes ≫10 ), the partialized approach does not provide information about directional couplings extending the information gained with the evolution map approach.

Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy

PubMed Central

Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia

2013-01-01

Objective: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. Methods: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. Results: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%–59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%–64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ∼7% from 1 to 5 years postimplantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0–11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. Recommendations: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. PMID:23986299

Lamotrigine add-on for drug-resistant partial epilepsy.

PubMed

Ramaratnam, S; Marson, A G; Baker, G A

2001-01-01

Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (January 1966 to April 2001) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1.61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available precludes any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

Lamotrigine add-on for drug-resistant partial epilepsy.

PubMed

Ramaratnam, S; Marson, A G; Baker, G A

2000-01-01

Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available preclude any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

Dental care in patients with epilepsy: a survey of 82 patients and their attending dentists and neurologists in southern Germany.

PubMed

Schöpper, Malin; Ludolph, Albert C; Fauser, Susanne

2016-12-01

The current study assessed the knowledge and attitudes of dentists and neurologists, and of their patients with epilepsy, in the catchment area of an outpatient clinic for epilepsy in southern Germany. One-hundred patients with epilepsy were asked to complete questionnaires about their dental treatment. Attitudes of their attending dentists and neurologists were also assessed. Patients with epilepsy: The questionnaires were returned by 82% of patients. Of these, 84% regularly (once or twice a year) sought out a dentist, 79% reported their epilepsy to the dentist, 6% were refused treatment by a dentist because of their epilepsy, 10% had already experienced a seizure while at a dental office and 52% wished for more detailed information pretreatment. Dentists: Although 97% treated patients with epilepsy, 21% believed that their equipment was inappropriate for treating a patient experiencing seizures. The majority were not familiar with interactions between antibiotics/analgetics and anti-epileptic drugs. Short-term general anaesthesia was preferred for critical patients by 70% of dentists, 70% recommended dental ceramic for prosthetic reconstruction of anterior teeth and 64% would not recommend use of a removable denture. Neurologists: Sixty-two per cent were asked for advice by their patients, 71% knew about particular risks and interactions between antibiotics/analgetics and anti-epileptic drugs, 8% would stop valproic acid before extensive dental intervention and 92% recommended general anaesthesia in critical patients (uncooperative patients, patients with learning difficulties, and patients with frequent generalised tonic-clonic or complex partial seizures). In general, patients were satisfied with their dental treatment. Regarding the clinician's role, however, dentists need to know more with respect to treating patients with seizures. Beyond that, it would be desirable for neurologists to take more time to answer their patients' questions regarding dental care. © 2016 FDI World Dental Federation.

A predictive risk model for medical intractability in epilepsy.

PubMed

Huang, Lisu; Li, Shi; He, Dake; Bao, Weiqun; Li, Ling

2014-08-01

This study aimed to investigate early predictors (6 months after diagnosis) of medical intractability in epilepsy. All children <12 years of age having two or more unprovoked seizures 24 h apart at Xinhua Hospital between 1992 and 2006 were included. Medical intractability was defined as failure, due to lack of seizure control, of more than 2 antiepileptic drugs at maximum tolerated doses, with an average of more than 1 seizure per month for 24 months and no more than 3 consecutive months of seizure freedom during this interval. Univariate and multivariate logistic regression models were performed to determine the risk factors for developing medical intractability. Receiver operating characteristic curve was applied to fit the best compounded predictive model. A total of 649 patients were identified, out of which 119 (18%) met the study definition of intractable epilepsy at 2 years after diagnosis, and the rate of intractable epilepsy in patients with idiopathic syndromes was 12%. Multivariate logistic regression analysis revealed that neurodevelopmental delay, symptomatic etiology, partial seizures, and more than 10 seizures before diagnosis were significant and independent risk factors for intractable epilepsy. The best model to predict medical intractability in epilepsy comprised neurological physical abnormality, age at onset of epilepsy under 1 year, more than 10 seizures before diagnosis, and partial epilepsy, and the area under receiver operating characteristic curve was 0.7797. This model also fitted best in patients with idiopathic syndromes. A predictive model of medically intractable epilepsy composed of only four characteristics is established. This model is comparatively accurate and simple to apply clinically. Copyright © 2014 Elsevier Inc. All rights reserved.

Lacosamide in refractory mixed pediatric epilepsy: a prospective add-on study.

PubMed

Rastogi, Reena Gogia; Ng, Yu-Tze

2012-04-01

Lacosamide is a new antiepileptic drug that is currently approved by the US Food and Drug Administration (FDA) for adults 17 years or older for partial-onset seizures. The authors reviewed 21 pediatric patients (<17 years) with various seizure types who were started on oral lacosamide as part of a prospective add-on study as adjunctive therapy for refractory epilepsy. Five patients were excluded due to less than 3 months of meaningful follow-up. Maintenance dosages used ranged from 2.4 to 19.4 mg/kg/d. Eight of 16 (50%) patients had greater than 50% reduction in seizure frequency with adjunctive lacosamide therapy. Eight (50%) patients had generalized epilepsy including 4 with Lennox-Gastaut syndrome. Lacosamide was effective therapy for most seizure types but was particularly effective for partial-onset seizures. Lacosamide was effective in treating 5 of 8 (62.5%) localization-related epilepsies but only 2 of 8 (25%) generalized epilepsies, both Lennox-Gastaut syndrome patients with greater than 90% seizure reduction. None of these very refractory patients remained seizure free.

Self-concept and gender effects in Korean adolescents with epilepsy.

PubMed

Lee, Sang-Ahm; Choi, Eun-Ju; Kwon, Soonhak; Eom, Soyong

2016-08-01

We aimed to determine whether adolescents with epilepsy (AWE) have a compromised self-concept, whether a lower self-concept is related to mental health, and whether there are sex differences in self-concept in AWE. A total of 179 AWE and 259 control adolescents without epilepsy participated in this cross-sectional, multicenter study. Self-concept was measured using the Harter's Self-Perception Profile for Children. Depressive symptoms and anxiety were assessed by the Hospital Anxiety Depression Scale (HADS). A group-by-sex interaction was evaluated using an analysis of covariance controlling for age. Adolescents with epilepsy had a lower level of self-concept, especially in domains of behavioral conduct (partial eta(2): 0.257) and social acceptance (partial eta(2): 0.116), than controls (p<0.05). The level of self-concept did not differ by sex in the group with epilepsy. A group-by-sex interaction effect was found on social acceptance (p=0.042). Unlike the control group, age was not correlated with self-concept in AWE. Physical appearance was negatively correlated with HADS-anxiety scores (r=-0.291, p<0.01) but only in girls with epilepsy. Epilepsy duration was correlated with social acceptance in boys (r=0.211, p<0.05) and physical appearance in girls (r=-0.249, p<0.05). Adolescents with epilepsy had a lower level of self-concept, especially in the domains of behavioral conduct and social acceptance, than controls. Sex differences in self-concept were identified in the control group but not in the group with epilepsy. Physical appearance was negatively correlated with anxiety in girls with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of executive functioning in memory performance in pediatric focal epilepsy.

PubMed

Sepeta, Leigh N; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D; Berl, Madison M

2017-02-01

Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η 2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η 2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η 2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2012-06-13

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people are not well controlled by a single antiepileptic drug and usually require treatment with a combination of two or more antiepileptic drugs. In recent years, many newer antiepileptic drugs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (1 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library, 2012) and MEDLINE (1 May 2012). We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. There were no language restrictions. Randomized controlled add-on trials comparing losigamone with placebo for partial epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RR) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 patients were eligible for inclusion. Both trials assessed losigamone 1200 or 1500 mg/d as an add-on therapy for partial epilepsy. One trial was assessed as being of good methodologic quality while the other was of uncertain quality. For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.75; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/d) is associated with a greater reduction in seizure frequency than lower doses, but is also associated with more dropouts due to adverse events. The results of this review showed losigamone can reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed.

Partial monosomy Xq(Xq23 --> qter) and trisomy 4p(4p15.33 --> pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features.

PubMed

Bartocci, Arnaldo; Striano, Pasquale; Mancardi, Maria Margherita; Fichera, Marco; Castiglia, Lucia; Galesi, Ornella; Michelucci, Roberto; Elia, Maurizio

2008-06-01

Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.

Neonatal episodic hypoglycemia: a finding of valproic acid withdrawal.

PubMed

Çoban, Dilek; Kurtoğlu, Selim; Akın, Mustafa Ali; Akçakuş, Mustafa; Güneş, Tamer

2010-01-01

The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VPA and PH. The mother was diagnosed as having complex partial epilepsy and was treated with PH (200 mg/day) and VPA (600 mg/day). The offspring developed jitteriness on the second day of life. The infant was hypoglycemic (32 mg/dl). These findings were accepted as withdrawal symptoms, since serum levels of VPA and PH were 37.8 μg/ml (50-100 μg/ml) and 6.37 μg/dl (10-20 μg/ml), respectively. Measurement of blood glucose is important and should be carefully monitored in infants exposed to antiepileptics in utero.

Imaging DC MEG Fields Associated with Epileptic Onset

NASA Astrophysics Data System (ADS)

Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

2004-10-01

Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

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.

Familial mesial temporal lobe epilepsy maps to chromosome 4q13.2-q21.3.

PubMed

Hedera, P; Blair, M A; Andermann, E; Andermann, F; D'Agostino, D; Taylor, K A; Chahine, L; Pandolfo, M; Bradford, Y; Haines, J L; Abou-Khalil, B

2007-06-12

To report results of linkage analysis in a large family with autosomal dominant (AD) familial mesial temporal lobe epilepsy (FMTLE). Although FMTLE is a heterogeneous syndrome, one important subgroup is characterized by a relatively benign course, absence of antecedent febrile seizures, and absence of hippocampal sclerosis. These patients have predominantly simple partial seizures (SPS) and infrequent complex partial seizures (CPS), and intense and frequent déjà vu phenomenon may be the only manifestation of this epilepsy syndrome. No linkage has been described in this form of FMTLE. We identified a four-generation kindred with several affected members meeting criteria for FMTLE and enrolled 21 individuals who gave informed consent. Every individual was personally interviewed and examined; EEG and MRI studies were performed on three affected subjects. DNA was extracted from every enrolled individual. We performed a genome-wide search using an 8 cM panel and fine mapping was performed in the regions with a multipoint lod score >1. We sequenced the highest priority candidate genes. Inheritance was consistent with AD mode with reduced penetrance. Eleven individuals were classified as affected with FMTLE and we also identified two living asymptomatic individuals who had affected offspring. Seizure semiologies included predominantly SPS with déjà vu feeling, infrequent CPS, and rare secondarily generalized tonic-clonic seizures. No structural abnormalities, including hippocampal sclerosis, were detected on MRI performed on three individuals. Genetic analysis detected a group of markers with lod score >3 on chromosome 4q13.2-q21.3 spanning a 7 cM region. No ion channel genes are predicted to be localized within this locus. We sequenced all coding exons of sodium bicarbonate cotransporter (SLC4A) gene, which plays an important role in tissue excitability, and cyclin I (CCNI), because of its role in the cell migration and possibility of subtle cortical abnormalities. No disease-causing mutations were identified in these genes. We report identification of a genetic locus for familial mesial temporal lobe epilepsy. The identification of a disease-causing gene will contribute to our understanding of the pathogenesis of temporal lobe epilepsies.

The concept of symptomatic epilepsy and the complexities of assigning cause in epilepsy.

PubMed

Shorvon, Simon

2014-03-01

The concept of symptomatic epilepsy and the difficulties in assigning cause in epilepsy are described. A historical review is given, emphasizing aspects of the history which are relevant today. The historical review is divided into three approximately semicentenial periods (1860-1910, 1910-1960, 1960-present). A definition of symptomatic epilepsy and this is followed by listing of causes of symptomatic epilepsy. The fact that not all the causes of idiopathic epilepsy are genetic is discussed. A category of provoked epilepsy is proposed. The complexities in assigning cause include the following: the multifactorial nature of epilepsy, the distinction between remote and proximate causes, the role of nongenetic factors in idiopathic epilepsy, the role of investigation in determining the range of causes, the fact that not all symptomatic epilepsy is acquired, the nosological position of provoked epilepsy and the view of epilepsy as a process, and the differentiation of new-onset and established epilepsy. The newly proposed ILAE classification of epilepsy and its changes in terminologies and the difficulties in the concept of acute symptomatic epilepsy are discussed, including the inconsistencies and gray areas and the distinction between idiopathic, symptomatic, and provoked epilepsies. Points to be considered in future work are listed. Copyright © 2013 Elsevier Inc. All rights reserved.

Evidence-Based Guideline Update: Vagus Nerve Stimulation for the Treatment of Epilepsy

PubMed Central

Morris, George L.; Gloss, David; Buchhalter, Jeffrey; Mack, Kenneth J.; Nickels, Katherine; Harden, Cynthia

2013-01-01

OBJECTIVE: To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. METHODS: We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. RESULTS: VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%–59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%–64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥50% seizure frequency reduction rates of ~7% from 1 to 5 years postim-plantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0–11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. RECOMMENDATIONS: VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation. Neurology® 2013;81:1–7 PMID:24348133

Heart rate changes in partial seizures: analysis of influencing factors among refractory patients

PubMed Central

2014-01-01

Background We analyzed the frequency of heart rate (HR) changes related to seizures, and we sought to identify the influencing factors of these changes during partial seizures, to summarize the regularity of the HR changes and gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. To date, detailed information on influencing factors of HR changes related to seizures by multiple linear regression analysis remains scarce. Methods Using video-electroencephalograph (EEG)-electrocardiograph (ECG) recordings, we retrospectively assessed the changes in the HR of 81 patients during a total of 181 seizures, including 27 simple partial seizures (SPS), 110 complex partial seizures (CPS) and 44 complex partial seizures secondarily generalized (CPS-G). The epileptogenic focus and the seizure type, age, gender, and sleep/wakefulness state of each patient were evaluated during and after the seizure onset. The HR changes were evaluated in the stage of epilepsy as time varies. Results Of the 181 seizures from 81 patients with ictal ECGs, 152 seizures (83.98%) from 74 patients were accompanied by ictal tachycardia (IT). And only 1 patient was accompanied by ictal bradycardia (IB). A patient has both IT and IB. We observed that HR difference was independently correlated with side, type and sleep/wakefulness state. In this analysis, the HR changes were related to the side, gender, seizure type, and sleep/wakefulness state. Right focus, male, sleep, and CPS-G showed more significant increases than that were observed in left, female, wakefulness, SPS and CPS. HR increases rapidly within 10 seconds before seizure onset and ictus, and typically slows to normal with seizure offset. Conclusion CPS-G, sleep and right focus led to higher ictal HR. The HR in the stage of epilepsy has regularly been observed to change to become time-varying. The risk factors of ictal HR need to be controlled along with sleep, CPS-G and right focus. Our study first explains that the HR in seizures has a regular evolution varying with time. Our study might help to further clarify the basic mechanisms of interactions between heart and brain, making seizure detection and closed-loop systems a possible therapeutic alternative in refractory patients. PMID:24950859

Benign childhood epilepsy with occipital paroxysms: neuropsychological findings.

PubMed

Germanò, Eva; Gagliano, Antonella; Magazù, Angela; Sferro, Caterina; Calarese, Tiziana; Mannarino, Erminia; Calamoneri, Filippo

2005-05-01

Benign childhood epilepsy with occipital paroxysms is classified among childhood benign partial epilepsies. The absence of neurological and neuropsychological deficits has long been considered as a prerequisite for a diagnosis of benign childhood partial epilepsy. Much evidence has been reported in literature in the latest years suggesting a neuropsychological impairment in this type of epilepsy, particularly in the type with Rolandic paroxysms. The present work examines the neuropsychological profiles of a sample of subjects affected by the early-onset benign childhood occipital seizures (EBOS) described by Panayotopulos. The patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3 years) diagnosed as having EBOS. The patients were examined with a set of tests investigating neuropsychological functions: memory, attention, perceptive, motor, linguistic and academic (reading, writing, arithmetic) abilities. The same instruments have been given to a homogeneous control group as regards sex, age, level of education and socio-economic background. None of the subjects affected by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D. 8.9). Results show a widespread cognitive dysfunction in the context of a focal epileptogenic process in EBOS. In particular, children with EBOS show a significant occurrence of specific learning disabilities (SLD) and other subtle neuropsychological deficits. We found selective dysfunctions relating to perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory abilities (p<0.01), visual perception and visual-motor integration global abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01). The presence of cognitive dysfunctions in subjects with EBOS supports the hypothesis that epilepsy itself plays a role in the development of neuropsychological impairment. Supported by other studies that have documented subtle neuropsychological deficits in benign partial epilepsy, we stress the importance of reconsidering its supposed "cognitive benignity", particularly in occipital types.

Probability of detection of clinical seizures using heart rate changes.

PubMed

Osorio, Ivan; Manly, B F J

2015-08-01

Heart rate-based seizure detection is a viable complement or alternative to ECoG/EEG. This study investigates the role of various biological factors on the probability of clinical seizure detection using heart rate. Regression models were applied to 266 clinical seizures recorded from 72 subjects to investigate if factors such as age, gender, years with epilepsy, etiology, seizure site origin, seizure class, and data collection centers, among others, shape the probability of EKG-based seizure detection. Clinical seizure detection probability based on heart rate changes, is significantly (p<0.001) shaped by patients' age and gender, seizure class, and years with epilepsy. The probability of detecting clinical seizures (>0.8 in the majority of subjects) using heart rate is highest for complex partial seizures, increases with a patient's years with epilepsy, is lower for females than for males and is unrelated to the side of hemisphere origin. Clinical seizure detection probability using heart rate is multi-factorially dependent and sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the role that these factors play in shaping said probability will enhance its applicability and usefulness. Heart rate is a reliable and practical signal for extra-cerebral detection of clinical seizures originating from or spreading to central autonomic network structures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

How do we make models that are useful in understanding partial epilepsies?

PubMed

Prince, David A

2014-01-01

The goals of constructing epilepsy models are (1) to develop approaches to prophylaxis of epileptogenesis following cortical injury; (2) to devise selective treatments for established epilepsies based on underlying pathophysiological mechanisms; and (3) use of a disease (epilepsy) model to explore brain molecular, cellular and circuit properties. Modeling a particular epilepsy syndrome requires detailed knowledge of key clinical phenomenology and results of human experiments that can be addressed in critically designed laboratory protocols. Contributions to understanding mechanisms and treatment of neurological disorders has often come from research not focused on a specific disease-relevant issue. Much of the foundation for current research in epilepsy falls into this category. Too strict a definition of the relevance of an experimental model to progress in preventing or curing epilepsy may, in the long run, slow progress. Inadequate exploration of the experimental target and basic laboratory results in a given model can lead to a failed effort and false negative or positive results. Models should be chosen based on the specific issues to be addressed rather than on convenience of use. Multiple variables including maturational age, species and strain, lesion type, severity and location, latency from injury to experiment and genetic background will affect results. A number of key issues in clinical and basic research in partial epilepsies remain to be addressed including the mechanisms active during the latent period following injury, susceptibility factors that predispose to epileptogenesis, injury - induced adaptive versus maladaptive changes, mechanisms of pharmaco-resistance and strategies to deal with multiple pathophysiological processes occurring in parallel.

Illness perception in Chinese adults with epilepsy.

PubMed

Ji, Haixia; Zhang, Lei; Li, Lunlan; Gong, Guiping; Cao, Zhaolun; Zhang, Jianfeng; Zhou, Nong; Wang, Yu; Tu, Houmian; Wang, Kai

2016-12-01

Epilepsy is among the most common neurological disorders worldwide. Understanding the patient's subjective experience plays an important role in the treatment and rehabilitation of the patient. However, few studies are concerned about the illness perception of Chinese adults with epilepsy. 117 Chinese adults with epilepsy and 87 Chinese adults with chronic liver disease completed the Chinese version of the Revised Illness Perception Questionnaire (CIPQ-R). The Chinese epilepsy patients also completed the Social Support Rating Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ). A comparison about CIPQ-R score between the epilepsy group and chronic liver group was conducted using the independent sample t test. Partial correlation coefficients were calculated among the eight subscales of the CIPQ-R and its associated factors. Results for the CIPQ-R indicated that both the epilepsy patients and the chronic liver disease patients had a moderate belief in their personal control and treatment control over their disorder. Consistent with our hypothesis, patients with epilepsy and those with chronic liver disease perceived their respective disease similarly in terms of timeline and illness coherence. However, epilepsy patients had a higher negative emotional representations level than that we expected when compared to those of the patients suffering from chronic liver disease. Partial correlation analysis in Chinese epilepsy patients showed that the timeline acute/chronic dimension and emotional representations dimension were closely related to the other dimensions of illness perception. Moreover, the illness perception of the patients was significantly associated with social support, coping style, duration of epilepsy, seizure frequency, and the number of antiepileptic drugs. Chinese patients with epilepsy had limited understanding of the illness, and poor belief in personal control and treatment control. They had a negative emotional response to their illness, and feared of the effects on the patient or patient's family. Social support, coping style, duration of epilepsy, seizure frequency, and the number of antiepileptic drugs could affect the illness perception of these patients. Further studies should focus on how to improve patients' attitudes towards their disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Partial epilepsy and 47,XXX karyotype: report of four cases.

PubMed

Roubertie, Agathe; Humbertclaude, Véronique; Leydet, Julie; Lefort, Geneviève; Echenne, Bernard

2006-07-01

Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy. Although a specific electro-clinical pattern could not be defined, the epileptic phenotypes of these patients share many features; we suggest that the association 47,XXX/epilepsy/mental retardation may not be coincidental. This report also enlarges the clinical spectrum of the 47,XXX phenotype. Moreover, these observations highlight the critical role of chromosome X in epilepsy and mental retardation.

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.

Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy.

PubMed

Hisada, K; Morioka, T; Nishio, S; Yamamoto, T; Fukui, M

2001-12-01

To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single-dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE.

Reflex epilepsy and reflex seizures of the visual system: a clinical review.

PubMed

Zifkin, B G; Kasteleijn-Nolst Trenité, D

2000-09-01

Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.

Impaired consciousness in partial seizures is bimodally distributed

PubMed Central

Cunningham, Courtney; Chen, William C.; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P.; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T.

2014-01-01

Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale–Revised (n = 552 test administrations, 184 patients). Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures. PMID:24727311

Impaired consciousness in partial seizures is bimodally distributed.

PubMed

Cunningham, Courtney; Chen, William C; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T; Blumenfeld, Hal

2014-05-13

To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n = 552 test administrations, 184 patients). Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures.

DEPDC5 as a potential therapeutic target for epilepsy.

PubMed

Myers, Kenneth A; Scheffer, Ingrid E

2017-06-01

Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.

Seizures and epileptiform activity in the early stages of Alzheimer disease.

PubMed

Vossel, Keith A; Beagle, Alexander J; Rabinovici, Gil D; Shu, Huidy; Lee, Suzee E; Naasan, Georges; Hegde, Manu; Cornes, Susannah B; Henry, Maya L; Nelson, Alexandra B; Seeley, William W; Geschwind, Michael D; Gorno-Tempini, Maria L; Shih, Tina; Kirsch, Heidi E; Garcia, Paul A; Miller, Bruce L; Mucke, Lennart

2013-09-01

Epileptic activity associated with Alzheimer disease (AD) deserves increased attention because it has a harmful impact on these patients, can easily go unrecognized and untreated, and may reflect pathogenic processes that also contribute to other aspects of the illness. We report key features of AD-related seizures and epileptiform activity that are instructive for clinical practice and highlight similarities between AD and transgenic animal models of the disease. To describe common clinical characteristics and treatment outcomes of patients with amnestic mild cognitive impairment (aMCI) or early AD who also have epilepsy or subclinical epileptiform activity. Retrospective observational study from 2007 to 2012. SETTING Memory and Aging Center, University of California, San Francisco. We studied 54 patients with a diagnosis of aMCI plus epilepsy (n = 12), AD plus epilepsy (n = 35), and AD plus subclinical epileptiform activity (n = 7). Clinical and demographic data, electroencephalogram (EEG) readings, and treatment responses to antiepileptic medications. Patients with aMCI who had epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy (64.3 vs 71.1 years; P = .02). Patients with AD who had epilepsy presented with cognitive decline 5.5 years earlier than patients with AD who did not have epilepsy (64.8 vs 70.3 years; P = .001). Patients with AD who had subclinical epileptiform activity also had an early onset of cognitive decline (58.9 years). The timing of seizure onset in patients with aMCI and AD was nonuniform (P < .001), clustering near the onset of cognitive decline. Epilepsies were most often complex partial seizures (47%) and more than half were nonconvulsive (55%). Serial or extended EEG monitoring appeared to be more effective than routine EEG at detecting interictal and subclinical epileptiform activity. Epileptic foci were predominantly unilateral and temporal. Of the most commonly prescribed antiepileptics, treatment outcomes appeared to be better for lamotrigine and levetiracetam than for phenytoin. Common clinical features of patients with aMCI- or AD-associated epilepsy at our center included early age at onset of cognitive decline, early incidence of seizures in the disease course, unilateral temporal epileptic foci detected by serial/extended EEG, transient cognitive dysfunction, and good seizure control and tolerability with lamotrigine and levetiracetam. Careful identification and treatment of epilepsy in such patients may improve their clinical course.

The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies.

PubMed

Santos, Kleber; Palmini, Andre; Radziuk, Ana L; Rotert, Rosana; Bastos, Fernanda; Booij, Linda; Fernandes, Brisa S

2013-07-01

Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Familial temporal lobe epilepsy autosomal dominant inheritance in a large pedigree from southern Italy.

PubMed

Gambardella, A; Messina, D; Le Piane, E; Oliveri, R L; Annesi, G; Zappia, M; Andermann, E; Quattrone, A; Aguglia, U

2000-02-01

To further elucidate the inheritance pattern and range of phenotypic manifestations of benign familial temporal lobe epilepsy (FTLE), we report a large family recently identified in southern Italy. There were 8 patients (4 men), ranging in age from 31 to 68 years in three generations. One affected patient was deceased at the time of the study. Genealogical study strongly supported autosomal dominant inheritance with incomplete penetrance, as three unaffected individuals transmitted the disease. Clinical anticipation could not be assessed because of the ascertainment method. Male to male transmission occurred. Identifiable antecedents for seizures were present in only two patients, who had a simple febrile convulsion and a closed head trauma, respectively. Migraine was overrepresented in this family. Onset of seizures ranged from 17 to 52 years (mean: 27 years). All patients had weekly simple partial seizures suggestive of temporal origin with vegetative or experiential phenomena. Very rare partial complex seizures occurred in 6/7 patients. One had two generalized nocturnal seizures as well. Two had previously been misdiagnosed as having gastritis or panic attacks, and one had not been diagnosed. Interictal anteromesiotemporal spiking was seen in 5/7 patients, and occurred mostly during NREM sleep. Neurological examination, brain CT or MR scans were normal. Antiepileptic medication always controlled the seizures.

Neuropsychological benefits of computer-assisted cognitive rehabilitation (using FORAMENRehab program) in children with mild traumatic brain injury or partial epilepsy: A pilot study.

PubMed

Kaldoja, Mari-Liis; Saard, Marianne; Lange, Kirsi; Raud, Triin; Teeveer, Ott-Kaarel; Kolk, Anneli

2015-01-01

The number of children with different cognitive difficulties is constantly increasing. Still, too few evidence-based pediatric neurocognitive rehabilitation programs exist. The main aim of the study was to assess the efficiency and usability of computer-assisted FORAMENRehab program for training specific components of attention in children with mild traumatic brain injury (mTBI) and partial epilepsy (PE). The second aim was to specify short- and long-term effects of the intervention. Eight children between the ages of 9-12 years with attention impairment (3 with PE and 5 with mTBI) and 18 healthy controls participated. FORAMENRehab Attention software, adapted by the authors, was used for intervention. Strict intervention protocol consisting of patients completing 10 sessions over a 6-week-period to train four components of attention (sustaining, focusing, dividing, tracking) was designed and applied. Follow-up assessments were conducted after the end of the last training and 1.63 years later. After the intervention patients' sustained and complex attention improved. Long-term follow-up revealed continuing positive rehabilitation effects. 100% compliance suggested that the used method is attractive for children. These preliminary results of the pilot study give reason to presume that the method is effective in attention impairment remediation. However, more thorough research is needed.

Efficacy and tolerability of lacosamide as an adjunctive therapy in children with refractory partial epilepsy.

PubMed

Pasha, Ismail; Kamate, Mahesh; Didagi, Suresh K

2014-10-01

A unicentre, prospective study was performed to investigate the efficacy of lacosamide as adjunctive therapy in children with refractory partial epilepsy. The study was performed at a tertiary care hospital over a period of 30 months between November 2011 and May 2014. Seventy-nine children with refractory partial epilepsy (age 5-15 years) who had failed two or more antiepileptic drugs and in whom lacosamide was used as an add-on drug were enrolled. Lacosamide tablets were administered orally, at a dose of 25 mg for 1 week followed by 50 mg twice daily for the remaining period. Efficacy and tolerability evaluation was performed at every visit of titration, maintenance period (3 months), and two follow-up visits at monthly interval. Electrocardiogram and liver function tests were performed before enrollment and at the end of 3 months of lacosamide therapy. Patient's caregiver or investigator observed adverse events were recorded in a predesigned pro forma. A total of 79 patients with uncontrolled partial epilepsy screened from 531 epileptic children were enrolled, after they satisfied the inclusion and exclusion criteria. The mean age of children enrolled was 8.8 ± 3.1 years (range 5-15 years); 53 children (67.0%) were boys. Mean weight of the patients was 24.2 ± 9.8 kg. The mean age at the onset of seizures was 6.4 ± 3.5 years. The mean dose of lacosamide administered was 4.1 mg/kg. Three patients (3.8%) dropped out of the study, because of vomiting, aggressive behavior, and poor response, respectively. Of 76 patients (96.2%) entering the maintenance period, 35 patients (44.3%) were seizure free, 32 patients (40.6%) indicated ≥50% reduction in seizure frequency, 3 patients (3.8%) indicated 25-49% seizure reduction, and 9 patients (11.4%) either had no change in seizure frequency or experience increase in seizure frequency. Lacosamide is an effective add-on antiepileptic drug for children with refractory partial epilepsy and is well tolerated. Copyright © 2014 Elsevier Inc. All rights reserved.

New onset paediatric epilepsy in 1-5 years age group children--approach to management in a tertiary care centre with newer anti-epileptic levetiracetam.

PubMed

Barik, Kanai Lal; Paul, Uttam Kumar; Bhattacharyya, Anup Kumar; Adhikary, Amit; Agarwal, Gajanand; Rana, Kriti Sundar

2014-02-01

Epilepsy is a common paediatric neurologic disorder that is difficult to manage in a substantial portion of children, highlighting the continued need for more effective and better tolerated drugs. A multicentric study was conducted from August, 2011 to July, 2013 using levetiracetam (LEV) in newely diagnosed epilepsy in 122 young children of 1-5 years age group to find its role in practical scenario depending upon the knowledge from prior literature available. It has been demonstrated effective as adjunctive therapy as well as monotherapy for new-onset partial seizures and generalised tonic-clonic seizures (GTCS) but it acts better as adjunctive therapy than the monotherapy. When LEV was used as adjunctive therapy 15.4% children with partial seizure were seizure-free as compared to 11.12% in GTCS and when LEV was used as monotherapy 16.17% children with partial seizure were seizure-free as compared to 15.38% in GTCS. When LEV was used as add on therapy 16.67% children < 2 years were seizure-free as compared to 17.85% in > 2 years. When LEV was used as monotherapy 25.00% children < 2 years were seizure-free as compared to 18.18% > 2 years. So, it was found more efficacious in partial group of seizures than the GTCS variety. It also shows more efficacy in older age group (> 2 years) than the younger ones (< 2 years). Somnolence and behavioural changes were noted as ad- verse effects in a few cases. So, LEV is an important addition to the treatment of paediatric epilepsy.

Direct medical costs for partial refractory epilepsy in Mexico.

PubMed

García-Contreras, Fernando; Constantino-Casas, Patricia; Castro-Ríos, Angélica; Nevárez-Sida, Armando; Estrada Correa, Gloria del Carmen; Carlos Rivera, Fernando; Guzmán-Caniupan, Jorge; Torres-Arreola, Laura del Pilar; Contreras-Hernández, Iris; Mould-Quevedo, Joaquin; Garduño-Espinosa, Juan

2006-04-01

The aim was to determine the direct medical costs in patients with partial refractory epilepsy at the Mexican Institute of Social Security (IMSS) in Mexico. We carried out a multicenter, retrospective-cohort partial-economic evaluation study of partial refractory epilepsy (PRE) diagnosed patients and analyzed patient files from four secondary- and tertiary-level hospitals. PRE patients >12 years of age with two or more antiepileptic drugs and follow-up for at least 1 year were included. The perspective was institutional (IMSS). Only direct healthcare costs were considered, and the timeline was 1 year. Cost techniques were microcosting, average per-service cost, and per-day cost, all costs expressed in U.S. dollars (USD, 2004). We reviewed 813 files of PRE patients: 133 had a correct diagnosis, and only 72 met study inclusion criteria. Fifty eight percent were females, 64% were <35 years of age, 47% were students, in 73% maximum academic level achieved was high school, and 53% were single. Fifty one percent of cases experienced simple partial seizures and 94% had more than one monthly seizure. Annual healthcare cost of the 72 patients was 190,486 USD, ambulatory healthcare contributing 76% and hospital healthcare with 24%. Annual mean healthcare cost per PRE patient was 2,646 USD; time of disease evolution and severity of the patient's illness did not affect costs significantly.

Targeted Upregulation of FMRP Expression as an Approach to the Treatment of Fragile X Syndrome

DTIC Science & Technology

2015-08-01

form of autism, and a relatively common cause of epilepsy . The syndrome is caused by partial or complete silencing of the fragile X (FMR1) gene when...potential to correct ALL of the clinical domains of fragile X syndrome, including epilepsy -like activity observed for both those with FXS and carriers of...the FMR1 gene. 15. SUBJECT TERMS Fragile X, autism, FMR1, FXTAS, CGG repeat, epilepsy , seizures, FMRP, PTSD, premutation, iPSC, progenitor, calcium

Baseline Cognition, Behavior, and Motor Skills in Children with New-Onset, Idiopathic Epilepsy

ERIC Educational Resources Information Center

Bhise, Vikram V.; Burack, Gail D.; Mandelbaum, David E.

2010-01-01

Aim: Epilepsy is associated with difficulties in cognition and behavior in children. These problems have been attributed to genetics, ongoing seizures, psychosocial issues, underlying abnormality of the brain, and/or antiepileptic drugs. In a previous study, we found baseline cognitive differences between children with partial versus generalized…

Mutations and Deletions in PCDH19 Account for Various Familial or Isolated Epilepsies in Females

PubMed Central

Depienne, Christel; Trouillard, Oriane; Bouteiller, Delphine; Gourfinkel-An, Isabelle; Poirier, Karine; Rivier, François; Berquin, Patrick; Nabbout, Rima; Chaigne, Denys; Steschenko, Dominique; Gautier, Agnès; Hoffman-Zacharska, Dorota; Lannuzel, Annie; Lackmy-Port-Lis, Marilyn; Maurey, Hélène; Dusser, Anne; Bru, Marie; Gilbert-Dussardier, Brigitte; Roubertie, Agathe; Kaminska, Anna; Whalen, Sandra; Mignot, Cyril; Baulac, Stéphanie; Lesca, Gaetan; Arzimanoglou, Alexis; LeGuern, Eric

2011-01-01

Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation. © 2010 Wiley-Liss, Inc. PMID:21053371

Effects of Jasminum multiflorum leaf extract on rodent models of epilepsy, motor coordination and anxiety.

PubMed

Addae, Jonas I; Pingal, Ramish; Walkins, Kheston; Cruickshank, Renee; Youssef, Farid F; Nayak, Shivananda B

2017-03-01

Jasmine flowers and leaves are used extensively in folk medicine in different parts of the world to treat a variety of diseases. However, there are very few published reports on the neuropsychiatric effects of Jasmine extracts. Hence, the objectives of the present study were to examine the effects of an alcohol extract of Jasminum multiflorum leaves on topically-applied bicuculline (a model of acute simple partial epilepsy) and maximal electroshock (MES, a model of generalized tonic-clonic seizure) in male Sprague-Dawley rats. The objectives also included an examination of the anxiolytic properties of the extract using an elevated plus maze and the effect of the extract on motor coordination using a rotarod treadmill. Phytochemical analysis of the extract showed the presence of three flavonoids and four additional compounds belonging to the steroid, terpenoid, phenol or sugar classes of compounds. The Jasmine alcohol extract, diluted with water and given orally or intraperitoneally, reduced the number of bicuculline-induced epileptiform discharges in a dose-dependent manner. The extract did not cause a significant increase in the current needed to induce hind limb extension in MES experiments. The extract significantly affected motor coordination when injected at 500mg/kg but not at 200mg/kg. At the latter dose, the extract increased open-arm entries and duration in the elevated plus maze to a level comparable to that of diazepam at 2mg/kg. We conclude that Jasmine leaf extract has a beneficial effect against an animal model of acute partial complex epilepsy, and significant anxiolytic effect at a dose that does not affect motor co-ordination. Copyright © 2017 Elsevier B.V. All rights reserved.

Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3.

PubMed

Korenke, Georg-Christoph; Eggert, Marlene; Thiele, Holger; Nürnberg, Peter; Sander, Thomas; Steinlein, Ortrud K

2016-03-01

Mutations in NPRL3, one of three genes that encode proteins of the mTORC1-regulating GATOR1 complex, have recently been reported to cause cortical dysplasia with focal epilepsy. We have now analyzed a multiplex epilepsy family by whole exome sequencing and identified a frameshift mutation (NM_001077350.2; c.1522delG; p.E508Rfs*46) within exon 13 of NPRL3. This truncating mutation causes an epilepsy phenotype characterized by early childhood onset of mainly nocturnal frontal lobe epilepsy. The penetrance in our family was low (three affected out of six mutation carriers), compared to families with either ion channel- or DEPDC5-associated familial nocturnal frontal lobe epilepsy. The absence of apparent structural brain abnormalities suggests that mutations in NPRL3 are not necessarily associated with focal cortical dysplasia but might be able to cause epilepsy by different, yet unknown pathomechanisms. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation.

PubMed

Striano, P; Busolin, G; Santulli, L; Leonardi, E; Coppola, A; Vitiello, L; Rigon, L; Michelucci, R; Tosatto, S C E; Striano, S; Nobile, C

2011-03-29

Autosomal dominant lateral temporal epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the LGI1 gene have been reported in up to 50% of ADLTE pedigrees. We report a family with temporal lobe epilepsy characterized by psychic symptoms associated with a novel LGI1 mutation. All participants were personally interviewed and underwent neurologic examination and video-EEG recordings. LGI1 exons were sequenced by standard methods. Mutant cDNA was transfected into human embryonic kidney 293 cells; both cell lysates and media were analyzed by Western blot. In silico modeling of the Lgi1 protein EPTP domain was carried out using the structure of WD repeat protein and manually refined. Three affected family members were ascertained, 2 of whom had temporal epilepsy with psychic symptoms (déjà vu, fear) but no auditory or aphasic phenomena, while the third had complex partial seizures without any aura. In all patients, we found a novel LGI1 mutation, Arg407Cys, which did not hamper protein secretion in vitro. Mapping of the mutation on a 3-dimensional protein model showed that this mutation does not induce large structural rearrangements but could destabilize interactions of Lgi1 with target proteins. The Arg407Cys is the first mutation with no effect on Lgi1 protein secretion. The uncommon, isolated psychic symptoms associated with it suggests that ADLTE encompasses a wider range of auras of temporal origin than hitherto reported.

[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.

Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study.

PubMed

Harden, Cynthia L; Herzog, Andrew G; Nikolov, Blagovest G; Koppel, Barbara S; Christos, Paul J; Fowler, Kristen; Labar, Douglas R; Hauser, W Allen

2006-09-01

Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. Twenty-one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA. CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.

Losigamone add-on therapy for partial epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2015-12-10

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people are not well controlled by a single antiepileptic drug (AED) and usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for partial epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6). To investigate the efficacy and safety of losigamone when used as an add-on therapy for partial epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (16 February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 16 February 2015) and MEDLINE (Ovid, 1946 to 16 February 2015). We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for partial epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 patients, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for partial epilepsy. One trial was assessed as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show patients taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76; 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16; 95% CI 1.28 to 3.67). For the safety outcomes, results indicated the proportion of patients who experienced adverse events in the losigamone group was higher than the placebo group (RR 1.34; 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82; 99% CI 1.69 to 8.64). The proportion of patients achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events. The results of this review showed losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with partial epilepsy. However, trials included were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review.

Multisensory temporal function and EEG complexity in patients with epilepsy and psychogenic nonepileptic events.

PubMed

Noel, Jean-Paul; Kurela, LeAnne; Baum, Sarah H; Yu, Hong; Neimat, Joseph S; Gallagher, Martin J; Wallace, Mark

2017-05-01

Cognitive and perceptual comorbidities frequently accompany epilepsy and psychogenic nonepileptic events (PNEE). However, and despite the fact that perceptual function is built upon a multisensory foundation, little knowledge exists concerning multisensory function in these populations. Here, we characterized facets of multisensory processing abilities in patients with epilepsy and PNEE, and probed the relationship between individual resting-state EEG complexity and these psychophysical measures in each patient. We prospectively studied a cohort of patients with epilepsy (N=18) and PNEE (N=20) patients who were admitted to Vanderbilt's Epilepsy Monitoring Unit (EMU) and weaned off of anticonvulsant drugs. Unaffected age-matched persons staying with the patients in the EMU (N=15) were also recruited as controls. All participants performed two tests of multisensory function: an audio-visual simultaneity judgment and an audio-visual redundant target task. Further, in the cohort of patients with epilepsy and PNEE we quantified resting state EEG gamma power and complexity. Compared with both patients with epilepsy and control subjects, patients with PNEE exhibited significantly poorer acuity in audiovisual temporal function as evidenced in significantly larger temporal binding windows (i.e., they perceived larger stimulus asynchronies as being presented simultaneously). These differences appeared to be specific for temporal function, as there was no difference among the three groups in a non-temporally based measure of multisensory function - the redundant target task. Further, patients with PNEE exhibited more complex resting state EEG patterns as compared to their patients with epilepsy, and EEG complexity correlated with multisensory temporal performance on a subject-by-subject manner. Taken together, findings seem to indicate that patients with PNEE bind information from audition and vision over larger temporal intervals when compared with control subjects as well as patients with epilepsy. This difference in multisensory function appears to be specific to the temporal domain, and may be a contributing factor to the behavioral and perceptual alterations seen in this population. Published by Elsevier Inc.

The utility score of epilepsy with partial seizure measured by TTO, VAS, and EQ-5D in the general Korean population.

PubMed

Kang, Hee-Jin; Kang, Eunjeong; Jo, Min-Woo; Park, Eun-Ja; Yoon, Seonyoung; Lee, Eui-Kyung

2014-07-01

This study aimed to measure utilities, which are quantitative terms incorporating preferences, for various health states of epilepsy with partial seizure in the general population in South Korea. It also aimed to find socio-demographic characteristics associated with the utility scores. Utility scores using Time Trade-Off (TTO), Visual Analog Scale (VAS), and EuroQol five Dimension (EQ-5D) were obtained from 300 people aged 16 and over by face-to-face interviews. We measured utilities for three hypothetical health states of epilepsy for which scenarios were defined based on the frequency of partial seizure: seizure-free, seizure reduction, and withdrawal. We compared utilities with varying seizure frequency using a repeated-measures ANOVA, and analyzed the association between utilities and socio-demographic characteristics using a generalized estimating equation (GEE). The mean utility scores for withdrawal state, seizure reduction state, and seizure-free state were 0.303, 0.493, and 0.899, respectively, when measured by TTO. VAS yielded the mean utility scores of 0.211, 0.424, and 0.752 for respective health states, and corresponding scores with EQ-5D were 0.261, 0.645, and 0.959. The utility scores for the three health states were statistically different in TTO, VAS, and EQ-5D. The withdrawal state had the lowest utility scores. There were differences in mean utilities for the three health states across the three methods. Utilities by EQ-5D tended to have higher values than those by TTO and VAS. Utilities by VAS had the lowest values. In GEE analysis, the severity of epilepsy and household income were significantly related to utility scores. The withdrawal state of epilepsy had the lowest utility value and the seizure-free state had the highest by all three techniques of utility measurement used. There were significant differences in utilities between one severity level of epilepsy and another. Utility was associated with household income and the severity of disease. Utility scores for distinct epilepsy states obtained in this study could facilitate health economic analyses of epilepsy treatments and thus help decision making in resource allocation. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of epilepsy on autistic symptom severity assessed by the social responsiveness scale in children with autism spectrum disorder.

PubMed

Ko, Chanyoung; Kim, Namwook; Kim, Eunjoo; Song, Dong Ho; Cheon, Keun-Ah

2016-06-27

As the prevalence of autism spectrum disorders in people with epilepsy ranges from 15 to 47 % (Clarke et al. in Epilepsia 46:1970-1977, 2005), it is speculated that there is a special relationship between the two disorders, yet there has been a lack of systematic studies comparing the behavioral phenotype between autistic individuals and autistic individuals with epilepsy. This study aims to investigate how the co-occurrence of epilepsy and Autism Spectrum Disorder (ASD) affects autistic characteristics assessed by the Social Responsiveness Scale (SRS), which has been used as a measure of autism symptoms in previous studies. In this research we referred to all individuals with Autism or Autistic Disorder as individuals with ASD. We reviewed the complete medical records of 182 participants who presented to a single tertiary care referral center from January 1, 2013 to July 28, 2015, and subsequently received complete child and adolescent psychiatric assessments. Of the 182 participants, 22 were diagnosed with Autism Spectrum Disorder and epilepsy. Types of epilepsy observed in these individuals included complex partial seizure, generalized tonic-clonic seizure, or infantile spasm. Using 'Propensity Score Matching' we selected 44 children, diagnosed with only Autism Spectrum Disorder, whose age, gender, and intelligence quotient (IQ) were closely matched with the 22 children diagnosed with Autism Spectrum Disorder and epilepsy. Social functioning of participants was assessed by the social responsiveness scale, which consists of five categories: social awareness, social cognition, social communication, social motivation, and autistic mannerisms. Bivariate analyses were conducted to compare the ASD participants with epilepsy group with the ASD-only group on demographic and clinical characteristics. Chi square and t test p values were calculated when appropriate. There was no significant difference in age (p = 0.172), gender (p > 0.999), IQ (FSIQ, p = 0.139; VIQ, p = 0.114; PIQ, p = 0.295) between the two groups. ASD participants with epilepsy were significantly more impaired than ASD participants on some measures of social functioning such as social awareness (p = 0.03) and social communication (p = 0.027). ASD participants with epilepsy also scored significantly higher on total SRS t-score than ASD participants (p = 0.023). Understanding the relationship between ASD and epilepsy is critical for appropriate management (e.g. social skills training, seizure control) of ASD participants with co-occurring epilepsy. Results of this study suggest that mechanisms involved in producing epilepsy may play a role in producing or augmenting autistic features such as poor social functioning. Prospective study with larger sample sizes is warranted to further explore this association.

Emission computed tomography of /sup 18/F-fluorodeoxyglucose and /sup 13/N-ammonia in stroke and epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhl, D.E.; Phelps, M.E.; Engel, J. Jr.

1980-01-01

The ECAT Positron Tomograph was used to scan normal control subjects, stroke patients at various times during recovery, and patients with partial epilepsy during EEG monitoring. /sup 18/F-fluorodeoxyglucose (/sup 18/FDG) and /sup 13/N-Ammonia (/sup 13/NH/sub 3/) were used as indicators of abnormalities in local cerebral glucose utilization (LCMR/sub glc/) and relative perfusion, respectively. Hypometabolism, due to deactivation or minimal damage, was demonstrated with the /sup 18/FDG scan in deep structures and broad zones of cerebral cortex which appeared normal on x-ray CT (XCT) and /sup 99m/Tc pertechnetate scans. In patients with partial epilepsy, who had unilateral or focal electrical abnormalities,more » interictal /sup 18/FDG scan patterns clearly showed localized regions of decreased (20 to 50%) LCMR/sub glc/, which correlated anatomically with the eventual EEG localization.« less

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks

PubMed Central

Soper, Colin; Wicker, Evan; Kulick, Catherine V.; N’Gouemo, Prosper; Forcelli, Patrick A.

2016-01-01

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. PMID:26721319

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks.

PubMed

Soper, Colin; Wicker, Evan; Kulick, Catherine V; N'Gouemo, Prosper; Forcelli, Patrick A

2016-03-01

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

Inherited epilepsy in dogs.

PubMed

Ekenstedt, Kari J; Oberbauer, Anita M

2013-05-01

Epilepsy is the most common neurologic disease in dogs and many forms are considered to have a genetic basis. In contrast, some seizure disorders are also heritable, but are not technically defined as epilepsy. Investigation of true canine epilepsies has uncovered genetic associations in some cases, however, many remain unexplained. Gene mutations have been described for 2 forms of canine epilepsy: primary epilepsy (PE) and progressive myoclonic epilepsies. To date, 9 genes have been described to underlie progressive myoclonic epilepsies in several dog breeds. Investigations into genetic PE have been less successful, with only 1 causative gene described. Genetic testing as an aid to diagnosis, prognosis, and breeding decisions is available for these 10 forms. Additional studies utilizing genome-wide tools have identified PE loci of interest; however, specific genetic tests are not yet developed. Many studies of dog breeds with PE have failed to identify genes or loci of interest, suggesting that, similar to what is seen in many human genetic epilepsies, inheritance is likely complex, involving several or many genes, and reflective of environmental interactions. An individual dog's response to therapeutic intervention for epilepsy may also be genetically complex. Although the field of inherited epilepsy has faced challenges, particularly with PE, newer technologies contribute to further advances. © 2013 Elsevier Inc. All rights reserved.

Initial experience with SPECT imaging of the brain using I-123 p-iodoamphetamine in focal epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaManna, M.M.; Sussman, N.M.; Harner, R.N.

1989-06-01

Nineteen patients with complex partial seizures refractory to medical treatment were examined with routine electroencephalography (EEG), video EEG monitoring, computed tomography or magnetic resonance imaging, neuropsychological tests and interictal single photon emission computed tomography (SPECT) with I-123 iodoamphetamine (INT). In 18 patients, SPECT identified areas of focal reduction in tracer uptake that correlated with the epileptogenic focus identified on the EEG. In addition, SPECT disclosed other areas of neurologic dysfunction as elicited on neuropsychological tests. Thus, IMP SPECT is a useful tool for localizing epileptogenic foci and their associated dynamic deficits.

"I don't want them to look at me and think of my illness, I just want them to look at me and see me": Child perspectives on the challenges associated with disclosing an epilepsy diagnosis to others.

PubMed

Benson, Ailbhe; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K

2015-12-01

Disclosure of a concealable stigmatized identity, such as epilepsy, to those external to the nuclear family can be complex. Among children living with epilepsy (CWE), diagnosis disclosure has been identified as a quality-of-life issue and a source of psychosocial distress. Despite this, limited empirical evidence exists regarding the disclosure experiences of CWE. This study aimed to identify the contextual factors that act as challenges for CWE when disclosing their epilepsy diagnosis to others external to the nuclear family. This qualitative exploratory study consisted of individual interviews with 29 CWE (aged 6-16 years; mean age=11.17 years; S.D.=2.85). Participants were recruited from a tertiary referral unit in the neurology department of a pediatric hospital and through a national epilepsy association. Interviews were audiotaped and transcribed verbatim. Data were thematically analyzed. The five main challenges to epilepsy diagnosis disclosure for children were: 1) CWE's desire for normalcy, 2) out of sight but in the mind, 3) contending with negative responses to disclosure, 4) the complexity of epilepsy, and 5) self and others' perceptions of epilepsy. These findings provide valuable insight into the factors that present difficulties and impede epilepsy diagnosis disclosure among CWE. Such knowledge is important in informing engagements between health-care professionals (HCPs) and CWE. In particular, HCPs should remain cognisant of the challenges CWE face as they: (i) strive for normalcy and (ii) grapple with comprehending their complex neurological condition. Tackling such disclosure challenges could serve to enhance life quality, improve CWE's openness with others about epilepsy, and consequently work toward reducing epilepsy-related misconceptions and stigma. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluating whole genome sequence data from the Genetic Absence Epilepsy Rat from Strasbourg and its related non-epileptic strain

PubMed Central

Powell, Kim L.; Zhu, Mingfu; Campbell, C. Ryan; Maia, Jessica M.; Ren, Zhong; Jones, Nigel C.; O’Brien, Terence J.; Petrovski, Slavé

2017-01-01

Objective The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbreed Wistar rat strain widely used as a model of genetic generalised epilepsy with absence seizures. As in humans, the genetic architecture that results in genetic generalized epilepsy in GAERS is poorly understood. Here we present the strain-specific variants found among the epileptic GAERS and their related Non-Epileptic Control (NEC) strain. The GAERS and NEC represent a powerful opportunity to identify neurobiological factors that are associated with the genetic generalised epilepsy phenotype. Methods We performed whole genome sequencing on adult epileptic GAERS and adult NEC rats, a strain derived from the same original Wistar colony. We also generated whole genome sequencing on four double-crossed (GAERS with NEC) F2 selected for high-seizing (n = 2) and non-seizing (n = 2) phenotypes. Results Specific to the GAERS genome, we identified 1.12 million single nucleotide variants, 296.5K short insertion-deletions, and 354 putative copy number variants that result in complete or partial loss/duplication of 41 genes. Of the GAERS-specific variants that met high quality criteria, 25 are annotated as stop codon gain/loss, 56 as putative essential splice sites, and 56 indels are predicted to result in a frameshift. Subsequent screening against the two F2 progeny sequenced for having the highest and two F2 progeny for having the lowest seizure burden identified only the selected Cacna1h GAERS-private protein-coding variant as exclusively co-segregating with the two high-seizing F2 rats. Significance This study highlights an approach for using whole genome sequencing to narrow down to a manageable candidate list of genetic variants in a complex genetic epilepsy animal model, and suggests utility of this sequencing design to investigate other spontaneously occurring animal models of human disease. PMID:28708842

Linkage disequilibrium between polymorphisms of ABCB1 and ABCC2 to predict the treatment outcome of Malaysians with complex partial seizures on treatment with carbamazepine mono-therapy at the Kuala Lumpur Hospital.

PubMed

Subenthiran, Soobitha; Abdullah, Noor Rain; Joseph, Joyce Pauline; Muniandy, Prem Kumar; Mok, Boon Teck; Kee, Chee Cheong; Ismail, Zakiah; Mohamed, Zahurin

2013-01-01

Carbamazepine (CBZ) is used as the first line of treatment of Complex Partial Seizures (CPS) in the Epilepsy Clinic, Neurology Department of Kuala Lumpur Hospital (KLH). More than 30% of the patients remain drug resistant to CBZ mono-therapy. CBZ is transported by the P-glycoprotein (P-gp). The P-gp encoded by the ABCB1 and ABCC2 genes are expressed in drug resistant patients with epilepsy. A few studies have shown significant association between CBZ resistant epilepsy and Linkage Disequilibrium (LD) with adjacent polymorphisms of these genes. Our study is aimed at determining the correlation between patients' response to CBZ mono-therapy to Single Nucleotide Polymorphisms G2677T and C3435T of the ABCB1 gene as well as G1249A and -24C>T of the ABCC2 gene. 314 patients with CPS were recruited from the Neurology Department of the KLH based on stringent inclusion and exclusion criteria, of whom 152 were responders and the other 162 were non-responders. DNA was extracted from their blood samples and Taqman technology for allelic discrimination was performed. Results were described as genotype frequencies. The SHEsis analysis platform was used to calculate linkage disequilibrium index and infer haplotype frequencies. Haploview was used to do permutation test to obtain a corrected p-value. Resistance to treatment with CBZ mono-therapy was significantly associated with the 2677TT and the 3435TT genotypes while it was not significantly associated with the G1249A and -24C>T polymorphisms. The GCGC haplotype combination of the 2677G>T, 3435C>T, 1249G>A and -24C>T respectively was found to be extremely significant (p = 1.10e-20) with good drug response to CBZ mono-therapy. Linkage disequilibrium between the 2677G>T, 3435C>T, 1249G>A and -24C>T SNPs may be used as a reliable screening marker to determine the treatment outcome of CBZ mono-therapy with CPS irrespective of race or gender.

Clinical management of elderly patients with epilepsy; the use of lacosamide in a single center setting.

PubMed

Rainesalo, Sirpa; Mäkinen, Jussi; Raitanen, Jani; Peltola, Jukka

2017-10-01

Lacosamide (LCM) is a third-generation antiepileptic drug (AED) for which there is limited experience in the treatment of elderly patients with epilepsy. This study was performed to evaluate the use of LCM in this particular patient group, focusing on its tolerability and effectiveness. This is a retrospective, single-center study, in patients over 60years old treated with LCM between 1/2010 and 5/2015. Altogether, 233 elderly patients receiving LCM were identified; of these, 67 fulfilled the inclusion criteria, i.e., LCM administered for at least 2weeks. Lacosamide was initiated for acute seizure disorders (prolonged complex partial seizures, recurrent seizures, or status epilepticus) in 54 patients (81%) and for chronic epilepsy in 13 patients in an outpatient setting. The mean follow-up period for LCM treatment was 14months. The mean daily dose of LCM at the end of follow-up was 368mg (range: 100-600) for those 57 patients that continued treatment. Ten patients (15%) stopped LCM treatment but none because of lack of efficacy and only three patients (4%) because of side effects. The most frequent side effects were dizziness, fatigue, and tremor. Lacosamide was well tolerated even at relatively high doses and in combination therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Epilepsy Surgery for Individuals with TSC

MedlinePlus

... AC, van der Grond J (2003) Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber ... tuberous sclerosis complex. Epilepsy Behav 20:561-565 Shields WD (2004) Surgical Treatment of Refractory Epilepsy. Curr ...

Perampanel. Just another anticonvulsant for partial epilepsy: no progress.

PubMed

2014-07-01

Nearly a dozen antiepileptic drugs have been shown to prevent attacks in patients with partial epilepsy, whether used alone, or in combination when successive single-agent well-conducted treatments have failed. Perampanel (Fycompa, Eisai) an AMPA glutamate receptor antagonist, has been granted marketing authorisation in the European Union and United States, for use in combination with other antiepileptic drugs in patients aged 12 years or older with partial epilepsy. Perampanel has not been compared with other antiepileptic drugs in clinical trials. Its evaluation is based on three comparative, double-blind, placebo-controlled trials, in which perampanel was added to other antiepileptic drugs considered to be inadequately effective. In these trials, after 19 weeks of treatment, its efficacy was only modest: the response rate was at best only about 20% higher than with placebo. Indirect comparison, albeit inherently unreliable, suggests that perampanel is no better than other antiepileptic drugs. Perampanel has frequent and often dose-dependent adverse effects; they mainly include irritability, aggression, impaired alertness and coordination, and weight gain. Cardiac disorders were observed during a long-term trial of perampanel. This possible adverse effect requires further study. Perampanel led to stunted growth in experimental animals. It is not known whether adolescents are also at risk. Perampanel does not appear to be a potent inducer or inhibitor of the cytochrome P450 enzyme system, but its drug interaction profile requires further evaluation. In animal studies, perampanel exposure resulted in increased perinatal mortality. In practice, there is no evidence that perampanel represents a therapeutic advance for patients with partial epilepsy. In addition to its known adverse effects, there are concerns over possible long-term cardiac toxicity and a deleterious effect on growth. Other acceptable solutions, based on better-known drugs, should be discussed with epileptic patients.

Photogenic partial seizures.

PubMed

Hennessy, M J; Binnie, C D

2000-01-01

To establish the incidence and symptoms of partial seizures in a cohort of patients investigated on account of known sensitivity to intermittent photic stimulation and/or precipitation of seizures by environmental visual stimuli such as television (TV) screens or computer monitors. We report 43 consecutive patients with epilepsy, who had exhibited a significant EEG photoparoxysmal response or who had seizures precipitated by environmental visual stimuli and underwent detailed assessment of their photosensitivity in the EEG laboratory, during which all were questioned concerning their ictal symptoms. All patients were considered on clinical grounds to have an idiopathic epilepsy syndrome. Twenty-eight (65%) patients reported visually precipitated attacks occurring initially with maintained consciousness, in some instances evolving to a period of confusion or to a secondarily generalized seizure. Visual symptoms were most commonly reported and included positive symptoms such as coloured circles or spots, but also blindness and subjective symptoms such as "eyes going funny." Other symptoms described included nonspecific cephalic sensations, deja-vu, auditory hallucinations, nausea, and vomiting. No patient reported any clear spontaneous partial seizures, and there were no grounds for supposing that any had partial epilepsy excepting the ictal phenomenology of some or all of the visually induced attacks. These findings provide clinical support for the physiological studies that indicate that the trigger mechanism for human photosensitivity involves binocularly innervated cells located in the visual cortex. Thus the visual cortex is the seat of the primary epileptogenic process, and the photically triggered discharges and seizures may be regarded as partial with secondary generalization.

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.

Febrile Infection-Related Epilepsy Syndrome (FIRES): An Overview of Treatment and Recent Patents.

PubMed

Hon, Kam Lun E Lun; Leung, Alexander K C; Torres, Alcy R

2018-05-08

New-onset refractory status epilepticus (NORSE) refers to a clinical presentation in a patient without active epilepsy or other existing relevant neurological disorder, with new onset of refractory status epilepticus in the absence of a clear acute or active structural, metabolic, or toxic cause. Febrile infection-related epilepsy syndrome (FIRES) is a subset of NORSE that requires a febrile infection between 24 hours and 2 weeks prior to the onset of refractory status epilepticus, with or without fever at the onset of status epilepticus, and with no restriction to the age of the patient. The literature on FIRES is scarce. This article reviews the pathophysiology, clinical features, and various treatment modalities in the treatment of FIRES. A Medline/Pubmed search was conducted using Clinical Queries with the key terms "febrile infection-related epilepsy syndrome", "FIRES", "new-onset refractory status epilepticus" and "NORSE". The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "FIRES", "NORSE" and "febrile epilepsy syndrome" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. FIRES almost invariably begins with a mild nonspecific febrile illness in an otherwise healthy individual. Twenty four hours to two weeks later, seizures begin and quickly become very frequent and worsen, becoming status epilepticus. Seizures can be simple motor, complex partial or secondary generalized. The exact etiology is no known. It is possible that the syndrome is caused by an inflammatory or autoimmune mechanism. Seizures in FIRES are notoriously very difficult to treat. Treatment modalities include, among others, various antiepileptic drugs, ketogenic diet, intravenous corticosteroids, intravenous immunoglobulin, and burst-suppression coma. Outcome is poor; most children are left with significant cognitive disability and refractory epilepsy. Recent patents for the management of FIRES are discussed. FIRES is a rare epilepsy syndrome of unclear etiology in which children, usually of school age, suddenly develop very frequent seizures after a mild febrile illness. Seizures in FIRES are typically recalcitrant and difficult to treat. The prognosis is poor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.

PubMed

Chang, Xian-Chao; Yuan, Hai; Wang, Yi; Xu, Hui-Qin; Hong, Wen-Ke; Zheng, Rong-Yuan

2017-10-25

This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant partial epilepsy. The searches for the original review were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group Specialized Register (6 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant partial epilepsy. Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects, and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. We included five trials (1799 participants) rated at low risk of bias; all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI 1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom (RR 2.90, 95% CI 1.49 to 5.68). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66, 95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The following adverse effects were significantly associated with ESL: dizziness (RR 2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR 4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was rated as moderate to high. ESL reduces seizure frequency when used as an add-on treatment for people with drug-resistant partial epilepsy. The trials included in this review were of short-term duration and focused on adults. One new trial has been included in this update, but the conclusions are unchanged.

Increasing Utilization Of Pediatric Epilepsy Surgery In The United States Between 1997 and 2009

PubMed Central

Pestana Knight, Elia M.; Schiltz, Nicholas K.; Bakaki, Paul M.; Koroukian, Siran M.; Lhatoo, Samden D.; Kaiboriboon, Kitti

2014-01-01

SUMMARY OBJECTIVE To examine national trends of pediatric epilepsy surgery usage in the United States between 1997 and 2009. METHODS We performed a serial cross-sectional study of pediatric epilepsy surgery using triennial data from the Kids’ Inpatient Database from 1997 to 2009. The rates of epilepsy surgery for lobectomies, partial lobectomies, and hemispherectomies in each study year were calculated based on the number of prevalent epilepsy cases in the corresponding year. The age-race-sex adjusted rates of surgeries were also estimated. Mann-Kendall trend test was used to test for changes in the rates of surgeries over time. Multivariable regression analysis was also performed to estimate the effect of time, age, race, and sex on the annual incidence of epilepsy surgery. RESULTS The rates of pediatric epilepsy surgery significantly increased from 0.85 epilepsy surgeries per 1,000 children with epilepsy in 1997 to 1.44 epilepsy surgeries per 1,000 children with epilepsy in 2009. An increment in the rates of epilepsy surgeries was noted across all age groups, in boys and girls, all races, and all payer types. The rate of increase was lowest in blacks and in children with public insurance. The overall number of surgical cases for each study year was lower than 35% of children who were expected to have surgery, based on the estimates from the Connecticut Study of Epilepsy. SIGNIFICANCE In contrast to adults, pediatric epilepsy surgery numbers have increased significantly in the past decade. However, epilepsy surgery remains an underutilized treatment for children with epilepsy. In addition, black children and those with public insurance continue to face disparities in the receipt of epilepsy surgery. PMID:25630252

[The efficacy of intravenous lacosamide in psychiatric hospital].

PubMed

Vakula, I N; Bojko, E O; Vorona, U A; Storozhuk, J A; Nikiforova, E U; Nikiforova, D I; Glazunova, T I

2016-01-01

To evaluate the efficacy and tolerability of intravenous lacosamide (vimpat) in inpatients with frequent partial-onset seizures and affective and cognitive disorders. Fifteen patients were enrolled including 14 patients diagnosed with «organic personality disorder associated with epilepsy» (cryptogenic or symptomatic epilepsy with frequent partial-onset and/or secondary-generalized seizures (serial seizures in some cases) and 1 patient with a preliminary diagnosis of «organic schizophrenia-like disorder», which was changed for «organic personality disorder associated with epilepsy» after examination. Patients were treated with 2--3 antiepileptic drugs (AEDs), but no one of them received earlier lacosamide. Lacosamide was used intravenously in drops in the dose of 200 or 400 mg daily during 5 days. In 4 patients with marked personality disorders, the frequency of seizures decreased by 75%, no seizures were noted after 2--3 days of treatment in 11 patients. A positive effect of lacosamide on the affective sphere and quality-of-life was observed in 11 (73.4%) patients with epilepsy. Mild and moderate adverse effects were found only in 2 patients. It has been concluded that lacosamide demonstrates the high efficacy in patients with frequent drug-resistant seizures.

The Localizing and Lateralizing Value of Auras in Lesional Partial Epilepsy Patients

PubMed Central

Ye, Byoung Seok; Cho, Yang-Je; Jang, Sang Hyun; Lee, Moon Kyu; Lee, Byung In

2012-01-01

Purpose We investigated the localizing and lateralizing values of auras in patients with lesional partial epilepsy on an outpatient basis. Materials and Methods A total of 276 subjects were retrospectively selected for this study if they had a unilateral single lobar lesion based on magnetic resonance image (MRI) results, and their scalp electroencephalography (EEG) findings were not discordant with the MRI-defined lobar localization and lateralization. According to the lesion locations, subjects were considered as having mesial temporal (MTLE), lateral temporal (LTLE), frontal (FLE), parietal (PLE), or occipital (OLE) lobe epilepsies. Auras were classified into 13 categories. Results A hundred and seventy-six subjects (63.8%) had experienced at least one aura. FLE subjects had the fewest number of auras. Epigastric and psychic auras were frequent among MTLE subjects, while visual auras were common in those with PLE and OLE. Somatosensory auras and whole body sensations were more frequent in the subjects with PLE than those without. Autonomic auras were more common in MTLE subjects than in LTLE subjects. Dysphasic auras were more frequently found in left-sided epilepsies. Five pairs of aura categories showed concurrent tendencies, which were the epigastric and autonomic auras, autonomic and emotional auras, visual and vestibular auras, auditory and vestibular auras, and whole-body sensation and auditory auras. Autonomic and emotional auras had a concurrent tendency in left-sided epilepsies, but not in right-sided epilepsies. Conclusion Our results support the previously known localizing value of auras, and suggest that dysphasic auras and the association of emotional and autonomic auras may have a lateralizing value. PMID:22476989

Subjective sleep disturbance in Chinese adults with epilepsy: Associations with affective symptoms.

PubMed

Shen, Yeru; Zhang, Mengmeng; Wang, Yu; Wang, Lanlan; Xu, Xiangjun; Xiao, Gairong; Chen, Jing; Zhang, Ting; Zhou, Nong

2017-09-01

As well as being a very common neurological disease worldwide, epilepsy significantly impairs patients' emotional, behavioral, and cognitive functioning. Sleep disturbances are the most frequent complaint in patients with epilepsy. The present study assesses the impact of a range of affective symptoms on subjective sleep quality and sleep disturbances in Chinese adults with epilepsy. Adults with epilepsy who visited our epilepsy clinic from July 2015 to March 2016 were enrolled in our study. Both patients and healthy controls completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Mini-mental State Examination (MMSE). Subjective sleep quality and sleep disturbances were examined with regard to self-reported symptoms of depression and anxiety, seizure-related factors, and demographic factors. The PSQI scores and ISI scores of patients were significantly higher (indicating lower quality sleep and more serious insomnia) than those of the control group. Symptoms associated with depression and anxiety were independently related to impaired subjective sleep quality and insomnia. Affective symptoms explained more of the variance in PSQI scores and ISI scores than did seizure-related or demographic variables. In addition, these variables also seemed to be less powerful contributing factors to subjective sleep quality and insomnia than affective symptoms, several seizure-related factors, such as seizure control, partial seizures and duration of epilepsy, which are also significantly associated with subjective sleep quality and insomnia. In addition, use of lamotrigine (LTG) was also associated with insomnia and use of clonazepam (CZP) and phenobarbital (PB) with daytime sleepiness in patients with epilepsy. Chinese adults with epilepsy have poorer self-reported subjective sleep quality and a higher prevalence of insomnia than the control group. Depressive- and anxiety-related symptoms independently exert an adverse effect on the subjective sleep quality and insomnia of patients. In addition, seizure control, partial seizures, and the duration of epilepsy affect the quality of sleep and insomnia in patients, but seem less powerful predictors of sleep quality and insomnia than affective symptoms. Early identification and treatment of affective symptoms is of great importance in improving the sleep quality and insomnia of patients with epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

[Contribution of John Hughlings Jackson to the understanding of epilepsy].

PubMed

Balcells Riba, M

1999-01-01

The figure of J.H. Jackson is one of the most relevant in the history of neurology. His longest period not only during his training but also during his professional plenitude took place in the National Hospital. Jackson was a great clinician, wrote many articles and gave a lot of lectures, but never wrote either a treatise or a monograph about his special field. He did not carry out animal experiments. He introduced in Britain the use of the ophthalmoscope in the neurological exploration and founded the journal Brain. He was specially interested in language disorders, paralysis, vertigo, mental disorders, cerebral tumours and above all epilepsy. He systematized what we today know as complex partial crisis, establishing the link between the function of the temporal lobe and the sensorial auras, automatism's, déjà-vu and jamais vu phenomena. He described the uncinate crisis, the topographic progression of the motor partial crisis and its posterior generalisation, establishing the motor pattern of cerebral cortex. The clinical observations of epileptic phenomena, with the influence of the evolutive ideas from Spencer, were the seeds for the elaboration of the evolutive development of the function of the nervous system. His theory about evolution and dissolution of the neurological functions was the starting point for Freud's clinical investigation. The Jacksonian set of ideas were experimentally proved by the neurophysiological work of Sherrington.

Community-based epidemiological study of epilepsy in the Qena governorate in Upper Egypt, a door-to-door survey.

PubMed

Fawi, Gharib; Khedr, Eman M; El-Fetoh, Noha Abo; Thabit, Mohamed N; Abbass, Mohamed A; Zaki, Ahmad F

2015-07-01

The aim of this study is to estimate the epidemiological features of epilepsy in a representative governorate of Upper Egypt. A door-to-door community-based survey study was performed using a sample of 10 areas among various districts of the Qena governorate in Upper Egypt. Six were classified as rural areas, and the remaining four were classified as urban areas, with a total population of 8027 inhabitants. The population was screened using an epilepsy-screening questionnaire. Positive cases with suspected epilepsy were referred to Qena University Hospital to be further evaluated by a qualified neurologist and for further investigations, such as neuroimaging and electroencephalography. One hundred patients had a confirmed diagnosis of epilepsy, with a lifetime prevalence of 12.46/1000. The active prevalence rate of epilepsy was 2.12/1000, while the incidence rate was 123/100000. Seventy-six percent of the patients had idiopathic epilepsies, while 24% had symptomatic epilepsy. Generalized epilepsies were more common (70.1%) than partial epilepsy (26.3%), meanwhile epilepsies with mixed seizure types were 2.6%. The most common seizure type was generalized tonic clonic seizures (51.8%). The age-specific prevalence rate of epilepsy was much higher in infancy and early childhood (62.5 and 37.04/1000, respectively), which regressed steadily with age. Idiopathic epilepsies were significantly more common in urban areas than in rural areas (P=0.01), while symptomatic epilepsies were more common in rural areas than in urban areas (P<0.005). Upper Egypt is characterized by a relatively high incidence and prevalence of epilepsy and epilepsy-related medical service, and more cultural education should be directed to those areas in Egypt. Copyright © 2015 Elsevier B.V. All rights reserved.

Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency.

PubMed

Almalki, Abdulraheem; Alston, Charlotte L; Parker, Alasdair; Simonic, Ingrid; Mehta, Sarju G; He, Langping; Reza, Mojgan; Oliveira, Jorge M A; Lightowlers, Robert N; McFarland, Robert; Taylor, Robert W; Chrzanowska-Lightowlers, Zofia M A

2014-01-01

Mitochondrial aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in protein synthesis since they charge tRNAs with their cognate amino acids. Mutations in the genes encoding mitochondrial aaRSs have been associated with a wide spectrum of human mitochondrial diseases. Here we report the identification of pathogenic mutations (a partial genomic deletion and a highly conserved p. Asp325Tyr missense variant) in FARS2, the gene encoding mitochondrial phenylalanyl-tRNA synthetase, in a patient with early-onset epilepsy and isolated complex IV deficiency in muscle. The biochemical defect was expressed in myoblasts but not in fibroblasts and associated with decreased steady state levels of COXI and COXII protein and reduced steady state levels of the mt-tRNA(Phe) transcript. Functional analysis of the recombinant mutant p. Asp325Tyr FARS2 protein showed an inability to bind ATP and consequently undetectable aminoacylation activity using either bacterial tRNA or human mt-tRNA(Phe) as substrates. Lentiviral transduction of cells with wildtype FARS2 restored complex IV protein levels, confirming that the p.Asp325Tyr mutation is pathogenic, causing respiratory chain deficiency and neurological deficits on account of defective aminoacylation of mt-tRNA(Phe). © 2013. Published by Elsevier B.V. All rights reserved.

Efficacy and Tolerability of Lacosamide in the Treatment of Children With Refractory Generalized Epilepsy.

PubMed

Miskin, Chandrabhaga; Khurana, Divya S; Valencia, Ignacio; Legido, Agustin; Hasbani, Daphne M; Carvalho, Karen S

2016-06-01

Lacosamide is FDA-approved in patients 17 years or older with partial-onset epilepsy. We evaluated the efficacy and tolerability of lacosamide in children with refractory generalized epilepsy. We retrospectively reviewed records of 21 children with refractory generalized epilepsy treated with lacosamide in our institution from 2009-2013 divided into 2 subgroups- I, Lennox-Gastaut Syndrome, and II, other generalized epilepsies. Efficacy was defined as seizure freedom or ≥50% seizure reduction. Descriptive data analysis including seizure freedom was compared using c(2) analysis. There were eleven females and ten males with a mean age, of 11.9 years. Five patients became seizure free, nine had ≥50% seizure reduction, and seven had no response. Group I: seven had ≥50% improvement, one did not respond. Group II: five became seizure free, two had ≥50% improvement, five had no response. Lacosamide is effective and well tolerated in children with refractory generalized epilepsy particularly patients with Lennox-Gastaut Syndrome. © The Author(s) 2016.

[A surgical case of mesial temporal lobe epilepsy associated with hippocampal sclerosis and traumatic neocortical lesion].

PubMed

Kitazawa, Yu; Jin, Kazutaka; Iwasaki, Masaki; Suzuki, Hiroyoshi; Tanaka, Fumiaki; Nakasato, Nobukazu

2017-11-25

A 26-year-old right-handed woman, with a history of left temporal lobe contusion caused by a fall at the age of 9 months, started to have complex partial seizures with oral automatism at the age of 7 years. The seizures occurred once or twice a month despite combination therapy with several antiepileptic agents. Her history and imaging studies suggested the diagnosis of epilepsy arising from traumatic neocortical temporal lesion. Comprehensive assessment including long-term video EEG monitoring, MRI, FDG-PET, MEG, and neuropsychological evaluation was performed at the age of 26 years. The diagnosis was left mesial temporal lobe epilepsy associated with hippocampal atrophy and traumatic temporal cortical lesion. The patient was readmitted for surgical treatment at the age of 27 years. Intracranial EEG monitoring showed that ictal discharges started in the left hippocampus and spread to the traumatic lesion in the left posterior superior temporal gyrus 10 seconds after the onset. This case could not be classified as dual pathology exactly, because the traumatic left temporal cortical lesion did not show independent epileptogenicity. However, the traumatic lesion was highly likely to be the source of the epileptogenicity, and she had right hemispheric dominance for language and functional deterioration in the whole temporal cortex. Therefore, left amygdalo-hippocampectomy and left temporal lobectomy including the traumatic lesion were performed according to the diagnosis of dual pathology. Subsequently, she remained seizure-free for 3 years. Comprehensive assessment of seizure semiology, neurophysiology, neuroradiology, and neuropsychology is important to determine the optimum therapeutic strategies for drug-resistant epilepsy.

Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

PubMed Central

Wormuth, Carola; Lundt, Andreas; Henseler, Christina; Müller, Ralf; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

2016-01-01

Background: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Cav2.1 P/Q-type and Cav3.2 T-type Ca2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g. in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate. Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca2+ homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Cav2.3 R-type VGCCs in generalized convulsive tonic–clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity. Conclusion: Development of novel Cav2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders. PMID:27843503

Altered activity-rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the β2 nicotinic receptor

PubMed Central

Xu, Jian; Cohen, Bruce N.; Zhu, Yongling; Dziewczapolski, Gustavo; Panda, Satchidananda; Lester, Henry A.; Heinemann, Stephen F.; Contractor, Anis

2010-01-01

High-affinity nicotinic receptors containing beta2 subunits (β2*) are widely expressed in the brain, modulating many neuronal processes and contributing to neuropathologies such as Alzheimer’s disease, Parkinson’s disease and epilepsy. Mutations in both the α4 and β2 subunits are associated with a rare partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Here we introduced one such human missense mutation into the mouse genome to generate a knock-in strain carrying a valine-to-leucine mutation β2V287L.β2V287L mice were viable and born at an expected Mendelian ratio. Surprisingly, mice did not display an overt seizure phenotype; however homozygous mice did display significant alterations in their activity-rest patterns. This was manifest as an increase in activity during the light cycle suggestive of disturbances in the normal sleep patterns of mice; a parallel phenotype to that found in human ADNFLE patients. Consistent with the role of nicotinic receptors in reward pathways, we found that β2V287L mice did not develop a normal proclivity to voluntary wheel running, a model for natural reward. Anxiety-related behaviors were also affected by the V287L mutation. Mutant mice spent more time in the open arms on the elevated plus maze (EPM) suggesting that they had reduced levels of anxiety. Together, these findings emphasize several important roles of β2* nicotinic receptors in complex biological processes including the activity-rest cycle, natural reward, and anxiety. PMID:20603624

[Electroencephalography and epileptology in the 20th century].

PubMed

Karbowski, K

1995-12-05

In 1875, Caton was already able to detect cerebral electric currents during experimental studies in animals. In 1914, Cybulski and Jeleńska-Macieszyna reported on the increase of current-intensity during a focal motor epileptic seizure. In 1929 in Jena, Berger revolutionized the study of epilepsy with his paper on the human electroencephalogram 'Uber das Elektrenkephalogramm des Menschen'. His discovery and further publications as well as later works of numerous researchers, especially F. and E. Gibbs, Lennox, Penfield and Jasper, made it possible to distinguish different forms of 'little' epileptic seizures and to separate them from nonepileptic paroxysmal disorders. New epileptic syndromes could be singled out, as e.g. the symptomatic epilepsy of childhood with variable clinical manifestations of seizures and slow spike-wave complexes in the EEG (Lennox-Gastaut syndrome) or the benign partial epilepsy of childhood with centrotemporal EEG spikes. In these fields, as well as for the epileptic seizures in newborns and babies and for the differentiation between epileptic and nonepileptic twilight states in later stages of life, the EEG remains an indispensable tool in the CT and MRI era. It also contributes largely to the diagnosis of nonepileptic cerebral illness such as herpes simplex encephalitis, subacute sclerosing panencephalitis van Bogaert and Creutzfeldt-Jakob disease. Since the introduction of phenobarbital by Hauptmann in 1912, the palet of effective drugs against epilepsy, such as phenytoin, carbamazepine, valproate and benzodiazepines used for status-epilepticus treatment, became essentially larger. The value of newer substances (vigabatrin, progabide, gabapentin, lamotrigin) can't be estimated actually.(ABSTRACT TRUNCATED AT 250 WORDS)

Chimera states in brain networks: Empirical neural vs. modular fractal connectivity

NASA Astrophysics Data System (ADS)

Chouzouris, Teresa; Omelchenko, Iryna; Zakharova, Anna; Hlinka, Jaroslav; Jiruska, Premysl; Schöll, Eckehard

2018-04-01

Complex spatiotemporal patterns, called chimera states, consist of coexisting coherent and incoherent domains and can be observed in networks of coupled oscillators. The interplay of synchrony and asynchrony in complex brain networks is an important aspect in studies of both the brain function and disease. We analyse the collective dynamics of FitzHugh-Nagumo neurons in complex networks motivated by its potential application to epileptology and epilepsy surgery. We compare two topologies: an empirical structural neural connectivity derived from diffusion-weighted magnetic resonance imaging and a mathematically constructed network with modular fractal connectivity. We analyse the properties of chimeras and partially synchronized states and obtain regions of their stability in the parameter planes. Furthermore, we qualitatively simulate the dynamics of epileptic seizures and study the influence of the removal of nodes on the network synchronizability, which can be useful for applications to epileptic surgery.

Disparities in epilepsy surgery in the United States of America.

PubMed

Sánchez Fernández, Iván; Stephen, Christopher; Loddenkemper, Tobias

2017-08-01

The aim is to describe the epidemiology of epilepsy surgery in children and adults in the United States. We performed a descriptive study of the National Inpatient Sample (NIS) for the year 2012 and the Kids' Inpatient Database (KID) for the period 2010-2012, the largest all-payer databases on inpatient data in the USA. These databases estimate 97% of all inpatient hospital discharges in the USA. In the KID, 12,899 (0.2%) of admission records had brain surgery and 600 of the 4900 (12.2%) admissions with focal refractory epilepsy underwent epilepsy surgery. Epilepsy surgery occurred in 60% of Whites, 7% of Blacks, 15% of Hispanics, and 10% of other races. In the NIS, 99,650 (0.3%) of admission records had brain surgery and 1170 of the 9775 (12%) admissions with focal refractory epilepsy underwent epilepsy surgery. Epilepsy surgery occurred in 69% of Whites, 7% of Blacks, 9% of Hispanics, and 8% of other races. In both the KID and the NIS, lower socioeconomic status was mildly underrepresented in epilepsy surgery. In both pediatric and adult admissions, there was an overrepresentation of Whites and underrepresentation of Blacks, which persisted after stratifying by socioeconomic status. Females were underrepresented in epilepsy surgery, but gender disparities were partially explained by differences in socioeconomic status. Epilepsy surgery is not equally distributed across races in the USA and these differences are not fully attributable to differences in socioeconomic status. Racial disparities in epilepsy surgery similarly affect children and adults.

Pre- and postoperative memory of dichotically presented words in patients with complex partial seizures.

PubMed

Christianson, S A; Nilsson, L G; Silfvenius, H

1989-01-01

Dichotic listening tests were used to determine cerebral hemisphere memory functions in patients with complex partial seizures before, 10 days after, and 1-3 yr after right (RTE) or left (LTE) temporal-lobe excisions. Control subjects were also tested on two occasions. The tests consisted of presenting a series of 12-word lists and 7-word lists alternately to the two ears while backward speech was presented to the other ear. Measures of immediate free recall, final free recall, final cued recall, and serial recall were employed. The results revealed: (a) that both groups of patients were inferior the control group in tests tapping long-term memory functions rather than short-term memory functions, (b) a right-ear advantage for RTE patients at postoperative testing, (c) that the LTE group was more affected by surgery than the RTE group, and (d) a general improvement in recall performance from early to late postoperative testing. Taken together, these results indicate that the present dichotic test can be used as a non-invasive hemisphere memory test to complement invasive techniques for diagnosis of patients considered for epilepsy surgery.

The Pivotal Role of the Parieto-Occipital Lobe in Card Game-Induced Reflex Epilepsy: A Voxel-Based Morphometry Study.

PubMed

Park, Kang Min; Kim, Sung Eun; Lee, Byung In

2016-01-01

The pathogenesis of card game-induced reflex epilepsy has not been determined so far. The aim of this study was to evaluate structural abnormalities using voxel-based morphometry (VBM) analysis, which may give some clue about the pathogenesis in card game-induced reflex epilepsy. The 3 subjects were diagnosed with card game-induced reflex epilepsy. Evaluation involved a structured interview to obtain clinical information and brain MRI. In VBM analysis, Statistical Parametric Mapping 8 running on the MATLAB platform was employed to analyze the structural differences between patients with card game-induced reflex epilepsy and age- and sex-matched control subjects. The results of VBM analysis revealed that patients with card game-induced reflex epilepsy had significantly increased gray matter volume in the right occipital and parietal lobe. However, there were no structures with decreased gray matter volume in patients with card game-induced reflex epilepsy compared with control subjects. In addition, we found that the patients with card game-induced reflex epilepsy had onset of seizures in adulthood rather than in adolescence, and all of the patients were men. The parieto-occipital lobes might be partially involved in the neuronal network responsible for card game-induced reflex epilepsy. © 2016 S. Karger AG, Basel.

Computer modeling of Epilepsy

PubMed Central

Lytton, William W.

2009-01-01

Preface Epilepsy is a complex set of disorders that can involve many areas of cortex as well as underlying deep brain systems. The myriad manifestations of seizures, as varied as déjà vu and olfactory hallucination, can thereby give researchers insights into regional functions and relations. Epilepsy is also complex genetically and pathophysiologically, involving microscopic (ion channels, synaptic proteins), macroscopic (brain trauma and rewiring) and intermediate changes in a complex interplay of causality. It has long been recognized that computer modeling will be required to disentangle causality, to better understand seizure spread and to understand and eventually predict treatment efficacy. Over the past few years, substantial progress has been made modeling epilepsy at levels ranging from the molecular to the socioeconomic. We review these efforts and connect them to the medical goals of understanding and treating this disorder. PMID:18594562

Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements.

PubMed

Nixon, Annabel; Kerr, Cicely; Breheny, Katie; Wild, Diane

2013-03-11

Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full, partial or no evidence, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and interpretation of change were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through additional research prior to any FDA regulatory submission, although the NDDI-E was designed as a screening tool and is therefore unlikely to be suitable as an instrument for capturing change in a clinical trial and the SHE lacks the conceptual focus on signs and symptoms favoured by the FDA.

Sudden cardiac arrest in people with epilepsy in the community

PubMed Central

Lamberts, Robert J.; Blom, Marieke T.; Wassenaar, Merel; Bardai, Abdennasser; Leijten, Frans S.; de Haan, Gerrit-Jan; Sander, Josemir W.; Thijs, Roland D.

2015-01-01

Objective: To ascertain whether characteristics of ventricular tachycardia/fibrillation (VT/VF) differed between people with epilepsy and those without and which individuals with epilepsy were at highest risk. Methods: We ascertained 18 people with active epilepsy identified in a community-based registry of sudden cardiac arrest (SCA) with ECG-confirmed VT/VF (cases). We compared them with 470 individuals with VT/VF without epilepsy (VT/VF controls) and 54 individuals with epilepsy without VT/VF (epilepsy controls). Data on comorbidity, epilepsy severity, and medication use were collected and entered into (conditional) logistic regression models to identify determinants of VT/VF in epilepsy. Results: In most cases, there was an obvious (10/18) or presumed cardiovascular cause (5/18) in view of preexisting heart disease. In 2 of the 3 remaining events, near–sudden unexpected death in epilepsy (SUDEP) was established after successful resuscitation. Cases had a higher prevalence of congenital/inherited heart disease (17% vs 1%, p = 0.002), and experienced VT/VF at younger age (57 vs 64 years, p = 0.023) than VT/VF controls. VT/VF in cases occurred more frequently at/near home (89% vs 58%, p = 0.009), and was less frequently witnessed (72% vs 89%, p = 0.048) than in VT/VF controls. Cases more frequently had clinically relevant heart disease (50% vs 15%, p = 0.005) and intellectual disability (28% vs 1%, p < 0.001) than epilepsy controls. Conclusion: Cardiovascular disease rather than epilepsy characteristics is the main determinant of VT/VF in people with epilepsy in the community. SCA and SUDEP are partially overlapping disease entities. PMID:26092917

Multiscale Entropy of Electroencephalogram as a Potential Predictor for the Prognosis of Neonatal Seizures.

PubMed

Lu, Wen-Yu; Chen, Jyun-Yu; Chang, Chi-Feng; Weng, Wen-Chin; Lee, Wang-Tso; Shieh, Jiann-Shing

2015-01-01

Increasing animal studies supported the harmful effects of prolonged or frequent neonatal seizures in developing brain, including increased risk of later epilepsy. Various nonlinear analytic measures had been applied to investigate the change of brain complexity with age. This study focuses on clarifying the relationship between later epilepsy and the changes of electroencephalogram (EEG) complexity in neonatal seizures. EEG signals from 19 channels of the whole brain from 32 neonates below 2 months old were acquired. The neonates were classified into 3 groups: 9 were normal controls, 9 were neonatal seizures without later epilepsy, and 14 were neonatal seizures with later epilepsy. Sample entropy (SamEn), multiscale entropy (MSE) and complexity index (CI) were analyzed. Although there was no significant change in SamEn, the CI values showed significantly decreased over Channels C3, C4, and Cz in patients with neonatal seizures and later epilepsy compared with control group. More multifocal epileptiform discharges in EEG, more abnormal neuroimaging findings, and higher incidence of future developmental delay were noted in the group with later epilepsy. Decreased MSE and CI values in patients with neonatal seizures and later epilepsy may reflect the mixed effects of acute insults, underlying brain immaturity, and prolonged seizures-related injuries. The analysis of MSE and CI can therefore provide a quantifiable and accurate way to decrypt the mystery of neonatal seizures, and could be a promising predictor.

Neuroendocrine considerations in the treatment of men and women with epilepsy

PubMed Central

Harden, Cynthia L; Pennell, Page B

2016-01-01

Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy. PMID:23237902

Interleukin-1β causes fluoxetine resistance in an animal model of epilepsy-associated depression.

PubMed

Pineda, Eduardo A; Hensler, Julie G; Sankar, Raman; Shin, Don; Burke, Teresa F; Mazarati, Andréy M

2012-04-01

Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitary-adrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamo-pituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.

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.

Computer modelling of epilepsy.

PubMed

Lytton, William W

2008-08-01

Epilepsy is a complex set of disorders that can involve many areas of the cortex, as well as underlying deep-brain systems. The myriad manifestations of seizures, which can be as varied as déjà vu and olfactory hallucination, can therefore give researchers insights into regional functions and relations. Epilepsy is also complex genetically and pathophysiologically: it involves microscopic (on the scale of ion channels and synaptic proteins), macroscopic (on the scale of brain trauma and rewiring) and intermediate changes in a complex interplay of causality. It has long been recognized that computer modelling will be required to disentangle causality, to better understand seizure spread and to understand and eventually predict treatment efficacy. Over the past few years, substantial progress has been made in modelling epilepsy at levels ranging from the molecular to the socioeconomic. We review these efforts and connect them to the medical goals of understanding and treating the disorder.

Long-term outcomes of epilepsy surgery in school-aged children with partial epilepsy.

PubMed

Liang, Shuli; Wang, Shuai; Zhang, Junchen; Ding, Chengyun; Zhang, Zhiwen; Fu, Xiangping; Hu, Xiaohong; Meng, Xiaoluo; Jiang, Hong; Zhang, Shaohui

2012-10-01

The pediatric epileptic spectrum and seizure control in surgical patients have been defined in developed countries. However, corresponding data on school-aged children from developing countries are insufficient. We summarized epileptic surgical data from four centers in China, to compare surgical outcomes of school-aged children with intractable partial epilepsy from China and those from developed countries, and introduce surgical candidate criteria. Data from 206 children (aged 6-14 years) undergoing surgical resection for epilepsy between September 2001 and January 2007 were selected. Postoperative freedom from seizures was achieved in 173 cases (84.0%) at 1 year, 149 (72.3%) at 3 years, and 139 (67.5%) at 5 years. Patients with focal magnetic resonance imaging abnormalities and a short history of seizure were most likely to become seizure-free postoperatively. Those with preoperative low intelligence quotients who became seizure-free postoperatively achieved improvements in full memory quotients, intelligence quotients, and overall quality of life at 2 years. Significant differences were evident in mean changes of full intelligence quotient, full memory quotient, and overall quality of life between patients with preoperative low intelligence quotients who received corpus callosotomies and those with a normal preoperative intelligence quotient, and between seizure-free children and those with continual seizures. Copyright © 2012 Elsevier Inc. All rights reserved.

A comparison of the efficacy of carbamazepine and the novel anti-epileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy

PubMed Central

Doheny, H C; Whittington, M A; Jefferys, J G R; Patsalos, P N

2002-01-01

The tetanus toxin seizure model, which is associated with spontaneous and intermittent generalized and non-generalized seizures, is considered to reflect human complex partial epilepsy. The purpose of the present study was to investigate and compare the anticonvulsant effects of carbamazepine with that of levetiracetam, a new anti-epileptic drug in this model. One μl of tetanus toxin solution (containing 12 mLD50 μl−1 of tetanus toxin) was placed stereotactically into the rat left hippocampus resulting in generalized and non-generalized seizures. Carbamazepine (4 mg kg−1 h−1) and levetiracetam (8 and 16 mg kg−1 h−1) were administered during a 7 day period via an osmotic minipump which was placed in the peritoneal cavity. Carbamazepine (4 mg kg−1 h−1) exhibited no significant anticonvulsant effect, compared to control, when the entire 7 day study period was evaluated but the reduction in generalized seizures was greater (35.5%) than that for non-generalized seizures (12.6%). However, during the first 2 days of carbamazepine administration a significant reduction in both generalized seizure frequency (90%) and duration (25%) was observed. Non-generalized seizures were unaffected. This time-dependent anticonvulsant effect exactly paralleled the central (CSF) and peripheral (serum) kinetics of carbamazepine in that steady-state concentrations declined over time, with the highest concentrations achieved during the first 2 days. Also there was a significant 27.3% reduction in duration of generalized seizures during the 7 day study period (P=0.0001). Levetiracetam administration (8 and 16 mg kg−1 h−1) was associated with a dose-dependent reduction in the frequency of both generalized (39 v 57%) and non-generalized (36 v 41%) seizures. However, seizure suppression was more substantial for generalized seizures. Also a significant dose-dependent reduction in overall generalized seizure duration was observed. These data provide experimental evidence for the clinical efficacy of levetiracetam for the management of patients with complex partial seizures. Furthermore, levetiracetam probably does not act by preventing ictogenesis per se but acts to reduce seizure severity and seizure generalization. PMID:11906955

Dictator Perpetuus: Julius Caesar--did he have seizures? If so, what was the etiology?

PubMed

Hughes, John R

2004-10-01

The "Dictator Perpetuus" of the Roman Empire, the great Julius Caesar, was not the one for whom the well-known cesarean operation was named; instead, this term is derived from a Latin word meaning "to cut." Caesar likely had epilepsy on the basis of four attacks that were probably complex partial seizures: (1) while listening to an oration by Cicero, (2) in the Senate while being offered the Emperor's Crown, and in military campaigns, (3) near Thapsus (North Africa) and (4) Corduba (Spain). Also, it is possible that he had absence attacks as a child and as a teenager. His son, Caesarion, by Queen Cleopatra, likely had seizures as a child, but the evidence is only suggestive. His great-great-great grandnephews Caligula and Britannicus also had seizures. The etiology of these seizures in this Julio-Claudian family was most likely through inheritance, with the possibility of sudden unexpected death in epilepsy (SUDEP) in his great grandfather and also his father. Our best evidence comes from the ancient sources of Suetonius, Plutarch, Pliny, and Appianus.

Novel, broad-spectrum anticonvulsants containing a sulfamide group: pharmacological properties of (S)-N-[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112).

PubMed

McComsey, David F; Smith-Swintosky, Virginia L; Parker, Michael H; Brenneman, Douglas E; Malatynska, Ewa; White, H Steve; Klein, Brian D; Wilcox, Karen S; Milewski, Michael E; Herb, Mark; Finley, Michael F A; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B; Maryanoff, Bruce E

2013-11-27

Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels and was effective as a K(+) channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.

Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Pharmacological Properties of (S)-N-[(6-Chloro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]sulfamide (JNJ-26489112)

PubMed Central

McComsey, David F.; Smith-Swintosky, Virginia L.; Parker, Michael H.; Brenneman, Douglas E.; Malatynska, Ewa; White, H. Steve; Klein, Brian D.; Wilcox, Karen S.; Milewski, Michael E.; Herb, Mark; Finley, Michael F. A.; Liu, Yi; Lubin, Mary Lou; Qin, Ning; Reitz, Allen B.; Maryanoff, Bruce E.

2014-01-01

Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such “neurostabilizers” have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4–9, 10a–i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically-induced, and chemically-induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels, and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies. PMID:24205976

CE: Epilepsy Update, Part 1: Refining Our Understanding of a Complex Disease.

PubMed

Smith, Gigi; Wagner, Janelle L; Edwards, Jonathan C

2015-05-01

Epilepsy is a serious, common neurologic disease that affects people of all ages. As underscored in the 2012 Institute of Medicine report Epilepsy Across the Spectrum: Promoting Health and Understanding, the millions of people living with epilepsy in the United States face the challenges of seeking out high-quality, coordinated health care and community services; overcoming epilepsy misinformation and stigma; and finding understanding and support in their communities. This article, the first in a two-part series, discusses new research that has increased our understanding of epilepsy's etiology and pathophysiology, new definitions that are changing the ways we evaluate and treat this disease, conditions that frequently present with epilepsy, and psychosocial challenges faced by people with epilepsy. Part 2, which will appear in next month's issue, reviews comprehensive nursing care and evidence-based treatment for epilepsy and presents resources for people with epilepsy and their families.

Outcomes from a nurse-led clinic for adolescents with epilepsy.

PubMed

Stephen, Linda J; Maxwell, Jan; Brodie, Martin J

2003-12-01

Epilepsy is the commonest serious neurological condition to affect adolescents. We established a nurse-led clinic for young people with suspected or diagnosed epilepsy. Outcomes in all patients referred during the first 4 years after its inception are reported. A total of 301 adolescents were seen at the clinic during 1996-1999. Epilepsy was excluded in 135 (45%), including 5 receiving antiepileptic drug (AED) therapy. A single seizure occurred in 22 (7%) others. Seventy-six patients (25%) had treated epilepsy and 68 (23%) were newly diagnosed. More than 1 year's seizure freedom was achieved by 53% of patients, 76% with one AED, 16% with two and 3% with three. Four (5%) patients remained seizure free off medication. Sixteen (11%) were lost to follow-up. Outcome was better (P<0.05) for newly diagnosed (59% seizure free) than for treated (47% seizure free) epilepsy and for idiopathic generalised (60% seizure free) than for partial (46% seizure free) seizures (P<0.02). Magnetic resonance imaging of brain was obtained in 63 (85%) patients with localisation-related epilepsy. Findings were abnormal in 43%, including nine with cortical dysplasia, eight with mesial temporal sclerosis and two with gliomas. Epilepsy can be difficult to diagnose in adolescents. Outcomes were surprisingly poor suggesting the need for improved services for this patient population.

The Role of Brain Inflammation in Epileptogenesis in TSC

DTIC Science & Technology

2014-07-01

human temporal lobe epilepsy . Neurobiol Dis 2008;29:142-160. 5. Ravizza T, Noe F, Zardoni D, Vaghi V, Sifringer M, Vezzani A. Interleukin...of epilepsy , as well as in human tissue obtained from epilepsy patients, such as with mesial temporal sclerosis. Different types of inflammatory...14. ABSTRACT Epilepsy is a common, disabling problem in patients with tuberous sclerosis complex (TSC) and is usually intractable to available

MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures.

PubMed

Escalante-Santiago, David; Feria-Romero, Iris Angélica; Ribas-Aparicio, Rosa María; Rayo-Mares, Dario; Fagiolino, Pietro; Vázquez, Marta; Escamilla-Núñez, Consuelo; Grijalva-Otero, Israel; López-García, Miguel Angel; Orozco-Suárez, Sandra

2014-01-01

Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR.

MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures

PubMed Central

Escalante-Santiago, David; Feria-Romero, Iris Angélica; Ribas-Aparicio, Rosa María; Rayo-Mares, Dario; Fagiolino, Pietro; Vázquez, Marta; Escamilla-Núñez, Consuelo; Grijalva-Otero, Israel; López-García, Miguel Angel; Orozco-Suárez, Sandra

2014-01-01

Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR. PMID:25346718

Dravet Syndrome History

ERIC Educational Resources Information Center

Dravet, Charlotte

2011-01-01

Severe myoclonic epilepsy of infancy (SMEI) is a complex form of epilepsy that was first described in France in 1978. Because the myoclonic component of this epilepsy is not always present and because some variability has been observed in the symptomatology, the name was changed to Dravet syndrome in 1989. The genetic aetiology of this epilepsy…

How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?

PubMed

Yuen, Eunice S M; Sims, John R

2014-06-01

Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature. A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically. The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51). Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

PubMed

Wolf, Peter

2017-06-01

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

Patients' and neurologists' perception of epilepsy and psychogenic nonepileptic seizures.

PubMed

Whitehead, Kimberley; Kandler, Rosalind; Reuber, Markus

2013-04-01

Although differences in illness perceptions between neurologists and patients with epilepsy or psychogenic nonepileptic seizures (PNES) are likely to be clinically relevant, this is the first study to attempt a direct comparison. In addition, this study compares the illness perceptions of patients with epilepsy with those of patients with PNES. Thirty-four patients with epilepsy, 40 patients with PNES, and 45 neurologists were recruited. All patient participants completed versions of the illness perception questionnaire revised (IPQ-R) adapted for epileptic or nonepileptic seizure disorders, single-item symptom attribution question (SAQ), Hospital Anxiety and Depression Scale (HADS), Quality of Life in Epilepsy-31 (QOLIE-31), and Liverpool Seizure Severity Scale (LSSS). Participating neurologists completed two versions of the IPQ-R and two SAQs for epileptic and nonepileptic seizure disorders. Differences in illness perceptions between patients with epilepsy and patients with PNES were minor compared to those between patients with either seizure disorder and neurologists. Neurologists considered both seizure disorders more treatable and more amenable to personal control than did the patients themselves. Neurologists had much more polarized views of the etiology of both conditions; whereas patients mostly considered the causes of their seizure disorders as partially "physical" and partially "psychological," neurologists perceived epilepsy as an essentially "physical" and PNES as a clearly "psychological" problem. There are considerable differences between the illness perceptions of patients with seizure disorders and their doctors, which could represent barriers to successful clinical management. In particular, a discrepancy between neurologists' and patients' beliefs about the personal control that patients may be able to exert over PNES could contribute to the confusion or anger some patients report after the diagnosis has been explained to them. Furthermore, patients' endorsement of "physical" causes for PNES may reflect an unrealistic faith in the effectiveness of "physical" treatments and could be a cause of tension in patients' relationship with their doctor, for instance when the neurologist attempts to withdraw antiepileptic drug treatment or refers patients for psychological interventions. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

VGKC complex antibodies in epilepsy: diagnostic yield and therapeutic implications.

PubMed

Lilleker, James B; Jones, Matthew S; Mohanraj, Rajiv

2013-11-01

In a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known. We reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment. We identified 6 (4.2%) patients who had titres of >400 pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis. Patients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.

PubMed

Morrell, Martha J

2011-09-27

This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy. A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation. Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function. Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

Epilepsy and art: Windows into complexity and comorbidities.

PubMed

Schachter, Steven C

2016-04-01

The views of artists with epilepsy as expressed through their art provide unique opportunities to gain understanding of the experiences of living with epilepsy and related comorbidities. This paper provides a glimpse into art collected from an international group of artists with epilepsy, focusing on ictal and postictal experiences, psychiatric comorbidities, and social aspects of epilepsy. The art serves to enhance understanding among clinicians and neuroscientists of what it means to have epilepsy as well as to reduce misunderstanding and stigma among the public. It may also inspire neuroscientists to further explore the underlying neurological basis to the rich tapestries of ictal, postictal, and interictal experiences of persons with epilepsy. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". Copyright © 2015 Elsevier Inc. All rights reserved.

Joan of Arc: Sanctity, witchcraft or epilepsy?

PubMed

Nicastro, Nicolas; Picard, Fabienne

2016-04-01

The objective of this article is to describe whether Joan of Arc had epilepsy and how that may have influenced her sense of mission and ability to encourage thousands of people to help her to chase the English out of France. Documentation of her Trial of Condemnation in 1431 provides a description of her episodes of experienced voices and visions. From the age of thirteen, Joan of Arc experienced frequent episodes of auditory hallucinations associated with elementary or complex visual hallucinations (e.g., a great light or human faces). These had sudden onset, lasting seconds or minutes at most, and occurred when awake or during sleep, arousing her. Some could be triggered by an auditory stimulus. She had no disorganized thought between the episodes. The semiology of the episodes is very suggestive of epileptic seizures, which have been considered as ecstatic by some authors or as partial epilepsy with auditory features by others, which seems more concordant with the ictal symptoms. The auditory and visual hallucinations could have had a religious content because during her childhood and adolescence, she was brought up in a religious environment, insomuch as this content first undefined only appeared after a few seizures. We can suppose that such hallucinations, without the knowledge of their medical origin, gave her a sense of divine mission, hence, a real strength to try to accomplish the orders she heard during the episodes. Her role during the Hundred Years' War and her narration of her strange episodes led her to be burned for heresy at the age of nineteen, yet rehabilitated 25 years later and to be canonized for her achievements in 1920. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". Copyright © 2016 Elsevier Inc. All rights reserved.

The persistence of erroneous familiarity in an epileptic male: challenging perceptual theories of déjà vu activation.

PubMed

O'Connor, Akira R; Moulin, Christopher J A

2008-11-01

We report the case of a 39-year-old, temporal lobe epileptic male, MH. Prior to complex partial seizure, experienced up to three times a day, MH often experiences an aura experienced as a persistent sensation of déjà vu. Data-driven theories of déjà vu formation suggest that partial familiarity for the perceived stimulus is responsible for the sensation. Consequently, diverting attention away from this stimulus should cause the sensation to dissipate. MH, whose sensations of déjà vu persist long enough for him to shift his perceptual focus a number of times during the experience, spontaneously reports that these shifts make no difference to the sensation experienced. This novel observation challenges data-driven theories of déjà vu formation which have been used to explain the occurrence of déjà vu in those with temporal lobe epilepsy and the general population. Clearly, in epilepsy, erratic neuronal firing is the likely contributor, and in this paper we postulate that such brain firing causes higher-order erroneous 'cognitive feelings'. We tentatively extend this account to the general population. Rather than being a reaction to familiar elements in perceptual stimuli, déjà vu is likely to be the result of a cognitive feeling borne of the erroneous activation of neural familiarity circuits such as the parahippocampal gyrus, persisting as long as this activation persists.

Targeted Upregulation of FMRP Expression as an Approach to the Treatment of Fragile X Syndrome

DTIC Science & Technology

2016-10-01

Fragile X syndrome (FXS), the most common heritable form of intellectual disability and most common single-gene form of autism , is caused by partial...15. SUBJECT TERMS Fragile X, autism , FMR1, FXTAS, CGG repeat, epilepsy, seizures, FMRP, PTSD, premutation, iPSC, progenitor, calcium regulation...the most common heritable form of intellectual disability, the most common single-gene form of autism , and a relatively common cause of epilepsy

Movement of Individuals with Complex Epilepsy from an Institution into the Community: Seizure Control and Functional Outcomes.

ERIC Educational Resources Information Center

Litzinger, M. J.; And Others

1993-01-01

This examination of the successful community placement of 15 medically fragile individuals with profound mental retardation and complex epilepsy found that simplification of anticonvulsants, early intervention for seizures, and improved staff education resulted in fewer seizures, decreases in emergency room visits for status seizures and…

Myoclonic Jerks and Schizophreniform Syndrome: Case Report and Literature Review.

PubMed

Endres, Dominique; Altenmüller, Dirk-M; Feige, Bernd; Maier, Simon J; Nickel, Kathrin; Hellwig, Sabine; Rausch, Jördis; Ziegler, Christiane; Domschke, Katharina; Doerr, John P; Egger, Karl; Tebartz van Elst, Ludger

2018-01-01

Background: Schizophreniform syndromes can be divided into primary idiopathic forms as well as different secondary organic subgroups (e.g., paraepileptic, epileptic, immunological, or degenerative). Secondary epileptic explanatory approaches have often been discussed in the past, due to the high rates of electroencephalography (EEG) alterations in patients with schizophrenia. In particular, temporal lobe epilepsy is known to be associated with schizophreniform symptoms in well-described constellations. In the literature, juvenile myoclonic epilepsy has been linked to emotionally unstable personality traits, depression, anxiety, and executive dysfunction; however, the association with schizophrenia is largely unclear. Case presentation: We present the case of a 28-year-old male student suffering from mild myoclonic jerks, mainly of the upper limbs, as well as a predominant paranoid-hallucinatory syndrome with attention deficits, problems with working memory, depressive-flat mood, reduced energy, fast stimulus satiation, delusional and audible thoughts, tactile hallucinations, thought inspirations, and severe sleep disturbances. Cerebral magnetic resonance imaging and cerebrospinal fluid analyses revealed no relevant abnormalities. The routine EEG and the first EEG after sleep deprivation (under treatment with oxazepam) also returned normal findings. Video telemetry over one night, which included a partial sleep-deprivation EEG, displayed short generalized spike-wave complexes and polyspikes, associated with myoclonic jerks, after waking in the morning. Video-EEG monitoring over 5 days showed over 100 myoclonic jerks of the upper limbs, frequently with generalized spike-wave complexes with left or right accentuation. Therefore, we diagnosed juvenile myoclonic epilepsy. Discussion: This case report illustrates the importance of extended EEG diagnostics in patients with schizophreniform syndromes and myoclonic jerks. The schizophreniform symptoms in the framework of epileptiform EEG activity can be interpreted as a (para)epileptic mechanism due to local area network inhibition (LANI). Following the LANI hypothesis, paranoid hallucinatory symptoms are not due to primary excitatory activity (as myoclonic jerks are) but rather to the secondary process of hyperinhibition triggered by epileptic activity. Identifying subgroups of schizophreniform patients with comorbid epilepsy is important because of the potential benefits of optimized pharmacological treatment.

[Sexual disorders in epilepsy. Results of a multidisciplinary evaluation].

PubMed

Silva, H C; Carvalho, M J; Jorge, C L; Cunha Neto, M B; Goes, P M; Yacubian, E M

1999-09-01

Eleven epileptic men who complained of epilepsy and sexual dysfunction were submitted to a multidisciplinary evaluation. Mean age was 27 years (20-34), mean epilepsy duration was 19 years (0.5-32) and the mean seizure frequency was two by week (0-7). Ten patients had partial seizures and one other had myoclonic epilepsy. Ten patients were treated with antiepileptic drugs (phenytoin--1, carbamazepine--8, clonazepam--3, clobazam--2, valproic acid--3, vigabatrin--1). As defined in the DSM III-R, the complaints were: erectile disorder (9), hypoactive sexual desire disorder (4), frotteurism (4), inhibited orgasm (3), premature ejaculation (3), fetishism (2), voyeurism (2), exhibitionism (2), pedophilia (1) and sexual aversion disorder (1). Two patients showed hypogonadotropic hypogonadism on endocrinologic screening. Urological evaluation disclosed organic erectile dysfunction in other two. One patient had a diagnosis of psychogenic sexual disorder. In six patients a conclusive etiologic diagnosis was not reached. This report shows the multifactorial nature of sexual disorder in epilepsy and underlies the need of a multidisciplinar evaluation.

Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms.

PubMed

Cunliffe, Vincent T; Baines, Richard A; Giachello, Carlo N G; Lin, Wei-Hsiang; Morgan, Alan; Reuber, Markus; Russell, Claire; Walker, Matthew C; Williams, Robin S B

2015-01-01

This narrative review is intended to introduce clinicians treating epilepsy and researchers familiar with mammalian models of epilepsy to experimentally tractable, non-mammalian research models used in epilepsy research, ranging from unicellular eukaryotes to more complex multicellular organisms. The review focuses on four model organisms: the social amoeba Dictyostelium discoideum, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. We consider recent discoveries made with each model organism and discuss the importance of these advances for the understanding and treatment of epilepsy in humans. The relative ease with which mutations in genes of interest can be produced and studied quickly and cheaply in these organisms, together with their anatomical and physiological simplicity in comparison to mammalian species, are major advantages when researchers are trying to unravel complex disease mechanisms. The short generation times of most of these model organisms also mean that they lend themselves particularly conveniently to the investigation of drug effects or epileptogenic processes across the lifecourse. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Eslicarbazepine acetate for the treatment of partial epilepsy.

PubMed

Zelano, Johan; Ben-Menachem, Elinor

2016-06-01

Eslicarbazepine acetate (ESL) is a third generation AED structurally related to carbamazepine and oxcarbazepine, but without several of the drawbacks associated with these compounds. ESL is completely metabolized to its eslicarbazpine, which selectively binds inactivated voltage-gated sodium channels and thus selectively reduces the activity of rapidly firing (epileptic) neurons. In addition, ESL has pharmacokinetic properties allowing once daily dosing. This review summarizes data from the initial phase I to III studies, which demonstrated efficacy of ESL as add-on treatment in partial onset epilepsy, and more recent studies that demonstrate efficacy of ESL as monotherapy. Real-life observational studies are also reviewed, and seem to confirm the notion of ESL as a well-tolerated AED. As a new AED, ESL needs to be subject to close monitoring regarding long-term adverse events. Future independent studies will most likely clarify the role of ESL in the management of partial onset seizures. The role of ESL in management of partial onset seizures is discussed, as is the need for close monitoring and evaluation for broad-spectrum pharmacodynamics properties. The characteristics of the molecule and efficacy and safety profiles seem, however, very promising.

Epilepsy and optogenetics: can seizures be controlled by light?

PubMed

Tønnesen, Jan; Kokaia, Merab

2017-07-15

Over the past decade, 'optogenetics' has been consolidated as a game-changing tool in the neuroscience field, by allowing optical control of neuronal activity with high cell-type specificity. The ability to activate or inhibit targeted neurons at millisecond resolution not only offers an investigative tool, but potentially also provides a therapeutic intervention strategy for acute correction of aberrant neuronal activity. As efficient therapeutic tools are in short supply for neurological disorders, optogenetic technology has therefore spurred considerable enthusiasm and fostered a new wave of translational studies in neuroscience. Epilepsy is among the disorders that have been widely explored. Partial epilepsies are characterized by seizures arising from excessive excitatory neuronal activity that emerges from a focal area. Based on the constricted seizure focus, it appears feasible to intercept partial seizures by acutely shutting down excitatory neurons by means of optogenetics. The availability of both inhibitory and excitatory optogenetic probes, along with the available targeting strategies for respective excitatory or inhibitory neurons, allows multiple conceivable scenarios for controlling abnormal circuit activity. Several such scenarios have been explored in the settings of experimental epilepsy and have provided encouraging translational findings and revealed interesting and unexpected new aspects of epileptogenesis. However, it has also emerged that considerable challenges persist before clinical translation becomes feasible. This review provides a general introduction to optogenetics, and an overview of findings that are relevant for understanding how optogenetics may be utilized therapeutically as a highly innovative treatment for epilepsy. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Partial validation of a French version of the ADHD-rating scale IV on a French population of children with ADHD and epilepsy. Factorial structure, reliability, and responsiveness.

PubMed

Mercier, Catherine; Roche, Sylvain; Gaillard, Ségolène; Kassai, Behrouz; Arzimanoglou, Alexis; Herbillon, Vania; Roy, Pascal; Rheims, Sylvain

2016-05-01

Attention deficit hyperactivity disorder (ADHD) is a well-known comorbidity in children with epilepsy. In English-speaking countries, the scores of the original ADHD-rating scale IV are currently used as main outcomes in various clinical trials in children with epilepsy. In French-speaking countries, several French versions are in use though none has been fully validated yet. We sought here for a partial validation of a French version of the ADHD-RS IV regarding construct validity, internal consistency (i.e., scale reliability), item reliability, and responsiveness in a group of French children with ADHD and epilepsy. The study involved 167 children aged 6-15years in 10 French neuropediatric units. The factorial structure and item reliability were assessed with a confirmatory factorial analysis for ordered categorical variables. The dimensions' internal consistency was assessed with Guttman's lambda 6 coefficient. The responsiveness was assessed by the change in score under methylphenidate and in comparison with a control group. The results confirmed the original two-dimensional factorial structure (inattention, hyperactivity/impulsivity) and showed a satisfactory reliability of most items, a good dimension internal consistency, and a good responsiveness of the total score and the two subscores. The studied French version of the ADHD-RS IV is thus validated regarding construct validity, reliability, and responsiveness. It can now be used in French-speaking countries in clinical trials of treatments involving children with ADHD and epilepsy. The full validation requires further investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

Adherence to outpatient epilepsy quality indicators at a tertiary epilepsy center

PubMed Central

Pourdeyhimi, R.; Wolf, B.J.; Simpson, A.N.; Martz, G.U.

2014-01-01

Introduction Quality indicators for the treatment of people with epilepsy were published in 2010. This is the first report of adherence to all measures in routine care of people with epilepsy at a level 4 comprehensive epilepsy center in the US. Methods Two hundred patients with epilepsy were randomly selected from the clinics of our comprehensive epilepsy center, and all visits during 2011 were abstracted for documentation of adherence to the eight quality indicators. Alternative measures were constructed to evaluate failure of adherence. Detailed descriptions of all equations are provided. Results Objective measures (EEG, imaging) showed higher adherence than counseling measures (safety). Initial visits showed higher adherence. Variations in the interpretation of the quality measure result in different adherence values. Advanced practice providers and physicians had different adherence patterns. No patient-specific patterns of adherence were seen. Discussion This is the first report of adherence to all the epilepsy quality indicators for a sample of patients during routine care in a level 4 epilepsy center in the US. Overall adherence was similar to that previously reported on similar measures. Precise definitions of adherence equations are essential for accurate measurement. Complex measures result in lower adherence. Counseling measures showed low adherence, possibly highlighting a difference between practice and documentation. Adherence to the measures as written does not guarantee high quality care. Conclusion The current quality indicators have value in the process of improving quality of care. Future approaches may be refined to eliminate complex measures and incorporate features linked to outcomes. PMID:25171260

Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex.

PubMed

Bernardo, Danilo; Nariai, Hiroki; Hussain, Shaun A; Sankar, Raman; Salamon, Noriko; Krueger, Darcy A; Sahin, Mustafa; Northrup, Hope; Bebin, E Martina; Wu, Joyce Y

2018-04-03

We aim to establish that interictal fast ripples (FR; 250-500 Hz) are detectable on scalp EEG, and to investigate their association to epilepsy. Scalp EEG recordings of a subset of children with tuberous sclerosis complex (TSC)-associated epilepsy from two large multicenter observational TSC studies were analyzed and compared to control children without epilepsy or any other brain-based diagnoses. FR were identified both by human visual review and compared with semi-automated review utilizing a deep learning-based FR detector. Seven out of 7 children with TSC-associated epilepsy had scalp FR compared to 0 out of 4 children in the control group (p = 0.003). The automatic detector has a sensitivity of 98% and false positive rate with average of 11.2 false positives per minute. Non-invasive detection of interictal scalp FR was feasible, by both visual and semi-automatic detection. Interictal scalp FR occurred exclusively in children with TSC-associated epilepsy and were absent in controls without epilepsy. The proposed detector achieves high sensitivity of FR detection; however, expert review of the results to reduce false positives is advised. Interictal FR are detectable on scalp EEG and may potentially serve as a biomarker of epilepsy in children with TSC. Copyright © 2018 International Federation of Clinical Neurophysiology. All rights reserved.

Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy.

PubMed

Fan, Zhiliang; Feng, Xiaojuan; Fan, Zhigang; Zhu, Xingyuan; Yin, Shaohua

2018-05-09

Epilepsy is a type of refractory neurologic disorder mental disease, which is associated with cognitive impairments and memory dysfunction. However, the potential mechanisms of epilepsy are not well understood. Previous evidence has identified the voltage gated potassium channel complex (VGKC) as a target in various cohorts of patients with epilepsy. In the present study, the efficacy of an antibody against VGKC (anti‑VGKC) for the treatment of epilepsy in mice was investigated. A mouse model of lithium‑pilocarpine temporal lobe epilepsy was established and anti‑VGKC treatment was administered for 30 days. Memory impairment, anxiety, visual attention, inhibitory control and neuronal loss were measured in the mouse model of lithium‑pilocarpine temporal lobe epilepsy. The results revealed that epileptic mice treated with anti‑VGKC were able to learn the task and presented attention impairment, even a tendency toward impulsivity and compulsivity. It was also exhibited that anti‑VGKC treatment decreased neuronal loss in structures classically associated with attentional performance in hippocampus. Mice who received Anti‑VGKC treatment had inhibited motor seizures and hippocampal damage as compared with control mice. In conclusion, these results indicated that anti‑VGKC treatment may present benefits for improvements of the condition of motor attention impairment and cognitive competence, which suggests that VGKC may be a potential target for the treatment of epilepsy.

Lacosamide add-on therapy for partial epilepsy.

PubMed

Weston, Jennifer; Shukralla, Arif; McKay, Andrew J; Marson, Anthony G

2015-06-16

Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on treatment with another drug. Sometimes multiple treatment combinations are tried to achieve maximum seizure control, although around a third of people do not achieve complete seizure control. Lacosamide is an antiepileptic drug that has been licensed as an add-on treatment for partial epilepsy. To evaluate the efficacy and tolerability of lacosamide when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (21 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL , The Cochrane Library Issue 4, April 2015), MEDLINE (Ovid, 1946 to 21 May 2015), Scopus (1823 to 13 November 2014), ClinicalTrials.gov (21 May 2015) and the WHO International Clinical Trials Registry Platform (ICTRP, 21 May 2015). We imposed no language restrictions. We contacted UCB (sponsors of lacosamide) and experts in the field. Randomised controlled trials of add-on lacosamide in people with drug-resistant partial epilepsy. Two review authors independently assessed trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal for any reason; and (4) adverse events. Primary analyses were intention-to-treat. Summary risk ratios were estimated for each outcome. We included three trials in our review (1311 participants), which were classified as having low risk of bias. All trials were placebo-controlled and assessed doses ranging from 200 mg to 600 mg per day. Trial duration ranged from 24 to 26 weeks. All trials used adequate methods of randomisation and were double-blind. Overall the quality of the evidence was rated as moderate to high. The overall risk ratio for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.70 (95% confidence interval (CI) 1.38 to 2.10); for seizure freedom for all doses of lacosamide compared with placebo was 2.50 (95% CI 0.85 to 7.34); and for treatment withdrawal for all doses of lacosamide compared with placebo was 1.88 (95% CI 1.40 to 2.52). Adverse effects significantly associated with lacosamide were abnormal co-ordination (risk ratio (RR) 6.12, 99% CI 1.35 to 27.77), diplopia (RR 5.29, 99% CI 1.97 to 14.23), dizziness (RR 3.53, 99% CI 2.20 to 5.68), nausea (RR 2.37, 99% CI 1.23 to 4.58) and vomiting (RR 3.49, 99% CI 1.43 to 8.54). Adverse effects that were not statistically significant were headache (RR 1.34, 99% CI 0.83 to 2.18), fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52) and somnolence (RR 1.44, 99% CI 0.67 to 3.09). This review has shown lacosamide to be effective and fairly well tolerated in the short term when used as add-on treatment for drug-resistant partial epilepsy in adults. Higher doses of lacosamide may be more associated with adverse effects and withdrawal of the drug than lower doses. Additional evidence on children is needed, and longer-term efficacy is unknown.

Psychosocial functioning in adolescents with complex partial seizures.

PubMed

Elliott, I

1992-03-01

This pilot study examined psychosocial functioning in adolescents (age 12.5-18.5 years) with complex partial seizures. Twenty-five subjects were divided into three groups: Group I (N = 11), medically treated with uncontrolled seizures; Group II (N = 6), medically managed with controlled seizures; and Group III (N = 8), epilepsy refractory to medical management with seizure control following surgery. Psychosocial functioning was measured using the "Adolescent Psychosocial Inventory" of Batzel and Dodrill. Findings revealed significant differences (F 4.80. p less than 0.02) in psychosocial functioning between the three groups. Group I showed the poorest overall adjustment; Group II, the best adjustment; Group III was better adjusted than Group I, but less than Group II. Significant difficulties were evident in the areas of school, interpersonal, emotional, seizure adjustment and overall psychosocial functioning in Group III. No problems were evident in Group II. School, emotional and overall adjustment were moderately problematic in Group III. Analysis of biological and demographic data revealed a significant association between increased numbers of medications and poorer psychosocial functioning (r = 58, p less than 0.02). The study results provide direction for clinic and community nurse specialists to set priorities with regard to assessment and supportive interventions.

Microencephaloceles: another dual pathology of intractable temporal lobe epilepsy in childhood.

PubMed

Aquilina, Kristian; Clarke, Dave F; Wheless, James W; Boop, Frederick A

2010-04-01

Temporal lobe encephaloceles can be associated with temporal lobe epilepsy. The authors report on the case of an adolescent with multiple microencephaloceles, in the anterolateral middle fossa floor, identified at surgery (temporal lobectomy) for intractable partial-onset seizures of temporal origin. Magnetic resonance imaging revealed only hippocampal atrophy. Subdural electrodes demonstrated ictal activity arising primarily from the anterior and lateral temporal lobe, close to the microencephaloceles, spreading to the anterior and posterior mesial structures. Pathological examination revealed diffuse temporal gliosis involving the hippocampus, together with microdysgenesis of the amygdala. The literature on epilepsy secondary to encephaloceles is reviewed and the contribution of the microencephaloceles to the seizure disorder in this patient is discussed.

[Lacosamide: a new generation in the treatment of epilepsy].

PubMed

Gil-Nagel, A; Marin, H

2011-02-01

Despite the large number of antiepileptic drugs (AED) available today, more than 30% of patients with epilepsy do not manage to achieve adequate control over their seizures. For patients, the administration of the latest AED can be a good alternative, prior to surgery or when there are contraindications against it. Third generation AED offer different mechanisms of action and tolerability profiles that are more favourable than those of the first and second generations. Lacosamide has recently been approved by the European Medicines Agency (EMEA) and its United States counterpart (FDA) as an adjuctive AED in partial onset seizures in adults over the age of 16, thus making it a novel option in the treatment of epilepsy.

Genetic linkage studies in familial partial epilepsy: Exclusion of the human chromosome regions syntenic to the El-1 mouse locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopes-Cendes, I.; Mulley, J.C.; Andermann, E.

1994-09-01

Recently, six families with a familial form of partial epilepsy were described. All pedigrees showed autosomal dominant inheritance with incomplete penetrance. Affected individuals present with predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse chromosome 9. Comparative genetic maps between man and mouse have been used for prediction of localization of several human disease genes. Because the region ofmore » mouse chromosome 9 that is the most likely to contain the El-1 locus is syntenic to regions on human chromosomes 3q21-p22, 3q21-q23.3, 6q12 and 15q24, we adopted the candidate gene approach as an initial linkage strategy. Twenty-two polymorphic microsatellite markers covering these regions were used for genotyping individuals in the three larger families ascertained, two of which are Australian and one French-Canadian. Negative two-point lod scores were obtained separately for each family. The analysis of all three families combined significantly excludes the candidate regions on chromosomes 3, 6 and 15.« less

Epilepsy in twins: insights from unique historical data of William Lennox.

PubMed

Vadlamudi, L; Andermann, E; Lombroso, C T; Schachter, S C; Milne, R L; Hopper, J L; Andermann, F; Berkovic, S F

2004-04-13

To classify the Lennox twin pairs according to modern epilepsy classifications, use the classic twin model to identify which epilepsy syndromes have an inherited component, search for evidence of syndrome-specific genes, and compare concordances from Lennox's series with a contemporary Australian series. Following review of Lennox's original files describing twins with seizures from 1934 through 1958, the International League Against Epilepsy classifications of seizures and epileptic syndromes were applied to 169 pairs. Monozygous (MZ) and dizygous (DZ) pairs were subdivided into epilepsy syndromes and casewise concordances estimated. The authors excluded 26 pairs, with 71 MZ and 72 DZ pairs remaining. Seizure analysis demonstrated strong parallels between contemporary seizure classification and Lennox's terminology. Epilepsy syndrome diagnoses were made in 75%. The MZ and DZ casewise concordance estimates gave strong evidence for a major genetic influence in idiopathic generalized epilepsies (0.80 versus 0.00; n = 23). High MZ casewise concordances also supported a genetic etiology in symptomatic generalized epilepsies and febrile seizures. The pairs who were concordant for seizures usually had the same syndromic diagnoses in both twins (86% in MZ, 60% in DZ), suggesting syndrome-specific genes. Apart from partial epilepsies, the MZ casewise concordances were similar to those derived from Australian twin data. The authors were able to apply contemporary classifications to Lennox's twins. The data confirm genetic bases for common generalized epilepsies as well as febrile seizures and provide further support for syndrome-specific genes. Finally, comparable results to our Australian series were obtained, verifying the value of twin studies.

Peri-ictal water drinking and other ictal vegetative symptoms: Localizing and lateralizing the epileptogenic zone in temporal lobe epilepsy? Two case reports and review of the literature.

PubMed

Errguig, L; Lahjouji, F; Belaidi, H; Jiddane, M; Elkhamlichi, A; Dakka, T; Ouazzani, R

2013-11-01

Peri-ictal behavior disorders can be helpful in localizing and lateralizing seizure onset in partial epilepsies, especially those originating in the temporal lobe. In this paper, we present the case of two right-handed women aged 36 and 42 years who presented with partial seizures of mesial temporal type. Both of the patients had drug resistant epilepsy and undergone presurgical evaluation tests including brain magnetic resonance imaging, video-EEG monitoring and neuropsychological testing. The two patients had hippocampal sclerosis in the right temporal lobe and exhibited PIWD behavior concomitant with right temporal lobe discharges documented during video-EEG recordings. Anterior temporal lobectomy was performed in one case with an excellent outcome after surgery. The patient was free of seizures at 3 years follow-up. We reviewed other publications of peri-ictal autonomic symptoms considered to have a lateralizing significance, such as peri-ictal vomiting, urinary urge, ictal pilo-erection. Clinicians should search for these symptoms, even if not spontaneously reported by the patient, because they are often under-estimated, both by the patients themselves and by physicians. Additionally, patients with lateralizing auras during seizures have a significantly better outcome after epilepsy surgery than those without lateralizing features. Copyright © 2013. Published by Elsevier Masson SAS.

Consensus Guidelines into the Management of Epilepsy in Adults with an Intellectual Disability

ERIC Educational Resources Information Center

Kerr, M.; Scheepers, M.; Arvio, M.; Beavis, J.; Brandt, C.; Brown, S.; Huber, B.; Iivanainen, M.; Louisse, A. C.; Martin, P.; Marson, A. G.; Prasher, V.; Singh, B. K.; Veendrick, M.; Wallace, R. A.

2009-01-01

Background: Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. Results: A Delphi process identified a list…

Mitochondrial Causes of Epilepsy: Evaluation, Diagnosis, and Treatment.

PubMed

Steele, Hannah E; Chinnery, Patrick F

2015-06-01

Mitochondrial disorders are frequently associated with seizures. In this review, the authors discuss the seizure patterns and distinguishing features of mitochondrial epilepsy, alongside the indications for investigating, and how to investigate epilepsy from a mitochondrial perspective. Finally, they discuss management strategies for this complex group of patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Brain Inflammation in Epileptogenesis in TSC

DTIC Science & Technology

2013-07-01

and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy . Neurobiol...tissue obtained from epilepsy patients, such as with mesial temporal sclerosis. Different types of inflammatory mediators and pathways have been...13. SUPPLEMENTARY NOTES 14. ABSTRACT Epilepsy is a common, disabling problem in patients with tuberous sclerosis complex (TSC) and

Clinic-friendly screening for cognitive and mental health problems in school-aged youth with epilepsy.

PubMed

Asato, Miya R; Doss, Julia L; Plioplys, Sigita

2015-07-01

Cognitive, psychiatric, psychosocial, and behavioral difficulties are common in youth with epilepsy. Collectively, these comorbidities can be referred to as mental health problems as they reflect brain and behavioral function. Detection and treatment of mental health problems remain an unmet need in epilepsy care that can impact epilepsy, psychosocial, scholastic, and quality-of-life outcomes. Given limited resources in everyday pediatric epilepsy practice, this targeted review provides a stratified plan and suggested tools for screening school-aged youth with epilepsy for the presence of mental health problems. Comanagement of epilepsy and associated comorbidities is a newer concept that may help address the complex, long-term needs of patients by using a multidisciplinary team approach and by engaging primary care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

Phenomenology of hallucinations, illusions, and delusions as part of seizure semiology.

PubMed

Kasper, B S; Kasper, E M; Pauli, E; Stefan, H

2010-05-01

In partial epilepsy, a localized hypersynchronous neuronal discharge evolving into a partial seizure affecting a particular cortical region or cerebral subsystem can give rise to subjective symptoms, which are perceived by the affected person only, that is, ictal hallucinations, illusions, or delusions. When forming the beginning of a symptom sequence leading to impairment of consciousness and/or a classic generalized seizure, these phenomena are referred to as an epileptic aura, but they also occur in isolation. They often manifest in the fully awake state, as part of simple partial seizures, but they also can be associated to different degrees of disturbed consciousness. Initial ictal symptoms often are closely related to the physiological functions of the cortical circuit involved and, therefore, can provide localizing information. When brain regions related to sensory integration are involved, the seizure discharge can cause specific kinds of hallucinations, for example, visual, auditory, gustatory, olfactory, and cutaneous sensory sensations. In addition to these elementary sensory perceptions, quite complex hallucinations related to a partial seizure can arise, for example, perception of visual scenes or hearing music. By involving psychic and emotional spheres of human perception, many seizures also give rise to hallucinatory emotional states (e.g., fear or happiness) or even more complex hallucinations (e.g., visuospatial phenomena), illusions (e.g., déjà vu, out-of-body experience), or delusional beliefs (e.g., identity change) that often are not easily recognized as epileptic. Here we suggest a classification into elementary sensory, complex sensory, and complex integratory seizure symptoms. Epileptic hallucinations, illusions, and delusions shine interesting light on the physiology and functional anatomy of brain regions involved and their functions in the human being. This article, in which 10 cases are described, introduces the fascinating phenomenology of subjective seizure symptoms. Copyright (c) 2010 Elsevier Inc. All rights reserved.

[Building epilepsy care network in Japan].

PubMed

Otsuki, Taisuke

2012-01-01

Number of epilepsy patient in Japan officially surveyed by our government in 2008 is 219,000, which is only 0.17% of the total population and less than one third of the prevalence rate reported in Western countries. Number of epilepsy surgery per year in Japan is also low and less than half of other countries such as US, UK and Korea. These numbers may suggest that epilepsy care in Japan is not sufficient to cover all hidden medical needs of people with epilepsy at present. To solve this issue, our research group funded by the government have started to build an epilepsy care network among primary care physicians, secondary care neurology specialists and tertiary care epilepsy centers by utilizing a web site: Epilepsy Care Network-Japan (http://www.ecn-japan.com/) from July 2012. We are also proposing an epilepsy care algorithm suitable for our complex medical community consisted with various neurology specialists such as pediatric and adult neurologists, neurosurgeons and psychiatrists. Building Epilepsy Care Network in Japan may facilitate better medical and social support for people with epilepsy in Japan.

Cost-utility analysis of competing treatment strategies for drug-resistant epilepsy in children with Tuberous Sclerosis Complex.

PubMed

Fallah, Aria; Weil, Alexander G; Wang, Shelly; Lewis, Evan; Baca, Christine B; Mathern, Gary W

2016-10-01

The management of drug-resistant epilepsy in children with Tuberous Sclerosis Complex (TSC) is challenging because of the multitude of treatment options, wide range of associated costs, and uncertainty of seizure outcomes. The most cost-effective approach for children whose epilepsy has failed to improve with first-line medical therapy is uncertain. A review of MEDLINE from 1990 to 2015 was conducted. A cost-utility analysis, from a third-party payer perspective, was performed for children with drug-resistant epilepsy that had failed to improve with 2 antiseizure drugs (ASDs) and that was amenable to resective epilepsy surgery, across a time-horizon of 5years. Four strategies were included: (1) resective epilepsy surgery, (2) vagus nerve stimulator (VNS) implantation, (3) ketogenic diet, and (4) addition of a third ASD (specifically, carbamazepine). The incremental cost per quality-adjusted life year (QALY) gained was analyzed. Given a willingness-to-pay (WTP) of $100,000 per QALY, the addition of a third ASD ($6600 for a gain of 4.14 QALYs) was the most cost-effective treatment strategy. In a secondary analysis, if the child whose epilepsy had failed to improve with 3 ASDs, ketogenic diet, addition of a fourth ASD, and resective epilepsy surgery were incrementally cost-effective treatment strategies. Vagus nerve stimulator implantation was more expensive yet less effective than alternative strategies and should not be prioritized. The addition of a third ASD is a universally cost-effective treatment option in the management of children with drug-resistant epilepsy that has failed to improve with 2 ASDs. For children whose epilepsy has failed to improve with 3 ASDs, the most cost-effective treatment depends on the health-care resources available reflected by the WTP. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of an Epilepsy Nursing Communication Tool: Improving the Quality of Interactions Between Nurses and Patients With Seizures

PubMed Central

Buelow, Janice; Miller, Wendy; Fishman, Jesse

2018-01-01

ABSTRACT Background: Nurses have become increasingly involved in overseeing the management of patients with complex medical conditions, including those with epilepsy. Nurses who are not specialists in epilepsy can play a central role in providing optimal care, education, and support to their patients with epilepsy, given the proper tools. Objective: Our objective was to create a tool that can be used by nurses in the clinic setting to help facilitate discussion of topics relevant to enhancing medical care and management of patients with epilepsy. To address this need, a panel of epilepsy nursing experts used a patient-centered care approach to develop an Epilepsy Nursing Communication Tool (ENCT). Methods: An initial set of topics and questions was created based on findings from a literature review. Eight nurse experts reviewed and revised the ENCT using focus groups and discussion forums. The revised ENCT was provided to nurses who care for patients with epilepsy but had not been involved in ENCT development. Nurses were asked to rate the usability and feasibility on a 5-point scale to assess whether the tool captured important topics and was easy to use. Results: Ten nurses provided usability and feasibility assessments. Results indicated strong tool utility, with median scores of 4.5, 4, and 4 for usefulness, ease of use, and acceptability, respectively. Conclusions: The preliminary ENCT shows promise in providing a tool that nurses can use in their interactions with patients with epilepsy to help address the complexity of disease management, which may help improve overall patient care. PMID:29505437

Adherence to outpatient epilepsy quality indicators at a tertiary epilepsy center.

PubMed

Pourdeyhimi, R; Wolf, B J; Simpson, A N; Martz, G U

2014-10-01

Quality indicators for the treatment of people with epilepsy were published in 2010. This is the first report of adherence to all measures in routine care of people with epilepsy at a level 4 comprehensive epilepsy center in the US. Two hundred patients with epilepsy were randomly selected from the clinics of our comprehensive epilepsy center, and all visits during 2011 were abstracted for documentation of adherence to the eight quality indicators. Alternative measures were constructed to evaluate failure of adherence. Detailed descriptions of all equations are provided. Objective measures (EEG, imaging) showed higher adherence than counseling measures (safety). Initial visits showed higher adherence. Variations in the interpretation of the quality measure result in different adherence values. Advanced practice providers and physicians had different adherence patterns. No patient-specific patterns of adherence were seen. This is the first report of adherence to all the epilepsy quality indicators for a sample of patients during routine care in a level 4 epilepsy center in the US. Overall adherence was similar to that previously reported on similar measures. Precise definitions of adherence equations are essential for accurate measurement. Complex measures result in lower adherence. Counseling measures showed low adherence, possibly highlighting a difference between practice and documentation. Adherence to the measures as written does not guarantee high quality care. The current quality indicators have value in the process of improving quality of care. Future approaches may be refined to eliminate complex measures and incorporate features linked to outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic Forms of Epilepsies and other Paroxysmal Disorders

PubMed Central

Olson, Heather E.; Poduri, Annapurna; Pearl, Phillip L.

2016-01-01

Genetic mechanisms explain the pathophysiology of many forms of epilepsy and other paroxysmal disorders such as alternating hemiplegia of childhood, familial hemiplegic migraine, and paroxysmal dyskinesias. Epilepsy is a key feature of well-defined genetic syndromes including Tuberous Sclerosis Complex, Rett syndrome, Angelman syndrome, and others. There is an increasing number of singe gene causes or susceptibility factors associated with several epilepsy syndromes, including the early onset epileptic encephalopathies, benign neonatal/infantile seizures, progressive myoclonus epilepsies, genetic generalized and benign focal epilepsies, epileptic aphasias, and familial focal epilepsies. Molecular mechanisms are diverse, and a single gene can be associated with a broad range of phenotypes. Additional features, such as dysmorphisms, head size, movement disorders, and family history may provide clues to a genetic diagnosis. Genetic testing can impact medical care and counseling. We discuss genetic mechanisms of epilepsy and other paroxysmal disorders, tools and indications for genetic testing, known genotype-phenotype associations, the importance of genetic counseling, and a look towards the future of epilepsy genetics. PMID:25192505

Epilepsy

MedlinePlus

... focal) seizures: This type of seizure affects only one part of the brain. The symptoms may vary, depending on where in the brain the seizure starts. For example, a partial seizure may cause changes in emotions, ...

Management of psychiatric and neurological comorbidities in epilepsy.

PubMed

Kanner, Andres M

2016-02-01

The treatment of epileptic seizure disorders is not restricted to the achievement of seizure-freedom, but must also include the management of comorbid medical, neurological, psychiatric and cognitive comorbidities. Psychiatric and neurological comorbidities are relatively common and often co-exist in people with epilepsy (PWE). For example, depression and anxiety disorders are the most common psychiatric comorbidities in PWE, and they are particularly common in PWE who also have a neurological comorbidity, such as migraine, stroke, traumatic brain injury or dementia. Moreover, psychiatric and neurological comorbodities often have a more severe impact on the quality of life in patients with treatment-resistant focal epilepsy than do the actual seizures. Epilepsy and psychiatric and neurological comorbidities have a complex relationship, which has a direct bearing on the management of both seizures and the comorbidities: the comorbidities have to be factored into the selection of antiepileptic drugs, and the susceptibility to seizures has to be considered when choosing the drugs to treat comorbidities. The aim of this Review is to highlight the complex relationship between epilepsy and common psychiatric and neurological comorbidities, and provide an overview of how treatment strategies for epilepsy can positively and negatively affect these comorbidities and vice versa.

Ipsiversive ictal eye deviation in inferioposterior temporal lobe epilepsy-Two SEEG cases report.

PubMed

Zhang, Wei; Liu, Xingzhou; Zuo, Lijun; Guo, Qiang; Chen, Qi; Wang, Yongjun

2017-02-21

Versive seizure characterized by conjugate eye movement during epileptic seizure has been considered commonly as one of the most valuable semiological signs for epilepsy localization, especially for frontal lobe epilepsy. However, the lateralizing and localizing significance of ictaleye deviation has been questioned by clinical observation of a series of focal epilepsy studies, including frontal, central, temporal, parietal and occipital epilepsy. Two epileptic cases characterized by ipsiversive eye deviation as initial clinical sign during the habitual epileptic seizures are presented in this paper. The localization of the epileptogenic zone of both of the cases has been confirmed as inferioposterior temporal region by the findings of ictalstereoelectroencephalography (SEEG) and a good result after epileptic surgery. Detailed analysis of the exact position of the key contacts of the SEEG electrodes identified the overlap between the location of the epileptogenic zone and human MT/MST complex, which play a crucial role in the control of smooth pursuit eye movement. Ipsiversive eye deviation could be the initial clinical sign of inferioposterior temporal lobe epilepsy and attribute to the involvement of human MT/MST complex, especially human MST whichwas located on the anterior/dorsal bank of the anterior occipital sulcus (AOS).

Psychopathology in pediatric epilepsy: role of antiepileptic drugs.

PubMed

Caplan, Rochelle

2012-01-01

Children with epilepsy are usually treated with antiepileptic drugs (AEDS). Some AEDs adversely affect behavior in susceptible children. Since psychiatric comorbidity is prevalent in pediatric epilepsy, this paper attempts to disentangle these AED side effects from the psychopathology associated with this illness. It first outlines the clinical and methodological problems involved in determining if AEDs contribute to the behavior and emotional problems of children with epilepsy. It then presents research evidence for and against the role AEDs play in the psychopathology of children with epilepsy, and outlines how future studies might investigate this problem. A brief description of how to clinically separate out AED effects from the complex illness-related and psychosocial factors that contribute to the behavior difficulties of children with epilepsy concludes the paper.

Tissue Expressions of Soluble Human Epoxide Hydrolase-2 Enzyme in Patients with Temporal Lobe Epilepsy.

PubMed

Ahmedov, Merdin Lyutviev; Kemerdere, Rahsan; Baran, Oguz; Inal, Berrin Bercik; Gumus, Alper; Coskun, Cihan; Yeni, Seher Naz; Eren, Bulent; Uzan, Mustafa; Tanriverdi, Taner

2017-10-01

We sought to simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. The temporal cortex in the epilepsy patients had a significantly higher enzyme level than did the temporal cortex of the control group (P = 0.03). Correlation analysis showed that as the enzyme level increases in the temporal cortex, it also increases in the hippocampal complex (r 2  = 0.06, P = 0.00001). More important, enzyme tissue levels showed positive correlations with seizure frequency in both the temporal cortex and hippocampal complex in patients (r 2  = 0.7, P = 0.00001 and r 2  = 0.4, P = 0.003, respectively). The duration of epilepsy was also positively correlated with the hippocampal enzyme level (r 2  = 0.06, P = 0.00001). Soluble human epoxy hydrolase enzyme-2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuroinflammation in experimental epilepsy models in the current literature. Copyright © 2017 Elsevier Inc. All rights reserved.

The Epidemiology of Global Epilepsy.

PubMed

Singh, Anuradha; Trevick, Stephen

2016-11-01

The International League Against Epilepsy defines epilepsy as at least 2 unprovoked seizures more than 24 hours apart. It is a wide-reaching and complex illness affecting more than 70 million people worldwide and can take on a variety of forms, patterns, and severities. Geographic differences in the illness are often related to its etiology. A host of endemic illnesses and parasitic infections can lead to epilepsy syndromes. Management varies by region due to the availability of diagnostic modalities and medications. Treatment gaps in epilepsy care often are related to social and cultural factors that must also be understood. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of lacosamide on cognition, quality-of-life measures, and quality of life in patients with refractory partial epilepsy.

PubMed

Lancman, Marcelo E; Fertig, Evan J; Trobliger, Robert W; Perrine, Kenneth; Myers, Lorna; Iyengar, Sloka S; Malik, Munazza

2016-08-01

The objective of this study was to examine cognitive and quality-of-life measures/quality of life outcomes with adjunctive lacosamide therapy in patients with treatment-resistant partial epilepsy. This was a prospective, open-label, nonblinded, adjunctive therapy test-retest (within subjects) study of patients with treatment-resistant partial epilepsy in which outcome (cognitive functioning and mood/quality of life) was measured in the same subject before and after adjunctive lacosamide administration for 24weeks. The cognitive assessment included the following: Controlled Oral Word Association Test, Buschke Selective Reminding Test, Brief Visuospatial Memory Test-Revised, Stroop Color Word Test, Symbol Digit Modalities Test, Digit Span, Digit Cancellation, and Trails A and B. The quality-of-life measures/quality-of-life assessment included the following: Beck Depression Inventory-II, Profile of Mood States, and Quality of Life Inventory-89. Lacosamide was started at 100mg (50mg twice daily) and could be titrated as needed up to 400mg/day (200mg twice daily). Baseline concomitant AEDs were kept constant. Composite scores were calculated for a pre-post difference score for the cognitive and mood/quality-of-life measures separately and used in regression analyses to correct for the effects of age, education, seizure frequency, seizure severity, dose of lacosamide, and number of AEDs at baseline. Thirty-four patients were enrolled (13 males, 21 females). Mean age was 38.8±2.43years. Mean seizure frequency decreased significantly from 2.0±2.55 seizures per week at baseline to 1.02±1.72 seizures per week at posttreatment (t=4.59, p<.0001) with a 50% responder rate seen in 18 patients (52.9%). No significant differences were found on the composite scores of the cognitive or the mood/quality-of-life measures after 6months of lacosamide. Lacosamide appeared to have low risks of significant changes in cognition or mood/quality of life. In addition, the present study supports prior studies that have proven lacosamide as an effective adjunctive therapy for the treatment of resistant partial epilepsy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis.

PubMed

Vanhaesebrouck, An E; Posch, Barbara; Baker, Sam; Plessas, Ioannis N; Palmer, Anthony C; Constantino-Casas, Fernando

2012-12-01

A 14-year-old male domestic shorthair cat presented with an acute onset of aggressive behaviour, fear and hypersalivation. Neurological examination revealed bilateral mydriasis and left-sided facial twitching and hemiparesis. Magnetic resonance imaging (MRI) showed moderate bilateral symmetrical T2-hyperintensity along the entire hippocampus and bilateral asymmetric T2-hyperintensity in the pyriform lobes. Marked bilateral contrast enhancement of the hippocampus was evident on post-contrast T1-weighted images. The partial complex seizures were refractory to medical treatment and the cat was euthanased 4 days after admission. The clinical and MRI findings were consistent with feline hippocampal necrosis (FHN). On histopathology, neuronal necrosis and astrocytosis were present in the hippocampi and pyriform lobes. In addition, an oligodendroglioma was detected in the right pyriform lobe. Contrary to previous reports of FHN in which no underlying cause could be identified, we believe that in this case the seizure focus arose from a neoplastic lesion within the right pyriform lobe. This unique case report represents the so-called 'dual pathology' of temporal lobe epilepsy in humans, in which an extrahippocampal lesion within the temporal lobe results in hippocampal sclerosis.

Long-term add-on pregabalin treatment in patients with partial-onset epilepsy: pooled analysis of open-label clinical trials.

PubMed

Uthman, Basim M; Bazil, Carl W; Beydoun, Ahmad; Schulze-Bonhage, Andreas; Benabou, Reina; Whalen, Ed; Emir, Birol; Griesing, Teresa; Leon, Teresa

2010-06-01

To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59% completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was >or=300 mg/day; over half took >or=450 mg/day. There was a mean reduction in the 28-day seizure rate of 25-40%, and more than 40% of all patients had a >or=50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6% were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up.

Childhood epilepsy: a critical review of cost-of-illness studies.

PubMed

Argumosa, Ana; Herranz, Josè Luis

2004-03-01

Epilepsy is an illness with multiple consequences and costs for children, families and society. There are only a few studies published on the cost of childhood epilepsy. The different methodologies used in these studies make it difficult to compare them or even to compare the cost of childhood epilepsy treatment with that of adult epilepsy. Nevertheless, studies highlight important differences in the distribution of costs associated with childhood epilepsy and epilepsy in adults. It is understandable that direct costs represent the higher percentage of the total cost associated with childhood epilepsy treatment, given the higher number of hospital admissions and investigations, as well as the complexity of therapeutic trials, while indirect costs represent the greater proportion in adult epilepsy treatment. In addition to age, the total cost associated with epilepsy also depends on other factors such as seizure frequency, the moment at which the illness cost is estimated and the local health care system. In summary, chronic illnesses not only have an influence on the physical and psychological development of children, they also impose costs on the family and society. Childhood epilepsy has greater economic costs than those generated by more prevalent, chronic illnesses.

IgG and complement deposition and neuronal loss in cats and humans with epilepsy and voltage-gated potassium channel complex antibodies.

PubMed

Klang, Andrea; Schmidt, Peter; Kneissl, Sibylle; Bagó, Zoltán; Vincent, Angela; Lang, Bethan; Moloney, Teresa; Bien, Christian G; Halász, Péter; Bauer, Jan; Pákozdy, Akos

2014-05-01

Voltage-gated potassium channel complex (VGKC-complex) antibody (Ab) encephalitis is a well-recognized form of limbic encephalitis in humans, usually occurring in the absence of an underlying tumor. The patients have a subacute onset of seizures, magnetic resonance imaging findings suggestive of hippocampal inflammation, and high serum titers of Abs against proteins of the VGKC-complex, particularly leucine-rich, glioma-inactivated 1 (LGI1). Most patients are diagnosed promptly and recover substantially with immunotherapies; consequently, neuropathological data are limited. We have recently shown that feline complex partial cluster seizures with orofacial involvement (FEPSO) in cats can also be associated with Abs against VGKC-complexes/LGI1. Here we examined the brains of cats with FEPSO and compared the neuropathological findings with those in a human with VGKC-complex-Ab limbic encephalitis. Similar to humans, cats with VGKC-complex-Ab and FEPSO have hippocampal lesions with only moderate T-cell infiltrates but with marked IgG infiltration and complement C9neo deposition on hippocampal neurons, associated with neuronal loss. These findings provide further evidence that FEPSO is a feline form of VGKC-complex-Ab limbic encephalitis and provide a model for increasing understanding of the human disease.

Prioritization of Epilepsy Associated Candidate Genes by Convergent Analysis

PubMed Central

Jia, Peilin; Ewers, Jeffrey M.; Zhao, Zhongming

2011-01-01

Background Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research. Methodology/Principal Findings In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways. Conclusions/Significance The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases. PMID:21390307

Prioritization of epilepsy associated candidate genes by convergent analysis.

PubMed

Jia, Peilin; Ewers, Jeffrey M; Zhao, Zhongming

2011-02-24

Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research. In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways. The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases.

Correlation of EEG with neuropsychological status in children with epilepsy.

PubMed

Hsu, David A; Rayer, Katherine; Jackson, Daren C; Stafstrom, Carl E; Hsu, Murielle; Ferrazzano, Peter A; Dabbs, Kevin; Worrell, Gregory A; Jones, Jana E; Hermann, Bruce P

2016-02-01

To determine correlations of the EEG frequency spectrum with neuropsychological status in children with idiopathic epilepsy. Forty-six children ages 8-18 years old with idiopathic epilepsy were retrospectively identified and analyzed for correlations between EEG spectra and neuropsychological status using multivariate linear regression. In addition, the theta/beta ratio, which has been suggested as a clinically useful EEG marker of attention-deficit hyperactivity disorder (ADHD), and an EEG spike count were calculated for each subject. Neuropsychological status was highly correlated with posterior alpha (8-15 Hz) EEG activity in a complex way, with both positive and negative correlations at lower and higher alpha frequency sub-bands for each cognitive task in a pattern that depends on the specific cognitive task. In addition, the theta/beta ratio was a specific but insensitive indicator of ADHD status in children with epilepsy; most children both with and without epilepsy have normal theta/beta ratios. The spike count showed no correlations with neuropsychological status. (1) The alpha rhythm may have at least two sub-bands which serve different purposes. (2) The theta/beta ratio is not a sensitive indicator of ADHD status in children with epilepsy. (3) The EEG frequency spectrum correlates more robustly with neuropsychological status than spike count analysis in children with idiopathic epilepsy. (1) The role of posterior alpha rhythms in cognition is complex and can be overlooked if EEG spectral resolution is too coarse or if neuropsychological status is assessed too narrowly. (2) ADHD in children with idiopathic epilepsy may involve different mechanisms from those in children without epilepsy. (3) Reliable correlations with neuropsychological status require longer EEG samples when using spike count analysis than when using frequency spectra. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Hormonal Aspects of Epilepsy

PubMed Central

Pennell, Page B.

2009-01-01

Synopsis The interactions between hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions which affect both men and women in various ways. Abnormalities of baseline endocrine status occur more commonly in people with epilepsy, and are most often described for the sex steroid hormone axis. Common symptoms include sexual dysfunction, decreased fertility, premature menopause, and polycystic ovarian syndrome. Antiepileptic drugs and hormones have a bidirectional interaction, with a decrease in the efficacy of hormonal contraceptive agents with some AEDs and a decrease in the concentration and efficacy of other AEDs with hormonal contraceptives. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy. However, this knowledge can be used to develop hormonal strategies to improve seizure control in people with epilepsy. PMID:19853217

Lack of antibodies to NMDAR or VGKC-complex in GAD and cardiolipin antibody-positive refractory epilepsy.

PubMed

Liimatainen, Suvi; Peltola, Jukka; Hietaharju, Aki; Sabater, Lidia; Lang, Bethan

2014-03-01

Over the last few years autoantibodies against neuronal proteins have been identified in several forms of autoimmune encephalitis and epilepsy. NMDA receptor (NMDAR) and voltage gated potassium channel (VGKC) complex antibodies are mainly associated with limbic encephalitis (LE) whereas glutamic acid decarboxylase antibodies (GADA) and anticardiolipin (ACL) antibodies are more commonly detected in patients with chronic epilepsy. Clinical features vary between these antibodies suggesting the specificity of different neuronal antibodies in seizures. Serum samples of 14 GADA positive and 24 ACL positive patients with refractory epilepsy were analyzed for the presence of VGKC or NMDAR antibodies. No positive VGKC or NMDAR antibodies were found in these patients. The results confirm the different significance of these neuronal antibodies in seizure disorders. Different autoantibodies have different significance in seizures and probably have different pathophysiological mechanisms of actions. Copyright © 2014 Elsevier B.V. All rights reserved.

Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy

PubMed Central

Witt, Thomas; Worth, Robert; Henry, Thomas R.; Gross, Robert E.; Nazzaro, Jules M.; Labar, Douglas; Sperling, Michael R.; Sharan, Ashwini; Sandok, Evan; Handforth, Adrian; Stern, John M.; Chung, Steve; Henderson, Jaimie M.; French, Jacqueline; Baltuch, Gordon; Rosenfeld, William E.; Garcia, Paul; Barbaro, Nicholas M.; Fountain, Nathan B.; Elias, W. Jeffrey; Goodman, Robert R.; Pollard, John R.; Tröster, Alexander I.; Irwin, Christopher P.; Lambrecht, Kristin; Graves, Nina; Fisher, Robert

2015-01-01

Objective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy. Methods: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion. Seizure frequency was determined using daily seizure diaries. Results: The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001). Conclusion: Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population. Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years. PMID:25663221

Oxcarbazepine for refractory epilepsy: systematic review of the literature.

PubMed

Saconato, Humberto; Prado, Gilmar Fernandes do; Puga, Maria Eduarda dos Santos; Atallah, Alvaro Nagib

2009-01-01

It has been estimated that 50 million people worldwide suffer from epilepsy and around 30% will not achieve adequate control over the disease. The aim was to evaluate the effectiveness of oxcarbazepine for refractory partial or generalized epilepsy. Systematic review. A search was conducted in the PubMed, Lilacs, EMBASE and CENTRAL databases. Studies were analyzed using the Cochrane Collaboration methodology. Four randomized clinical trials of medium to poor methodological quality were included. Among the adult patients, the chances that they would obtain a 50% reduction in seizure frequency were greater after using oxcarbazepine at doses of 600 mg (relative risk, RR 2.11; 95% confidence interval, CI 1.32 to 3.35), 1,200 mg (RR 3.24; 95% CI 2.11 to 4.98) and 2,400 mg (RR 3.83; 95% CI 2.59 to 5.97). Among the children, the response in the group using oxcarbazepine was also greater (RR 2.11; 95% CI 1.32 to 3.35). The oxcarbazepine doses of 1,200 mg (RR 17.59; 95% CI 2.37 to 130.35) and 2,400 mg (RR 25.41; 95% CI 6.26 to 103.10) were effective for keeping patients probably free from seizures, but the dose of 600 mg was not. There was no significant difference between oxcarbazepine and carbamazepine for controlling the crises. There is moderate evidence indicating that oxcarbazepine is effective as an alternative treatment for partial or generalized epilepsy in children and adults who were refractory to previous treatment.

Peri-ictal ECG changes in childhood epilepsy: implications for detection systems.

PubMed

Jansen, Katrien; Varon, Carolina; Van Huffel, Sabine; Lagae, Lieven

2013-10-01

Early detection of seizures could reduce associated morbidity and mortality and improve the quality of life of patients with epilepsy. In this study, the aim was to investigate whether ictal tachycardia is present in focal and generalized epileptic seizures in children. We sought to predict in which type of seizures tachycardia can be identified before actual seizure onset. Electrocardiogram segments in 80 seizures were analyzed in time and frequency domains before and after the onset of epileptic seizures on EEG. These ECG parameters were analyzed to find the most informative ones that can be used for seizure detection. The algorithm of Leutmezer et al. was used to find the temporal relationship between the change in heart rate and seizure onset. In the time domain, the mean RR shows a significant difference before compared to after onset of the seizure in focal seizures. This can be observed in temporal lobe seizures as well as frontal lobe seizures. Calculation of mean RR interval has a high specificity for detection of ictal heart rate changes. Preictal heart rate changes are observed in 70% of the partial seizures. Ictal heart rate changes are present only in partial seizures in this childhood epilepsy study. The changes can be observed in temporal lobe seizures as well as in frontal lobe seizures. Heart rate changes precede seizure onset in 70% of the focal seizures, making seizure detection and closed-loop systems a possible therapeutic alternative in the population of children with refractory epilepsy. © 2013.

[Validation of the Spanish version of the QOLIE-10 quality of life in epilepsy questionnaire].

PubMed

Viteri, C; Codina, M; Cobaleda, S; Lahuerta, J; Barriga, J; Barrera, S; Morales, M D

2008-04-01

Epilepsy patients not only have to deal with the disease itself but also the side effects of some treatments, fear about sudden occurrence of seizures, stigmatization, and restrictions in activities of daily living. For this reason, it is accepted that seizure control is only one feature of the clinical management of epilepsy, since cognitive, physical and psychological deterioration also affects quality of life. It is essential to have measurement tools that rapidly and accurately evaluate the complex aspects included in the concept of quality of life in persons with epilepsy. This study has aimed to validate the specific Health-Related Quality of Life (HRQoL) questionnaire for epileptic patients, QOLIE-10 (Quality of Life in Epilepsy Inventory-10), a reduced version having easier clinical application than the QOLIE-31 in a Spanish population. Naturalistic, prospective, national and multicenter study, in which 21 Spanish neurologists took part. Patients with partial or generalized epilepsy from 18 to 50 years, who were under monotherapy with lamotrigine or valproic acid and clinically stables, were included. Two visits were carried out, one basal visit and a 6, month follow-up visit. Sociodemographic, clinical (ti-me since diagnosis, previous treatment, current treatment and perceived adverse events) and social variables (QOLIE-31, QOLIE-10) were collected. A total of 107 patients were included. Mean age was 30.4 (deviation standard [DE]: 9.1) years and 61.7% were women. Mean time since epilepsy diagnosis was 8 (SD: 8.1) years. A total of 84.1% of the patients answered all the items correctly (feasibility). The Kaiser- Myer-Olkin measure was 0.822, with an associated pvalue<0.001 (content validity). QOLIE-10 scores did not show any relationship with the type of seizures (p>0.05), either globally or for its different domains (cross-sectional validity). The mean score went from 73.9 (SD: 15.7) to 75.5 (SD: 14.9) between the two visits, equivalent to an increase of HRQoL of 1.6 (SD: 7.6) points (p=0.37) (longitudinal validity). A Cronbach's alpha coefficient of 0.811 was obtained (internal consistency). Interclass correlation coefficients were higher than 0.7 (reliability). In the overall score the effect size obtained was of 0.10 (responsiveness to change). The Spanish version of the QOLIE-10 has been shown to be feasible, valid, reliable and responsive to changes. The QOLIE-10 is a useful tool to measure HRQoL in usual clinical practice.

[Nootropics and antioxidants in the complex therapy of symptomatic posttraumatic epilepsy].

PubMed

Savenkov, A A; Badalian, O L; Avakian, G N

2013-01-01

To study the possibility of application of nootropics and antioxidants in the complex antiepileptic therapy, we examined 75 patients with symptomatic focal posttraumatic epilepsy. A statistically significant reduction in the number of epileptic seizures, improvement of cognitive function and quality of life of the patients as well as a decrease in the severity of depression and epileptic changes in the EEG were identified. The potentiation of antiepileptic activity of basic drugs, normalization of brain's electrical activity and reduction in EEG epileptiform activity, in particular coherent indicators of slow-wave activity, were noted after treatment with the antioxidant mexidol. A trend towards the improvement of neuropsychological performance and quality of life was observed. There was a lack of seizure aggravation typical of many nootropic drugs. Thus, phenotropil and mexidol can be recommended for complex treatment of symptomatic posttraumatic epilepsy.

Development and evaluation of in situ gel of pregabalin

PubMed Central

Madan, Jyotsana R; Adokar, Bhushan R; Dua, Kamal

2015-01-01

Aim and Background: Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice. Materials and Methods: In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 32 full factorial design. Results: The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm2). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release. Conclusion: Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy. PMID:26682193

Interview: the National Institute of Neurological Diseases and Stroke/American Epilepsy Society benchmarks and research priorities for epilepsy research.

PubMed

Lowenstein, Daniel H

2011-10-01

Daniel H Lowenstein, MD, is the Robert B and Ellinor Aird Professor and Vice-Chairman of Neurology, Director of the Epilepsy Center, and Director of Physician-Scientist Education and Training at the University of California, San Francisco (UCSF). He received his BA in Mathematics from the University of Colorado and MD from Harvard Medical School. He completed his neurology residency training at UCSF. Dr Lowenstein is a clinician-scientist who has studied both basic science and clinical aspects of epilepsy. In recent years, he has been an organizer of a large-scale, international effort to study the complex genetics of epilepsy, known as the Epilepsy Phenome/Genome Project. He has been actively involved in advancing the cause of epilepsy at the national and international level. Dr Lowenstein served as President of the American Epilepsy Society from 2003 to 2004 and the National Institute of Neurological Diseases and Stroke (NINDS) Advisory Council from 2000 to 2004, and has overseen the development of the NINDS Epilepsy Research Benchmarks since their inception in 2000.

Multicenter transversal two-phase study to determine a national prevalence of epilepsy in Algeria.

PubMed

Moualek, Dalila; Pacha, Lamia Ali; Abrouk, Samira; Kediha, Mohamed Islam; Nouioua, Sonia; Aissa, Leila Ait; Bellatache, Mounia; Belarbi, Soreya; Slimani, Saddek; Khennouf, Houria; Fellahi, Lynda; El Amine Hamimed, Mohamed; Benali, Nadia; Chekkour, Mohamed Chahine; Maamoun, Ramdane; Dameche, Rachida; Assami, Salima; Tazir, Meriem

2012-01-01

The prevalence of epilepsy in Algeria is unknown. The aims of this multicenter transversal study were to determine the national prevalence and clinical characteristics of epilepsy in the Algerian population. This two-phase study was conducted in 5 circumscriptions and included 8,046 subjects aged over 2 months who attended the randomly selected public and private primary care clinics. In the phase 1 study, a questionnaire was submitted to the sample of patients. In the phase 2 study, all potentially epileptic people were examined by neurologists and a second questionnaire was submitted, eventually assessed by appropriate investigations. Sixty-seven patients were identified as having active epilepsy, giving a crude prevalence ratio of 8.32 per 1,000 (95% CI, 6.34-10.3) and an age-adjusted prevalence ratio of 8.9 per 1,000. The highest age-specific ratio was found in patients aged 10-19 years (16.92 per 1,000). Generalized seizures (68.7%) were more common than partial seizures (29.8%). Perinatal injuries were the major leading putative causes (11.9%). The prevalence of epilepsy of 8.32 determined in this study is relatively high. These results provide new epidemiological data and suggest that epilepsy remains an important public health issue to consider in Algeria. Copyright © 2012 S. Karger AG, Basel.

[The psychosocial challenges of epilepsy and the role of the clinical nurse specialist].

PubMed

Chartrand, Dominic

2015-01-01

Epilepsy in children is a complex disease with significant psychosocial consequences for the child and their family. The intervention of a multidisciplinary team enables the care to be adapted and provides support for the families. At Sainte-Justine Hospital in Montreal, Canada, the nurse clinician specialised in epilepsy plays a key role in this team. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

PubMed

Scharfman, Helen E; Kanner, Andres M; Friedman, Alon; Blümcke, Ingmar; Crocker, Candice E; Cendes, Fernando; Diaz-Arrastia, Ramon; Förstl, Hans; Fenton, André A; Grace, Anthony A; Palop, Jorge; Morrison, Jason; Nehlig, Astrid; Prasad, Asuri; Wilcox, Karen S; Jette, Nathalie; Pohlmann-Eden, Bernd

2018-01-01

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted. Copyright © 2017 Elsevier Inc. All rights reserved.

Nodding syndrome in Tanzania may not be associated with circulating anti-NMDA-and anti-VGKC receptor antibodies or decreased pyridoxal phosphate serum levels-a pilot study.

PubMed

Dietmann, Anelia; Wallner, Bernd; König, Rebekka; Friedrich, Katrin; Pfausler, Bettina; Deisenhammer, Florian; Griesmacher, Andrea; Seger, Christoph; Matuja, William; JilekAall, Louise; Winkler, Andrea S; Schmutzhard, Erich

2014-06-01

Nodding syndrome (NS) is a seemingly progressive epilepsy disorder of unknown underlying cause. We investigated association of pyridoxal-phosphate serum levels and occurrence of anti-neuronal antibodies against N-methyl-D-aspartate (NMDA) receptor and voltage gated potassium channel (VGKC) complex in NS patients. Sera of a Tanzanian cohort of epilepsy and NS patients and community controls were tested for the presence of anti-NMDA-receptor and anti-VGKC complex antibodies by indirect immunofluorescence assay. Furthermore pyridoxal-phosphate levels were measured. Auto-antibodies against NMDA receptor or VGKC (LG1 or Caspr2) complex were not detected in sera of patients suffering from NS (n=6), NS plus other seizure types (n=16), primary generalized epilepsy (n=1) and community controls without epilepsy (n=7). Median Pyridoxal-phosphate levels in patients with NS compared to patients with primary generalized seizures and community controls were not significantly different. However, these median pyridoxal-phosphate levels are significantly lower compared to the range considered normal in Europeans. In this pilot study NS was not associated with serum anti-NMDA receptor or anti-VGKC complex antibodies and no association to pyridoxal-phosphate serum levels was found.

Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy

PubMed Central

Tambucci, Renato; Basti, Claudia; Maresca, Maria; Coppola, Giangennaro; Verrotti, Alberto

2016-01-01

Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine – a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC). ESL inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the VGSC, thus selectively reducing the activity of rapidly firing (epileptic) neurons. ESL reduces VGSC availability through enhancement of slow inactivation. In Phase III studies, adjunctive therapy with ESL 800 or 1,200 mg/day leads to a significant decrease in the seizure frequency in adults with refractory partial onset epilepsy. Based on these results, ESL has been approved in Europe (by the European Medicines Agency) and in the United States (by the US Food and Drug Administration) as add-on therapy. Data on efficacy and safety have been confirmed by 1-year extension and real life observational studies. Recently, based on results from two randomized, double-blind, historical control Phase III trials, ESL received US Food and Drug Administration approval also as a monotherapy for patients with partial onset epilepsy. In the pediatric setting, encouraging results have been obtained suggesting its potential role in the management of epileptic children. Overall ESL was generally well tolerated. The most common adverse events were dizziness, somnolence, headache, nausea, diplopia, and vomiting. Adverse events can be minimized by appropriate titration. In conclusion, ESL seems to overcome some drawbacks of the previous antiepileptic drugs, suggesting a major role of ESL in the management of focal onset epilepsy for both new onset and refractory cases, either as monotherapy or as adjunctive treatment. PMID:27307737

Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy.

PubMed

Tambucci, Renato; Basti, Claudia; Maresca, Maria; Coppola, Giangennaro; Verrotti, Alberto

2016-01-01

Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine - a dibenzazepine nucleus with the 5-carboxamide substituent, but is structurally different at the 10,11-position. ESL is a pro-drug metabolized to its major active metabolite eslicarbazepine. Despite the fact that the exact mechanism of action has not been fully elucidated, it is thought to involve inhibition of voltage-gated sodium channels (VGSC). ESL inhibits sodium currents in a voltage-dependent way by an interaction predominantly with the inactivated state of the VGSC, thus selectively reducing the activity of rapidly firing (epileptic) neurons. ESL reduces VGSC availability through enhancement of slow inactivation. In Phase III studies, adjunctive therapy with ESL 800 or 1,200 mg/day leads to a significant decrease in the seizure frequency in adults with refractory partial onset epilepsy. Based on these results, ESL has been approved in Europe (by the European Medicines Agency) and in the United States (by the US Food and Drug Administration) as add-on therapy. Data on efficacy and safety have been confirmed by 1-year extension and real life observational studies. Recently, based on results from two randomized, double-blind, historical control Phase III trials, ESL received US Food and Drug Administration approval also as a monotherapy for patients with partial onset epilepsy. In the pediatric setting, encouraging results have been obtained suggesting its potential role in the management of epileptic children. Overall ESL was generally well tolerated. The most common adverse events were dizziness, somnolence, headache, nausea, diplopia, and vomiting. Adverse events can be minimized by appropriate titration. In conclusion, ESL seems to overcome some drawbacks of the previous antiepileptic drugs, suggesting a major role of ESL in the management of focal onset epilepsy for both new onset and refractory cases, either as monotherapy or as adjunctive treatment.

The ventrolateral medulla and medullary raphe in sudden unexpected death in epilepsy.

PubMed

Patodia, Smriti; Somani, Alyma; O'Hare, Megan; Venkateswaran, Ranjana; Liu, Joan; Michalak, Zuzanna; Ellis, Matthew; Scheffer, Ingrid E; Diehl, Beate; Sisodiya, Sanjay M; Thom, Maria

2018-06-01

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in patients with epilepsy. One hypothesis proposes that sudden death is mediated by post-ictal central respiratory depression, which could relate to underlying pathology in key respiratory nuclei and/or their neuromodulators. Our aim was to investigate neuronal populations in the ventrolateral medulla (which includes the putative human pre-Bötzinger complex) and the medullary raphe. Forty brainstems were studied comprising four groups: 14 SUDEP, six epilepsy controls, seven Dravet syndrome cases and 13 non-epilepsy controls. Serial sections through the medulla (from obex 1 to 10 mm) were stained for Nissl, somatostatin, neurokinin 1 receptor (for pre-Bötzinger complex neurons) and galanin, tryptophan hydroxylase and serotonin transporter (neuromodulatory systems). Using stereology total neuronal number and densities, with respect to obex level, were measured. Whole slide scanning image analysis was used to quantify immunolabelling indices as well as co-localization between markers. Significant findings included reduction in somatostatin neurons and neurokinin 1 receptor labelling in the ventrolateral medulla in sudden death in epilepsy compared to controls (P < 0.05). Galanin and tryptophan hydroxylase labelling was also reduced in sudden death cases and more significantly in the ventrolateral medulla region than the raphe (P < 0.005 and P < 0.05). With serotonin transporter, reduction in labelling in cases of sudden death in epilepsy was noted only in the raphe (P ≤ 0.01); however, co-localization with tryptophan hydroxylase was significantly reduced in the ventrolateral medulla. Epilepsy controls and cases with Dravet syndrome showed less significant alterations with differences from non-epilepsy controls noted only for somatostatin in the ventrolateral medulla (P < 0.05). Variations in labelling with respect to obex level were noted of potential relevance to the rostro-caudal organization of respiratory nuclear groups, including tryptophan hydroxylase, where the greatest statistical difference noted between all epilepsy cases and controls was at obex 9-10 mm (P = 0.034), the putative level of the pre-Bötzinger complex. Furthermore, there was evidence for variation with duration of epilepsy for somatostatin and neurokinin 1 receptor. Our findings suggest alteration to neuronal populations in the medulla in SUDEP with evidence for greater reduction in neuromodulatory neuropeptidergic and mono-aminergic systems, including for galanin, and serotonin. Other nuclei need to be investigated to evaluate if this is part of more widespread brainstem pathology. Our findings could be a result of previous seizures and may represent a pathological risk factor for SUDEP through impaired respiratory homeostasis during a seizure.

Genetic variations and associated pathophysiology in the management of epilepsy.

PubMed

Mulley, John C; Dibbens, Leanne M

2011-01-01

The genomic era has enabled the application of molecular tools to the solution of many of the genetic epilepsies, with and without comorbidities. Massively parallel sequencing has recently reinvigorated gene discovery for the monogenic epilepsies. Recurrent and novel copy number variants have given much-needed impetus to the advancement of our understanding of epilepsies with complex inheritance. Superimposed upon that is the phenotypic blurring by presumed genetic modifiers scattering the effects of the primary mutation. The genotype-first approach has uncovered associated syndrome constellations, of which epilepsy is only one of the syndromes. As the molecular genetic basis for the epilepsies unravels, it will increasingly influence the classification and diagnosis of the epilepsies. The ultimate goal of the molecular revolution has to be the design of treatment protocols based on genetic profiles, and cracking the 30% of epilepsies refractory to current medications, but that still lies well into the future. The current focus is on the scientific basis for epilepsy. Understanding its genetic causes and biophysical mechanisms is where we are currently positioned: prizing the causes of epilepsy "out of the shadows" and exposing its underlying mechanisms beyond even the ion-channels.

Frontal lobe epilepsy.

PubMed

Kellinghaus, Christoph; Lüders, Hans O

2004-12-01

Frontal lobe epilepsy accounts for only 10-20% of the patients in surgical series, but the incidence in non-surgical patient cohorts seems to be much higher. The typical clinical presentation of the seizures includes contralateral clonic movements, uni- or bilateral tonic motor activity as well as complex automatism. The yield of surface EEG may be limited due to the difficulty in detection of mesial or basal foci, and the patient may be misdiagnosed as having non-epileptic events. In addition, in patients with mesial frontal foci the epileptiform discharges may be mislateralized ("paradoxical lateralization"). Therefore, epilepsy surgery has been commonly considered as less promising in patients with frontal lobe epilepsy. However, the advent of sophisticated neuroimaging techniques, particularly MRI with epilepsy-specific sequences, has made it possible to delineate the epileptogenic lesion and detect a specific etiology, in an increasing number of patients. Thus, the success rate of epilepsy surgery in frontal lobe epilepsy is currently comparable to temporal lobe epilepsy, if the candidates are carefully selected. Patients with frontal lobe epilepsy who do not respond to anticonvulsive medication, and who are not eligible for epilepsy surgery may benefit from alternative approaches such as electrical brain stimulation.

Effects of levetiracetam monotherapy on sperm parameters and sex hormones: Data from newly diagnosed patients with epilepsy.

PubMed

Ceylan, Mustafa; Yalcin, Ahmet; Bayraktutan, Omer Faruk; Karabulut, Ibrahim; Sonkaya, Ali Rıza

2016-10-01

Epilepsy has an impact on the reproductive system. Males with epilepsy have lower fertility rates, hypo-sexuality and reduced potency compared with the general population. Anti-epileptic drugs and epilepsy itself are thought to be responsible for this reduced fertility. LEV is a second-generation anti-epileptic agent with low incidences of both adverse effects and drug-drug interactions. In this study, we have investigated the effects of LEV treatment on sex hormones and sperm parameters in newly diagnosed epilepsy patients. We recruited 26 males with newly diagnosed epilepsy and introduced LEV monotherapy. Patients were divided into two groups depending on whether they had partial or generalized seizures. We acquired the results of pre- and post-treatment sperm analyses and serum sex hormone levels. We also recorded the maximum dose, daily dose and treatment duration for each individual. Pre- and post-treatment comparisons and correlations between both sperm and sex hormone parameters and both treatment duration and dose were determined. Pre- and post-treatment sex hormone levels were not significantly different. The total sperm count, percentage of normal morphology and functional sperm count tested after treatment were significantly lower in both groups compared with pre-treatment values (p<0.05). There was a moderate correlation between daily dose and reduction in functional sperm count (r: 0.41, p: 0.034). Our findings confirm that LEV treatment of newly diagnosed epilepsy patients decreases sperm parameters without altering sex hormone levels. Our results may guide the choice of anti-epileptic drug treatment among men with epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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.

Comparison of impact on seizure frequency and epileptiform discharges of children with epilepsy from topiramate and phenobarbital.

PubMed

Wang, Y-Y; Wang, M-G; Yao, D; Huang, X-X; Zhang, T; Deng, X-Q

2016-03-01

To study the impact on seizure frequency and epileptiform discharges of children with epilepsy from topiramate (TPM) and phenobarbital (PB). Two hundred cases children with epilepsy from August 2010 to August 2013 in our hospital were sampled and randomly divided into two groups. The observation group was treated with TPM while the control group with PB, and then comparing seizure frequency, efficiency, and adverse reactions of two groups. The reduced number of partial seizures, generalized seizures, and total seizures in the observation group were significantly higher than those in the control group, and the rate of cure, markedly effective and total efficiency in observation group were significantly higher than those in the control group. However, the adverse reactions in observation group were significantly lower than those in the control group. Thus, differences were statistically significant (p<0.05). Compared with PB, TPM showed a better effect on epilepsy treatment with less adverse reactions which were worthy of clinical recommendation.

Epilepsy coexisting with depression.

PubMed

Błaszczyk, Barbara; Czuczwar, Stanisław J

2016-10-01

Depression episodes in epilepsy is the most common commorbidity, affecting between 11% and 62% of patients with epilepsy. Although researchers have documented a strong association between epilepsy and psychiatric comorbidities, the nature of this relationship is poorly understood. The manifestation of depression in epilepsy is a complex issue having many interacting neurobiological and psychosocial determinants, including clinical features of epilepsy (seizure frequency, type, foci, or lateralization of foci) and neurochemical or iatrogenic mechanisms. Other risk factors are a family history of psychiatric illness, particularly depression, a lack of control over the seizures and iatrogenic causes (pharmacologic and surgical). In addition, treatment with antiepileptic drugs (AEDs) as well as social coping and adaptation skills have also been recognised as risk factors of depression associated with epilepsy. Epilepsy may foster the development of depression through being exposed to chronic stress. The uncertainty and unpredictability of seizures may instigate sadness, loneliness, despair, low self-esteem, and self-reproach in patients with epilepsy and lead to social isolation, stigmatization, or disability. Often, depression is viewed as a reaction to epilepsy's stigma and the associated poor quality of life. Moreover, patients with epilepsy display a 4-5 higher rate of depression and suicide compared with healthy population. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome.

PubMed

Danti, Federica Rachele; Galosi, Serena; Romani, Marta; Montomoli, Martino; Carss, Keren J; Raymond, F Lucy; Parrini, Elena; Bianchini, Claudia; McShane, Tony; Dale, Russell C; Mohammad, Shekeeb S; Shah, Ubaid; Mahant, Neil; Ng, Joanne; McTague, Amy; Samanta, Rajib; Vadlamani, Gayatri; Valente, Enza Maria; Leuzzi, Vincenzo; Kurian, Manju A; Guerrini, Renzo

2017-04-01

To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1 -related disease. We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia.

Understanding the Patient Perspective of Seizure Severity in Epilepsy: Development of a Conceptual Model.

PubMed

Borghs, Simon; Tomaszewski, Erin L; Halling, Katarina; de la Loge, Christine

2016-10-01

For patients with uncontrolled epilepsy, the severity and postictal sequelae of seizures might be more impactful than their frequency. Seizure severity is often assessed using patient-reported outcome (PRO) instruments; however, evidence of content validity for existing instruments is lacking. Our aim was to understand the real-life experiences of patients with uncontrolled epilepsy. A preliminary conceptual model was developed. The model was refined through (1) a targeted literature review of qualitative research on seizure severity; (2) interviews with four clinical epilepsy experts to evaluate identified concepts; and (3) qualitative interviews with patients with uncontrolled epilepsy, gathering descriptions of symptoms and impacts of epilepsy, focusing on how patients experience and describe "seizure severity." Findings were summarized in a final conceptual model of seizure severity in epilepsy. Twenty-five patients (12 who experienced primary generalized tonic-clonic seizures and 13 who experienced partial-onset seizures) expressed 42 different symptoms and 26 different impacts related to seizures. The final conceptual model contained a wide range of concepts related to seizure frequency, symptoms, and duration. Our model identified several new concepts that characterize the patient experience of seizure severity. A seizure severity PRO instrument should cover a wide range of seizure symptoms alongside frequency and duration of seizures. This qualitative work reinforces the notion that measuring seizure frequency is insufficient and that seizure severity is important in defining the patient's experience of epilepsy. This model could be used to assess the content validity of existing PRO instruments, or could support the development of a new one.

National and State Estimates of the Numbers of Adults and Children with Active Epilepsy - United States, 2015.

PubMed

Zack, Matthew M; Kobau, Rosemarie

2017-08-11

Epilepsy, a brain disorder leading to recurring seizures, has garnered increased public health focus because persons with epilepsy experience pronounced and persistent health and socioeconomic disparities despite treatment advances, public awareness programs, and expanded rights for persons with disabilities (1,2). For almost all states, epilepsy prevalence estimates do not exist. CDC used national data sources including the 2015 National Health Interview Survey (NHIS) for adults (aged ≥18 years), the 2011-2012 National Survey of Children's Health (NSCH), and the 2015 Current Population Survey data, describing 2014 income levels, to estimate prevalent cases of active epilepsy, overall and by state, to provide information for state public health planning. In 2015, 1.2% of the U.S. population (3.4 million persons: 3 million adults and 470,000 children) reported active epilepsy (self-reported doctor-diagnosed epilepsy and under treatment or with recent seizures within 12 months of interview) or current epilepsy (parent-reported doctor-diagnosed epilepsy and current epilepsy). Estimated numbers of persons with active epilepsy, after accounting for income and age differences by state, ranged from 5,900 in Wyoming to 427,700 in California. NHIS data from 2010-2015 indicate increases in the number of persons with active epilepsy, probably because of population growth. This study provides updated national and modeled state-specific numbers of active epilepsy cases. Public health practitioners, health care providers, policy makers, epilepsy researchers, and other epilepsy stakeholders, including family members and people with epilepsy, can use these findings to ensure that evidence-based programs meet the complex needs of adults and children with epilepsy and reduce the disparities resulting from it.

The Role of 5-Hydroxymethylcytosine in Gene Dysregulation of Epileptogenic Tubers in Tuberous Sclerosis Complex Patients

DTIC Science & Technology

2015-10-01

epilepsy risk genes in epileptogenic TSC tubers. We are using semiconductor sequencing to characterize 5hmC in DNA of epileptogenic and non...epileptogenic brain tubers that were surgically resected from TSC patients to treat intractable epilepsy . During the reporting period we successfully... epilepsy risk genes. We will then measure gene expression levels for these genes. The outcomes of this research are expected to expand our understanding

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

‘Forced normalisation’ in the neurosurgical era

PubMed Central

Shahani, Lokesh

2012-01-01

The correlation between epilepsy and behavioural disorders is well known. Forced normalisation is a phenomenon where there is worsening of the patient's behavioural disorder when a better seizure control has been obtained. A complication of anti-epileptic treatment worsening the behavioural disorder is sometimes the proposed mechanism. The author presents the report of a young man with temporal lobe epilepsy and poor seizure control in the past 12 years. The patient had comorbid impulse control disorder previously well controlled with medications. MRI demonstrated left mesial temporal sclerosis and intracranial EEG recording located seizure foci in the left medial temporal lobe. The patient underwent left temporal lobectomy for seizure control with partial success. However, after operation, the patient's impulse control disorder worsened and he was involved in physical altercations leading to incarceration. This illustrates a case where partial seizure control was obtained with a surgical procedure, but resulted in worsening of the patient's behavioural disorder. PMID:22684833

Status epilepticus developing during lacosamide monotherapy

PubMed Central

Papacostas, Savvas S

2015-01-01

Two cases with partial onset epilepsy who developed status epilepticus (SE) on lacosamide (LCM) monotherapy are reported. LCM is an effective adjunctive antiepileptic drug (AED) for partial-onset epilepsy and as infusion in SE. It has also shown efficacy in monotherapy. The reported cases achieved control of seizures with adjunctive LCM treatment and were afterwards converted to monotherapy. Both patients subsequently developed SE while on LCM monotherapy. They were on monotherapy for at least 2 months after withdrawal of concomitant AEDs precluding the possibility of withdrawal-induced SE. Pharmacovigilance is indicated when LCM is administered in monotherapy in order to assess its proper therapeutic potential and its putative limitations especially in cases where it may prove ineffective. Moreover, vigilance is necessary whenever any concomitant antiepileptic is tapered regardless of the substances used. Higher doses may be needed when an AED is used in monotherapy. PMID:25628098

Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex.

PubMed

Jeong, Anna; Wong, Michael

2016-09-01

Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p < 0.001), shagreen patches (OR 1.7, CI 1.0-2.7, p = 0.04), and facial angiofibromas (OR 1.7, CI 1.1-2.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease prognostication and assist in the identification of individuals who may receive maximal benefit from potentially novel, targeted, preventative therapies. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Persons with Epilepsy: Between Social Inclusion and Marginalisation

PubMed Central

Mlinar, Simona; Petek, Davorina; Cotič, Živa; Mencin Čeplak, Metka; Zaletel, Marjan

2016-01-01

Background. Epilepsy is a chronic neurological disorder that can lead to complex psychosocial consequences. Epilepsy can change the social status of persons with epilepsy (PWE) and has an effect on their social inclusion as well as their perception of social inclusion. This study aims to explore subjective experiences with social inclusion of PWE in Slovenia. Methods. This study takes a qualitative approach. Eleven semistructured interviews were conducted with eleven participants. Interviews were analysed using thematic analysis. Results. Epilepsy has physical, emotional, and social consequences. Physical consequences of epilepsy are mainly tiredness and exhaustion following an epileptic episode, frequently accompanied by headaches. Emotional consequences are different forms of fear. The main social consequence identified is a negative effect on PWE's social network, which leads to (self-)isolation and social distrust. Conclusion. PWE experience of social inclusion depends on various psychosocial factors and differs from person to person. The consequences of epilepsy are shown in PWE social contacts and their sense of social inclusion and autonomy. PMID:27212802

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.

Persons with Epilepsy: Between Social Inclusion and Marginalisation.

PubMed

Mlinar, Simona; Petek, Davorina; Cotič, Živa; Mencin Čeplak, Metka; Zaletel, Marjan

2016-01-01

Epilepsy is a chronic neurological disorder that can lead to complex psychosocial consequences. Epilepsy can change the social status of persons with epilepsy (PWE) and has an effect on their social inclusion as well as their perception of social inclusion. This study aims to explore subjective experiences with social inclusion of PWE in Slovenia. This study takes a qualitative approach. Eleven semistructured interviews were conducted with eleven participants. Interviews were analysed using thematic analysis. Epilepsy has physical, emotional, and social consequences. Physical consequences of epilepsy are mainly tiredness and exhaustion following an epileptic episode, frequently accompanied by headaches. Emotional consequences are different forms of fear. The main social consequence identified is a negative effect on PWE's social network, which leads to (self-)isolation and social distrust. PWE experience of social inclusion depends on various psychosocial factors and differs from person to person. The consequences of epilepsy are shown in PWE social contacts and their sense of social inclusion and autonomy.

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

Sleep disorders in adults with epilepsy: past, present, and future directions.

PubMed

Grigg-Damberger, Madeleine M; Ralls, Frank

2014-11-01

To summarize recent studies on the complex relationships between sleep disorders, sleep, and epilepsy. Insomnia in adults with epilepsy (AWE) warrants consideration of depression, anxiety, and suicidal ideation. Daytime sleepiness in AWE is more often due to undiagnosed sleep disorders. Sleep deprivation is an important provoker of seizures in juvenile myoclonic epilepsy. Abnormalities in frontal lobe executive function with difficulties making advantageous decisions may explain failure of juvenile myoclonic epilepsy patients to adhere to treatment recommendations and regulate their sleep habits. Sleep architecture in AWE is more likely to be abnormal if seizures are poorly controlled or occur during sleep. Obstructive sleep apnea is much more common in AWE who are man, older, heavier, or whose seizures are poorly controlled. Chronobiology and chronopharmacology of epilepsy is an emerging field worthy of future research and clinical applications. Identifying and treating unrecognized sleep disorders and understanding the impact of circadian rhythms on epilepsy can improve quality of life and seizure control in AWE.

Impact of sleep duration on seizure frequency in adults with epilepsy: a sleep diary study.

PubMed

Cobabe, Maurine M; Sessler, Daniel I; Nowacki, Amy S; O'Rourke, Colin; Andrews, Noah; Foldvary-Schaefer, Nancy

2015-02-01

Prolonged sleep deprivation activates epileptiform EEG abnormalities and seizures in people with epilepsy. Few studies have addressed the effect of chronic partial sleep deprivation on seizure occurrence in populations with epilepsy. We tested the primary hypothesis that partial sleep deprivation over 24- and 72-hour periods increases seizure occurrence in adults with epilepsy. Forty-four subjects completed a series of self-reported instruments, as well as 1-month sleep and seizure diaries, to characterize their sleep and quality of life. Diaries were used to determine the relationship between seizure occurrence and total sleep time 24 and 72h before seizure occurrence using random effects models and a logistic regression model fit by generalized estimating equations. A total of 237 seizures were recorded during 1295 diary days, representing 5.5±7.0 (mean±SD) seizures per month. Random effects models for 24- and 72-hour total sleep times showed no clinically or statistically significant differences in the total sleep time between preseizure periods and seizure-free periods. The average 24-hour total sleep time during preseizure 24-hour periods was 8min shorter than that during seizure-free periods (p=0.51). The average 72-hour total sleep time during preseizure periods was 20min longer than that during seizure-free periods (p=0.86). The presence of triggers was a significant predictor of seizure occurrence, with stress/anxiety noted most often as a trigger. Mean total sleep time was 9h, and subjects took an average of 12±10 naps per month, having a mean duration of 1.9±1.2h. Daytime sleepiness, fatigue, and insomnia symptoms were commonly reported. Small degrees of sleep loss were not associated with seizure occurrence in our sample of adults with epilepsy. Our results also include valuable observations of the altered sleep times and frequent napping habits of adults with refractory epilepsy and the potential contribution of these habits to quality of life and seizure control. Copyright © 2014 Elsevier Inc. All rights reserved.

Electrographic waveform structure predicts laminar focus location in a model of temporal lobe seizures in vitro.

PubMed

Adams, Christopher; Adams, Natalie E; Traub, Roger D; Whittington, Miles A

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is 'victim' or 'perpetrator': The structure is ideally placed to 'broadcast' epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin - a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.

Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

PubMed Central

Adams, Christopher; Adams, Natalie E.; Traub, Roger D.; Whittington, Miles A.

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role. PMID:25799020

Sex and Hormonal influences on Seizures and Epilepsy

PubMed Central

Velíšková, Jana; DeSantis, Kara A.

2012-01-01

Epilepsy is the third most common chronic neurological disorder. Clinical and experimental evidence supports the role of sex and influence of sex hormones on seizures and epilepsy as well as alterations of the endocrine system and levels of sex hormones by epileptiform activity. Conversely, seizures are sensitive to changes in sex hormone levels, which in turn may affect the seizure-induced neuronal damage. The effects of reproductive hormones on neuronal excitability and seizure-induced damage are complex to contradictory and depend on different mechanisms, which have to be accounted for in data interpretation. Both estradiol and progesterone/allopregnanolone may have beneficial effects for patients with epilepsy. Individualized hormonal therapy should be considered as adjunctive treatment in patients with epilepsy to improve seizure control as well as quality of life. PMID:22504305

Recent advances in drug therapy for epilepsy.

PubMed Central

Bruni, J.

1979-01-01

Recent advances in drug therapy for epilepsy have contributed to the reduction in the proportion of persons whose epilepsy is uncontrolled. New knowledge of the pharmacokinetics of phenytoin has led to a better understanding of the drug's bioavailability and uses. Carbamazepine has recently been introduced for the treatment of generalized tonic-clonic and partial seizures. Clonazepam has been found of particular benefit in the treatment of absence and myoclonic seizures. Valproic acid is a promising antiepileptic drug with broad-spectrum activity, and is particularly useful in the treatment of absence and myoclonic seizures, although further clinical experience is required before it can supplant ethosuximide as the preferred drug for the treatment of absence seizures. Monitoring of the plasma concentration of antiepileptic drugs has added greatly to the achievement of optimal drug therapy and the prevention of toxic effects. PMID:371777

Describing the genetic architecture of epilepsy through heritability analysis.

PubMed

Speed, Doug; O'Brien, Terence J; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G; Balding, David J; Johnson, Michael R

2014-10-01

Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital.

PubMed

Habib, Mansur; Khan, Sharif Uddin; Hoque, Azhahul; Mondal, Badrul Alam; Hasan, A T M Hasibul; Chowdhury, Rajib Nayan; Haque, Badrul; Rahman, Kazi Mohibur; Chowdhury, Ahmed Hossain; Ghose, Swapon Kumar; Mohammad, Quazi Deen

2013-11-18

Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the combination regimens had a treatment retention rate of 100%. The effectiveness of AED in terms of reduction of seizure frequency was highest for PHT (100%) and PHB (98%) followed by CBZ (96%) and VPA (95%). PHB and PHT were the cheapest of all AEDs (42 I$ and 56 I$/ year respectively). The costs of VPA and CBZ were two times and LTG and TOP were six to eight times higher. Adverse drug reaction (ADR) were observed among 140 (24.5%) of those with monotherapy. PHT (64%) was the most common drug to cause ADR, CBZ was at the bottom of the list to cause adverse effect (11.6%). VPA and PHB caused weight gain commonly. Adjustment of drug dose or withdrawal due to ADRs was necessary in 39% with PHT and 26% with PHB. Though PHT and PHB are cheapest and efficacious among all, CBZ and VPA are less costly, effective and well tolerated drug for seizure control in context of Bangladesh.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2015-12-03

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Outcome of childhood-onset epilepsy from adolescence to adulthood: Transition issues.

PubMed

Nabbout, R; Andrade, D M; Bahi-Buisson, N; Cross, H; Desquerre, I; Dulac, O; Granata, T; Hirsch, E; Navarro, V; Ouss, L; Pearl, P L; Schmidt, D; Thiele, E; Camfield, P R; Camfield, C S

2017-04-01

This is the second of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper addresses the outcome for some particularly challenging childhood-onset epileptic disorders with the goal of recommending the best approach to transition. We have grouped these disorders in five categories with a few examples for each. The first group includes disorders presenting in childhood that may have late- or adult-onset epilepsy (metabolic and mitochondrial disorders). The second group includes disorders with changing problems in adulthood (tuberous sclerosis complex, Rett syndrome, Dravet syndrome, and autism). A third group includes epilepsies that change with age (Childhood Absence Epilepsy, Juvenile Myoclonic Epilepsy, West Syndrome, and Lennox-Gastaut syndrome). A fourth group consists of epilepsies that vary in symptoms and severity depending on the age of onset (autoimmune encephalitis, Rasmussen's syndrome). A fifth group has epilepsy from structural causes that are less likely to evolve in adulthood. Finally we have included a discussion about the risk of later adulthood cerebrovascular disease and dementia following childhood-onset epilepsy. A detailed knowledge of each of these disorders should assist the process of transition to be certain that attention is paid to the most important age-related symptoms and concerns. Copyright © 2016 Elsevier Inc. All rights reserved.

Wireless system for long-term EEG monitoring of absence epilepsy

NASA Astrophysics Data System (ADS)

Whitchurch, Ashwin K.; Ashok, B. H.; Kumaar, R. V.; Saurkesi, K.; Varadan, Vijay K.

2002-11-01

Absence epilepsy is a form of epilepsy common mostly in children. The most common manifestations of Absence epilepsy are staring and transient loss of responsiveness. Also, subtle motor activities may occur. Due to the subtle nature of these symptoms, episodes of absence epilepsy may often go unrecognized for long periods of time or be mistakenly attributed to attention deficit disorder or daydreaming. Spells of absence epilepsy may last about 10 seconds and occur hundreds of times each day. Patients have no recollections of the events that occurred during those seizures and will resume normal activity without any postictal symptoms. The EEG during such episodes of Absence epilepsy shows intermittent activity of 3 Hz generalized spike and wave complexes. As EEG is the only way of detecting such symptoms, it is required to monitor the EEG of the patient for a long time and thus remain only in bed. So, effectively the EEG is being monitored only when the patient is stationary. The wireless monitoring sys tem described in this paper aims at eliminating this constraint and enables the physicial to monitor the EEG when the patient resumes his normal activities. This approach could even help the doctor identify possible triggers of absence epilepsy.

Recurrent spontaneous motor seizures after repeated low-dose systemic treatment with kainate: assessment of a rat model of temporal lobe epilepsy.

PubMed

Hellier, J L; Patrylo, P R; Buckmaster, P S; Dudek, F E

1998-06-01

Human temporal lobe epilepsy is associated with complex partial seizures that can produce secondarily generalized seizures and motor convulsions. In some patients with temporal lobe epilepsy, the seizures and convulsions occur following a latent period after an initial injury and may progressively increase in frequency for much of the patient's life. Available animal models of temporal lobe epilepsy are produced by acute treatments that often have high mortality rates and/or are associated with a low proportion of animals developing spontaneous chronic motor seizures. In this study, rats were given multiple low-dose intraperitoneal (i.p.) injections of kainate in order to minimize the mortality rate usually associated with single high-dose injections. We tested the hypothesis that these kainate-treated rats consistently develop a chronic epileptic state (i.e. long-term occurrence of spontaneous, generalized seizures and motor convulsions) following a latent period after the initial treatment. Kainate (5 mg/kg per h, i.p.) was administered to rats every hour for several hours so that class III-V seizures were elicited for > or = 3 h, while control rats were treated similarly with saline. This treatment protocol had a relatively low mortality rate (15%). After acute treatment, rats were observed for the occurrence of motor seizures for 6-8 h/week. Nearly all of the kainate-treated rats (97%) had two or more spontaneous motor seizures months after treatment. With this observation protocol, the average latency for the first spontaneous motor seizure was 77+/-38 (+/-S.D.) days after treatment. Although variability was observed between rats, seizure frequency initially increased with time after treatment, and nearly all of the kainate-treated rats (91%) had spontaneous motor seizures until the time of euthanasia (i.e. 5-22 months after treatment). Therefore, multiple low-dose injections of kainate, which cause recurrent motor seizures for > or = 3 h, lead to the development of a chronic epileptic state that is characterized by (i) a latent period before the onset of chronic motor seizures, and (ii) a high but variable seizure frequency that initially increases with time after the first chronic seizure. This modification of the kainate-treatment protocol is efficient and relatively simple, and the properties of the chronic epileptic state appear similar to severe human temporal lobe epilepsy. Furthermore, the observation that seizure frequency initially increased as a function of time after kainate treatment supports the hypothesis that temporal lobe epilepsy can be a progressive syndrome.

Prevalence and incidence of epilepsy in the Nordic countries.

PubMed

Syvertsen, Marte; Koht, Jeanette; Nakken, Karl O

2015-10-06

Updated knowledge on the prevalence of epilepsy is valuable for planning of health services to this large and complex patient group. Comprehensive epidemiological research on epilepsy has been undertaken, but because of variations in methodology, the results are difficult to compare. The objective of this article is to present evidence-based estimates of the prevalence and incidence of epilepsy in the Nordic countries. The article is based on a search in PubMed with the search terms epilepsy and epidemiology, combined with each of the Nordic countries separately. Altogether 38 original articles reported incidence and/or prevalence rates of epilepsy in a Nordic country. Four studies had investigated the prevalence of active epilepsy in all age groups, with results ranging from 3.4 to 7.6 per 1,000 inhabitants. Only two studies had investigated the incidence of epilepsy in a prospective material that included all age groups. The reported incidence amounted to 33 and 34 per 100,000 person-years respectively. A prospective study that only included adults reported an incidence of 56 per 100,000 person-years. We estimate that approximately 0.6% of the population of the Nordic countries have active epilepsy, i.e. approximately 30,000 persons in Norway. Epilepsy is thus one of the most common neurological disorders. The incidence data are more uncertain, but we may reasonably assume that 30-60 new cases occur per 100,000 person-years.

Pharmacotherapy of focal epilepsy in children: a systematic review of approved agents.

PubMed

Arya, Ravindra; Glauser, Tracy A

2013-04-01

Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation. This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children. Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors' files. Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria. Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data. Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partial-onset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures. This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug's efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.

Convulsive status epilepticus and health-related quality of life in children with epilepsy.

PubMed

Ferro, Mark A; Chin, Richard F M; Camfield, Carol S; Wiebe, Samuel; Levin, Simon D; Speechley, Kathy N

2014-08-19

The objective of this study was to examine the association between convulsive status epilepticus (CSE) and health-related quality of life (HRQL) during a 24-month follow-up in a multisite incident cohort of children with epilepsy. Data were collected in the Health-Related Quality of Life Study in Children with Epilepsy Study from 374 families of children with newly diagnosed epilepsy. The Quality of Life in Childhood Epilepsy (QOLCE) Questionnaire was used to evaluate parent-reported child HRQL. Hierarchical linear regression was used to examine the relationship between CSE and HRQL at 24 months postepilepsy. A total of 359 families completed the 24-month assessment. Twenty-two children (6.1%) had experienced CSE during the follow-up. Children with and without CSE were similar, except a larger proportion of children with CSE had partial seizures (p < 0.001). Controlling for clinical, demographic, and family characteristics, CSE was significantly associated with poorer HRQL (β = -4.65, p = 0.031). The final model explained 47% of the variance in QOLCE scores. The findings suggested that not only do children with CSE have significantly poorer HRQL compared with their non-CSE counterparts, but that this factor is independent of the effects of demographic and clinical features known to affect HRQL. © 2014 American Academy of Neurology.

Convulsive status epilepticus and health-related quality of life in children with epilepsy

PubMed Central

Chin, Richard F.M.; Camfield, Carol S.; Wiebe, Samuel; Levin, Simon D.; Speechley, Kathy N.

2014-01-01

Objectives: The objective of this study was to examine the association between convulsive status epilepticus (CSE) and health-related quality of life (HRQL) during a 24-month follow-up in a multisite incident cohort of children with epilepsy. Methods: Data were collected in the Health-Related Quality of Life Study in Children with Epilepsy Study from 374 families of children with newly diagnosed epilepsy. The Quality of Life in Childhood Epilepsy (QOLCE) Questionnaire was used to evaluate parent-reported child HRQL. Hierarchical linear regression was used to examine the relationship between CSE and HRQL at 24 months postepilepsy. A total of 359 families completed the 24-month assessment. Results: Twenty-two children (6.1%) had experienced CSE during the follow-up. Children with and without CSE were similar, except a larger proportion of children with CSE had partial seizures (p < 0.001). Controlling for clinical, demographic, and family characteristics, CSE was significantly associated with poorer HRQL (β = −4.65, p = 0.031). The final model explained 47% of the variance in QOLCE scores. Conclusions: The findings suggested that not only do children with CSE have significantly poorer HRQL compared with their non-CSE counterparts, but that this factor is independent of the effects of demographic and clinical features known to affect HRQL. PMID:25037204

Correlates of posttraumatic epilepsy 35 years following combat brain injury(CME)

PubMed Central

Raymont, V.; Salazar, A.M.; Lipsky, R.; Goldman, D.; Tasick, G.; Grafman, J.

2010-01-01

Background: The Vietnam Head Injury Study (VHIS) is a prospective, longitudinal follow-up of 1,221 Vietnam War veterans with mostly penetrating head injuries (PHIs). The high prevalence (45%–53%) of posttraumatic epilepsy (PTE) in this unique cohort makes it valuable for study. Methods: A standardized multidisciplinary neurologic, cognitive, behavioral, and brain imaging evaluation was conducted on 199 VHIS veterans plus uninjured controls, some 30 to 35 years after injury, as part of phase 3 of this study. Results: The prevalence of seizures (87 patients, 43.7%) was similar to that found during phase 2 evaluations 20 years earlier, but 11 of 87 (12.6%) reported very late onset of PTE after phase 2 (more than 14 years after injury). Those patients were not different from patients with earlier-onset PTE in any of the measures studied. Within the phase 3 cohort, the most common seizure type last experienced was complex partial seizures (31.0%), with increasing frequency after injury. Of subjects with PTE, 88% were receiving anticonvulsants. Left parietal lobe lesions and retained ferric metal fragments were associated with PTE in a logistic regression model. Total brain volume loss predicted seizure frequency. Conclusions: Patients with PHI carry a high risk of PTE decades after their injury, and so require long-term medical follow-up. Lesion location, lesion size, and lesion type were predictors of PTE. GLOSSARY ABLe = Analysis of Brain Lesions; AFQT = Armed Forces Qualification Test; AIR = Automated Image Registration; CHI = closed head injury; GAD = glutamic acid decarboxylase; PH1 = phase 1; PH2 = phase 2; PH3 = phase 3; PHI = penetrating head injury; PTE = posttraumatic epilepsy; TBI = traumatic brain injury; VHIS = Vietnam Head Injury Study; WAIS = Wechsler Adult Intelligence Scale. PMID:20644150

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PubMed

Boon, Paul; Vonck, Kristl; van Rijckevorsel, Kenou; El Tahry, Riem; Elger, Christian E; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate; Hamer, Hajo; Reuber, Markus; Kostov, Hrisimir; Legros, Benjamin; Noachtar, Soheyl; Weber, Yvonne G; Coenen, Volker A; Rooijakkers, Herbert; Schijns, Olaf E M G; Selway, Richard; Van Roost, Dirk; Eggleston, Katherine S; Van Grunderbeek, Wim; Jayewardene, Amara K; McGuire, Ryan M

2015-11-01

This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy.

PubMed

Ngo, Ly; Sperling, Michael R; Skidmore, Christopher; Mintzer, Scott; Nei, Maromi

2017-04-01

Frequent interictal epileptiform abnormalities may correlate with poor prognosis after temporal lobe resection for refractory epilepsy. To date, studies have focused on limited resections such as selective amygdalohippocampectomy and apical temporal lobectomy without hippocampectomy. However, it is unclear whether the frequency of spikes predicts outcome after standard anterior temporal lobectomy. Preoperative scalp video-EEG monitoring data from patients who subsequently underwent anterior temporal lobectomy over a three year period and were followed for at least one year were reviewed for the frequency of interictal epileptiform abnormalities. Surgical outcome for those patients with frequent spikes (>60/h) was compared with those with less frequent spikes. Additionally, spike frequency was evaluated as a continuous variable and correlated with outcome to determine if increased spike frequency correlated with worse outcome, as assessed by modified Engel Class outcome. Forty-seven patients (18 men, 29 women; mean age 40 years at surgery) were included. Forty-six patients had standard anterior temporal lobectomy (24 right, 22 left) and one had a modified left temporal lobectomy. There was no significant difference in seizure outcome between those with frequent (57% Class I) vs. those with less frequent (58% Class I) spikes. Increased spike frequency did not correlate with worse outcome. Greater than 20 complex partial seizures/month and generalized tonic-clonic seizures within one year of surgery correlated with worse outcome. This study suggests that absolute spike frequency does not predict seizure outcome after anterior temporal lobectomy unlike in selective procedures, and should not be used as a prognostic factor in this population. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows.

PubMed

Nguyen, Duc-Loc; Wimberley, Catriona; Truillet, Charles; Jego, Benoit; Caillé, Fabien; Pottier, Géraldine; Boisgard, Raphaël; Buvat, Irène; Bouilleret, Viviane

2018-06-01

Mesiotemporal lobe epilepsy is the most common type of drug-resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine which drugs, administered at which time point, will be most effective during the formation of this epileptic process. Neuroinflammation plays an important role in pathophysiological mechanisms in epilepsy, and therefore brain inflammation biomarkers such as translocator protein 18 kDa (TSPO) can be potent epilepsy biomarkers. TSPO is associated with reactive astrocytes and microglia. A unilateral intrahippocampal kainate injection mouse model can reproduce the defining features of human temporal lobe epilepsy with unilateral HS and the pattern of chronic pharmacoresistant temporal seizures. We hypothesized that longitudinal imaging using TSPO positron emission tomography (PET) with 18 F-DPA-714 could identify optimal treatment windows in a mouse model during the formation of HS. The model was induced into the right dorsal hippocampus of male C57/Bl6 mice. Micro-PET/computed tomographic scanning was performed before model induction and along the development of the HS at 7 days, 14 days, 1 month, and 6 months. In vitro autoradiography and immunohistofluorescence were performed on additional mice at each time point. TSPO PET uptake reached peak at 7 days and mostly related to microglial activation, whereas after 14 days, reactive astrocytes were shown to be the main cells expressing TSPO, reflected by a continuing increased PET uptake. TSPO-targeted PET is a highly potent longitudinal biomarker of epilepsy and could be of interest to determine the therapeutic windows in epilepsy and to monitor response to treatment. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Strategic hospital partnerships: improved access to care and increased epilepsy surgical volume.

PubMed

Vadera, Sumeet; Chan, Alvin Y; Mnatsankanyan, Lilit; Sazgar, Mona; Sen-Gupta, Indranil; Lin, Jack; Hsu, Frank P K

2018-05-01

OBJECTIVE Surgical treatment of patients with medically refractory focal epilepsy is underutilized. Patients may lack access to surgically proficient centers. The University of California, Irvine (UCI) entered strategic partnerships with 2 epilepsy centers with limited surgical capabilities. A formal memorandum of understanding (MOU) was created to provide epilepsy surgery to patients from these centers. METHODS The authors analyzed UCI surgical and financial data associated with patients undergoing epilepsy surgery between September 2012 and June 2016, before and after institution of the MOU. Variables collected included the length of stay, patient age, seizure semiology, use of invasive monitoring, and site of surgery as well as the monthly number of single-surgery cases, complex cases (i.e., staged surgeries), and overall number of surgery cases. RESULTS Over the 46 months of the study, a total of 104 patients underwent a total of 200 operations; 71 operations were performed in 39 patients during the pre-MOU period (28 months) and 129 operations were performed in 200 patients during the post-MOU period (18 months). There was a significant difference in the use of invasive monitoring, the site of surgery, the final therapy, and the type of insurance. The number of single-surgery cases, complex-surgery cases, and the overall number of cases increased significantly. CONCLUSIONS Partnerships with outside epilepsy centers are a means to increase access to surgical care. These partnerships are likely reproducible, can be mutually beneficial to all centers involved, and ultimately improve patient access to care.

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs.

PubMed

Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J; Fogel, Wieslawa A; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

2016-01-01

A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders.

Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

PubMed Central

Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

2016-01-01

A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: Linkage to convulsions and electroencephalography trait

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, A.W.; Delgado-Escueta, A.V.; Serratosa, J.M.

1995-08-01

Despite affecting 4 million Americans and 100-200 million persons worldwide, the precise molecular mechanisms of human epilepsies remain unknown. Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. In this epilepsy, electroencephalographic (EEG) 15-30 Hz multispikes produce myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Moreover, EEG 3.5-6 Hz multispike wave complexes appear in clinically asymptomatic family members. We first studied 38 members of a four-generation LA-Belize family with classical JME but with no pyknoleptic absences. Five living members had JME; four clinically asymptomatic members had EEG multispike wavemore » complexes. Pairwise analysis tightly linked microsatellites centromeric to HLA, namely D6S272 (peak lod score [Z{sub max}]=3.564-3.560 at male-female recombination [{theta}{sub m=f}]=0-0.001) and D6S257 (Z{sub max}=3.672-3.6667 at {theta}{sub m=f}=0-0.001), spanning 7 cM, to convulsive seizures and EEG multispike wave complexes. A recombination between D6S276 and D6S273 in one affected member placed the JME locus within or below HLA. Pairwise, multipoint, and recombination analyses in this large family independently proved that a JME gene is located in chromsome 6p, centromeric to HLA. We next screened, with the same chromosome 6p21.2-p11 short tandem-repeat polymorphic markers, seven multiplex pedigrees with classic JME. When lod scores for small multiplex families are added to lod scores of the LA-Belize pedigree, Z{sub max} values for D6S294 and D6S257 are >7 ({theta}{sub m=f}=0.000). Our results prove that in chromosome 6p21.2-p11 an epilepsy locus exists whose phenotype consists of classic JME with convulsions and/or EEG rapid multispike wave complexes. 31 refs., 6 figs., 4 tabs.« less

Mesial temporal lobe epilepsy - An overview of surgical techniques.

PubMed

Muzumdar, Dattatraya; Patil, Manoj; Goel, Atul; Ravat, Sangeeta; Sawant, Nina; Shah, Urvashi

2016-12-01

Mesial temporal lobe epilepsy is one of the commonest indications for epilepsy surgery. Presurgical evaluation for drug resistant epilepsy and identification of appropriate candidates for surgery is essential for optimal seizure freedom. The anatomy of mesial temporal lobe is complex and needs to be understood in the context of the advanced imaging, ictal and interictal Video_EEG monitoring, neuropsychology and psychiatric considerations. The completeness of disconnection of epileptogenic neural networks is paramount and is correlated with the extent of resection of the mesial temporal structures. In the Indian subcontinent, a standard but extended anterior temporal lobectomy is a viable option in view of the diverse socioeconomic, cultural and pathological considerations. The maximum utilization of epilepsy surgery services in this region is also a challenge. There is a need for regional comprehensive epilepsy care teams in a tertiary care academic hospital to form centers of excellence catering to a large population. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Add-on levetiracetam in children and adolescents with refractory epilepsy: results of an open-label multi-centre study.

PubMed

Callenbach, Petra M C; Arts, Willem Frans M; ten Houten, Robert; Augustijn, Paul; Gunning, W Boudewijn; Peeters, Els A J; Weber, Alma M; Stroink, Hans; Geerts, Yvette; Geerts, Ada T; Brouwer, Oebele F

2008-07-01

To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

A study on epileptic negative myoclonus in atypical benign partial epilepsy of childhood.

PubMed

Yang, Zhixian; Liu, Xiaoyan; Qin, Jiong; Zhang, Yuehua; Bao, Xinhua; Chang, Xingzhi; Wang, Shuang; Wu, Ye; Xiong, Hui

2009-04-01

To investigate the clinical and neurophysiological characteristics, particularly therapeutic considerations, of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy (ABPE) of childhood. From 1998 to 2006, 14/242 patients with benign children epilepsy with centrotemporal spikes (BECTS) were diagnosed as having ABPE with ENM. In all 14 patients, we performed video-EEG monitoring along with tests with the patient's arms outstretched; 6/14 patients were also simultaneously underwent surface electromyogram (EMG). ENM manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. In all cases, ENM developed after the onset of epilepsy and during antiepileptic drug therapy, and the appearance of ENM were corresponding to EEG findings of high-amplitude spikes followed by a slow wave in the contralateral motor areas with secondary generalization. This was further confirmed by time-locked silent EMG. During ENM occurrence or recurrence, habitual seizures and interictal discharges were exaggerated. In some patients, the changes in antiepileptic drug regimens in relation to ENM appearance included add-on therapy with carbamazepine, oxcarbazepine, and phenobarbital or withdrawal of valproate. ENM was controlled in most cases by administration of various combinations of valproate, clonazepam, and corticosteroids. The incidence of ENM or ABPE in our center was approximately 5.79%. A combination of video-EEG monitoring with the patient's arms outstretched and EMG is essential to identify ENM. The aggravation of habitual seizures and interictal discharges indicate ENM. Some antiepileptic drugs, such as carbamazepine, oxcarbazepine, and phenobarbital, may be related to ENM occurrence during spontaneous aggravation of ABPE. Various combinations of valproate, benzodiazepines, and corticosteroids are relatively effective for treating ENM that occurs in ABPE.

A case of epilepsy induced by eating or by visual stimuli of food made of minced meat.

PubMed

Mimura, Naoya; Inoue, Takeshi; Shimotake, Akihiro; Matsumoto, Riki; Ikeda, Akio; Takahashi, Ryosuke

2017-08-31

We report a 34-year-old woman with eating epilepsy induced not only by eating but also seeing foods made of minced meat. In her early 20s of age, she started having simple partial seizures (SPS) as flashback and epigastric discomfort induced by particular foods. When she was 33 years old, she developed SPS, followed by secondarily generalized tonic-clonic seizure (sGTCS) provoked by eating a hot dog, and 6 months later, only seeing the video of dumpling. We performed video electroencephalogram (EEG) monitoring while she was seeing the video of soup dumpling, which most likely caused sGTCS. Ictal EEG showed rhythmic theta activity in the left frontal to mid-temporal area, followed by generalized seizure pattern. In this patient, seizures were provoked not only by eating particular foods but also by seeing these. This suggests a form of epilepsy involving visual stimuli.

A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

PubMed

Miao, Jing; Feng, Jia-Chun; Zhu, Dan; Yu, Xue-Fan

2016-12-12

Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare. We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene. The present case report helps to better understand the clinical and genetic features of BMD.

Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures.

PubMed

Lhatoo, Samden D; Nei, Maromi; Raghavan, Manoj; Sperling, Michael; Zonjy, Bilal; Lacuey, Nuria; Devinsky, Orrin

2016-07-01

To describe the phenomenology of monitored sudden unexpected death in epilepsy (SUDEP) occurring in the interictal period where death occurs without a seizure preceding it. We report a case series of monitored definite and probable SUDEP where no electroclinical evidence of underlying seizures was found preceding death. Three patients (two definite and one probable) had SUDEP. They had a typical high SUDEP risk profile with longstanding intractable epilepsy and frequent generalized tonic-clonic seizures (GTCS). All patients had varying patterns of respiratory and bradyarrhythmic cardiac dysfunction with profound electroencephalography (EEG) suppression. In two patients, patterns of cardiorespiratory failure were similar to those seen in some patients in the Mortality in Epilepsy Monitoring Units Study (MORTEMUS). SUDEP almost always occur postictally, after GTCS and less commonly after a partial seizure. Monitored SUDEP or near-SUDEP cases without a seizure have not yet been reported in literature. When nonmonitored SUDEP occurs in an ambulatory setting without an overt seizure, the absence of EEG information prevents the exclusion of a subtle seizure. These cases confirm the existence of nonseizure SUDEP; such deaths may not be prevented by seizure detection-based devices. SUDEP risk in patients with epilepsy may constitute a spectrum of susceptibility wherein some are relatively immune, death occurs in others with frequent GTCS with one episode of seizure ultimately proving fatal, while in others still, death may occur even in the absence of a seizure. We emphasize the heterogeneity of SUDEP phenomena. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Emotional well-being in children with epilepsy: Family factors as mediators and moderators.

PubMed

Goodwin, Shane W; Wilk, Piotr; Karen Campbell, M; Speechley, Kathy N

2017-11-01

Our objective was to examine the relationships of factors associated with children's emotional well-being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors. Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well-being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). The relationships between clinical factors, family factors, and emotional well-being were assessed using multiple regression analyses. Family functioning, family stress, and repertoire of resources that the families had to adapt to stressful events were significantly associated with poor emotional well-being 2 years after diagnosis (p < 0.05) in the multivariable analysis. The effect of parental depressive symptoms was partially mediated by family functioning and family stress (p < 0.01 and p = 0.02, respectively). Family resources acted as a moderator in the relationship between severity of epilepsy and emotional well-being (p < 0.05). Based on our findings, efforts to strengthen the family environment may warrant attention. We suggest that clinicians take a family centered care approach by including families in treatment planning. Family centered care has been shown to improve family well-being and coping and in turn may reduce the impact of clinical factors on emotional well-being to improve long-term health-related quality of life. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage Gated Potassium Channel Mediated Seizures.

PubMed

Sirsi, Deepa; Dolce, Alison; Greenberg, Benjamin M; Thodeson, Drew

2016-01-01

There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis. We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization. This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes.

Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage Gated Potassium Channel Mediated Seizures

PubMed Central

Sirsi, Deepa; Dolce, Alison; Greenberg, Benjamin M; Thodeson, Drew

2017-01-01

Background There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis. Patient Description We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization. Conclusion This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes. PMID:29308451

A Population-Based Study of Long-term Outcomes of Cryptogenic Focal Epilepsy in Childhood: Cryptogenic Epilepsy is NOT Probably Symptomatic Epilepsy

PubMed Central

Wirrell, Elaine C; Grossardt, Brandon R; So, Elson L; Nickels, Katherine C

2011-01-01

Purpose To compare long-term outcome in a population-based group of children with cryptogenic vs symptomatic focal epilepsy diagnosed from 1980–2004 and to define the course of epilepsy in the cryptogenic group. Methods We identified all children residing in Olmsted County, MN, 1 month through 17 years with newly diagnosed, non-idiopathic focal epilepsy from 1980–2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long-term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings Of 359 children with newly-diagnosed epilepsy, 215 (60%) had non-idiopathic focal epilepsy. Of these, 206 (96%) were followed for more than 12 months. Ninety five children (46%) were classified as symptomatic. Median follow-up from diagnosis was similar in both groups, being 157 months (25%ile, 75%ile 89, 233) in the cryptogenic group vs 134 months (25%ile, 75%ile 78, 220) in the symptomatic group (p=0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long-term outcome was significantly better in those with cryptogenic vs symptomatic etiology (intractable epilepsy at last follow-up, 7% vs 40%, p<0.001; seizure-freedom at last follow-up, 81% vs 55%, p<0.001). Of those who achieved seizure-freedom at final follow-up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p=0.01). One third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure-free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly predict outcome in the cryptogenic group. Significance More than half of childhood non-idiopathic localization-related epilepsy is cryptogenic. This group has a significantly better long-term outcome than those with a symptomatic etiology, and should be distinguished from it. PMID:21320114

Vigabatrin pediatric dosing information for refractory complex partial seizures: results from a population dose-response analysis.

PubMed

Nielsen, Jace C; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G; Wesche, David L

2014-12-01

We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Safety profile of levetiracetam.

PubMed

Arroyo, Santiago; Crawford, Pamela

2003-05-01

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA.

PubMed

Villanueva, Vicente; López-Gomáriz, Elena; López-Trigo, Javier; Palau, Juan; García, Manuel; Villarroya, Teresa; Bonet, Macarena; Santafé, Consuelo

2012-03-01

There has been little long-term success with polytherapy for patients with refractory partial-onset epilepsy. The rational combination of antiepileptic drugs based on their mechanism of action may help improve treatment efficacy and tolerability. Lacosamide, a novel sodium channel blocker (SCB), was investigated in 158 patients with partial-onset epilepsy in the prospective, multicenter, observational, RELACOVA cohort study conducted in Spain. After 12 months' treatment with lacosamide, 47% of patients were responders (≥50% reduction in seizure frequency) and 24% were seizure free. Lacosamide was well tolerated; dizziness was the most frequent adverse event. Efficacy was better (responder rate, 65% vs 38%; seizure free rate, 35% vs 17%) and there was a lower adverse event rate (33% vs 58%) in patients receiving non-SCBs (n=49) versus those receiving SCBs (n=104) as concomitant therapy at baseline. Further investigation of lacosamide combination therapy is warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

Weight gain in children on oxcarbazepine monotherapy.

PubMed

Garoufi, Anastasia; Vartzelis, George; Tsentidis, Charalambos; Attilakos, Achilleas; Koemtzidou, Evangelia; Kossiva, Lydia; Katsarou, Eustathia; Soldatou, Alexandra

2016-05-01

Studies of the effect of oxcarbazepine (OXC) on body growth of children with epilepsy are rare and their results are controversial. To the contrary, many studies have shown significant weight gain following valproate (VPA) treatment. To prospectively evaluate the effect of OXC monotherapy on growth patterns of children with epilepsy and compare it with the effect of VPA monotherapy. Fifty-nine otherwise healthy children, aged 3.7-15.9 years, with primary generalized, partial or partial with secondary generalization seizure disorder, were included in the study. Twenty six children were placed on OXC and thirty three on VPA monotherapy. Body weight (BW), height and body mass index (BMI) as well as their standard deviation scores (SDS), were evaluated prior to as well as 8 months post initiation of OXC or VPA therapy. Eight months post OXC-treatment, BW, SDS-BW, BMI and SDS-BMI increased significantly. The increase was similar to that observed in the VPA group. An additional 15.4% of children in the OXC group and 21.2% in the VPA group became overweight or obese. The effect of both OXC and VPA therapy on linear growth did not reach statistical significance. Similarly to VPA, OXC monotherapy resulted in a significant weight gain in children with epilepsy. Careful monitoring for excess weight gain along with counseling on adapting a healthy lifestyle should be offered to children on OXC therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Validating the shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) in a sample of children with drug-resistant epilepsy.

PubMed

Conway, Lauryn; Widjaja, Elysa; Smith, Mary Lou; Speechley, Kathy N; Ferro, Mark A

2017-04-01

The aim of this study was to validate the newly developed shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) in a sample of children with drug-resistant epilepsy. Data came from 136 children enrolled in the Impact of Pediatric Epilepsy Surgery on Health-Related Quality of Life Study (PEPSQOL), a multicenter prospective cohort study. Confirmatory factor analysis was used to assess the higher-order factor structure of the QOLCE-55. Convergent and divergent validity was assessed by correlating subscales of the KIDSCREEN-27 with the QOLCE-55. Measurement equivalence of the QOLCE-55 was evaluated using multiple-group confirmatory factor analysis of children with drug-resistant epilepsy from PEPSQOL versus children with new-onset epilepsy from HERQULES (Health-Related Quality of Life in Children with Epilepsy Study). The higher-order factor structure of the QOLCE-55 demonstrated adequate fit: Comparative Fit Index (CFI) = 0.948; Tucker-Lewis Index (TLI) = 0.946; Root Mean Square of Approximation (RMSEA) = 0.060 (90% confidence interval [CI] 0.054-0.065); Weighted Root Mean Square Residuals (WRMR) = 1.247. Higher-order factor loadings were strong, ranging from λ = 0.74 to 0.81. Internal consistency reliability was excellent (α = 0.97, subscales α > 0.82). QOLCE-55 subscales demonstrated moderate to strong correlations with similar subscales of the KIDSCREEN-27 (ρ = 0.43-0.75) and weak to moderate correlations with dissimilar subscales (ρ = 0.25-0.42). The QOLCE-55 demonstrated partial measurement equivalence at the level of strict invariance - χ 2 (2,823) = 3,727.9, CFI = 0.961, TLI = 0.962, RMSEA = 0.049 (0.044, 0.053), WRMR = 1.834. The findings provide support for the factor structure of the QOLCE-55 and contribute to its robust psychometric profile as a reliable and valid measure. Researchers and health practitioners should consider the QOLCE-55 as a viable option for reducing respondent burden when assessing health-related quality of life in children with epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Epilepsy and the law--a view from Thailand.

PubMed

Locharernkul, Chaichon

2007-03-01

Patients with epilepsy often suffer social injustice in many societies. This is a review of current laws dealing with epilepsy and the consequences of this complex disease. The author looked at reported unjust legal and social acts resulting from epileptic seizures and their results. The author found that accusation of criminal acts, accidents while driving, and job loss are relatively common experiences for epileptics. Such events reflect lack of public understanding. There is inadequate legislation to protect epileptics. Most disturbing areas are ictal behavior misinterpreted as crime, driving while experiencing a seizure, and social discrimination. There is no law dealing with epilepsy in Thailand while considerable progress in this field has been made in Western countries. Epilepsy patients are inadequately protected by Thai law. There is an urgent need for education and campaigns for their rights focused on the public, the legal profession, and the health care professionals.

Causes of learning disability and epilepsy: a review.

PubMed

Prince, Elizabeth; Ring, Howard

2011-04-01

Although the association between learning disability and epilepsy is well known, until relatively recently specific processes underlying this association were relatively poorly understood. However, scientific advances in molecular biology are starting to guide researchers towards descriptions of genetic and pathophysiological processes that may explain why syndromes of epilepsy and learning disability often co-exist. This article will focus largely on three areas of advancing knowledge: insights gained from wider use of genome-wide array comparative genomic hybridization (aCGH), specific insights gained from detailed study of Rett syndrome and the role of abnormalities of astrocytic function in predisposing to both epilepsy and learning disability. The enormous complexity of the biological underpinnings of the co-occurrence of epilepsy and learning disability are becoming apparent. In the future it is likely that research into therapeutic approaches will include, amongst other approaches, investigations of gene structure and expression, the role of astrocytes and the stability of dendritic spines.

Microsensors and wireless system for monitoring epilepsy

NASA Astrophysics Data System (ADS)

Whitchurch, Ashwin K.; Ashok, B. H.; Kumaar, Raman V.; Sarukesi, K.; Jose, K. A.; Varadan, Vijay K.

2003-07-01

Epilepsy is a form of brain disorder caused by abnormal discharges of neurons. The most common manifestations of epilepsy are seizures which could affect visual, aural and motor abilities of a person. Absence epilepsy is a form of epilepsy common mostly in children. The most common manifestations of absence epilepsy are staring and transient loss of responsiveness. Also, subtle motor activities may occur. Due to the subtle nature of these symptoms, episodes of absence epilepsy may often go unrecognized for long periods of time or be mistakenly attributed to attention deficit disorder or daydreaming. Spells of absence epilepsy may last about 10 seconds and occur hundreds of times each day. Patients have no recollections of the events occurred during those seizures and will resume normal activity without any postictal symptoms. The EEG during such episodes of Absence epilepsy shows intermittent activity of 3 Hz generalized spike and wave complexes. As EEG is the only way of detecting such symptoms, it is required to monitor the EEG of the patient for a long time, usually the whole day. This requires that the patient be connected to the EEG recorder all the time and thus remain only in the bed. So, effectively the EEG is being monitored only when the patient is stationary. The wireless monitoring system described in this paper aims at eliminating this constraint and enables the physician to monitor the EEG when the patient resumes his normal activities. This approach could even help the doctor identify possible triggers of absence epilepsy.

Social determinants of health in epilepsy.

PubMed

Szaflarski, Magdalena

2014-12-01

Social factors have been identified as key drivers of epilepsy care, outcomes, and disparities, but there is a limited understanding of what these factors are and how they translate into disparities. This targeted review provides an overview of the social determinants of health framework and applies this perspective to the literature about social and psychosocial factors in epilepsy; a social determinants of health--epilepsy model is proposed. The key social determinants of health in epilepsy include socioeconomic status, race/ethnicity, age, and gender. For example, low socioeconomic status and minority status have been associated with a higher risk of epilepsy, more hospitalizations and emergency room visits (versus neurology services), antiepileptic drug nonadherence, and a lower rate of epilepsy surgery. Such differences in care/treatment and outcomes translate into health disparities, many of which are considered unjust (inequitable) and modifiable through social action. Other social determinants of health include structural and sociocultural contextual conditions (e.g., health economy, policy, and social stigma/discrimination) and mediating mechanisms including material (e.g., housing), behavioral/biological (e.g., adherence), psychosocial (e.g., perceived stigma), and health system (e.g., access) factors. There are complex relationships among social determinants of health in epilepsy, which remain poorly understood and hamper efforts to address and eliminate disparities in epilepsy care and outcomes. Further empirical work grounded in sound theory and robust methodologies is needed to identify points of intervention and design effective and socially acceptable solutions to any pervasive disparities in epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Epilepsy as a Network Disorder (1): What can we learn from other network disorders such as autistic spectrum disorder and mood disorders?

PubMed

Kanner, Andres M; Scharfman, Helen; Jette, Nathalie; Anagnostou, Evdokia; Bernard, Christophe; Camfield, Carol; Camfield, Peter; Legg, Karen; Dinstein, Ilan; Giacobbe, Peter; Friedman, Alon; Pohlmann-Eden, Bernd

2017-12-01

Epilepsy is a neurologic condition which often occurs with other neurologic and psychiatric disorders. The relation between epilepsy and these conditions is complex. Some population-based studies have identified a bidirectional relation, whereby not only patients with epilepsy are at increased risk of suffering from some of these neurologic and psychiatric disorders (migraine, stroke, dementia, autism, depression, anxiety disorders, Attention deficit hyperactivity disorder (ADHD), and psychosis), but also patients with these conditions are at increased risk of suffering from epilepsy. The existence of common pathogenic mechanisms has been postulated as a potential explanation of this phenomenon. To reassess the relationships between neurological and psychiatric conditions in general, and specifically autism, depression, Alzheimer's disease, schizophrenia, and epilepsy, a recent meeting brought together basic researchers and clinician scientists entitled "Epilepsy as a Network Disorder." This was the fourth in a series of conferences, the "Fourth International Halifax Conference and Retreat". This manuscript summarizes the proceedings on potential relations between Epilepsy on the one hand and autism and depression on the other. A companion manuscript provides a summary of the proceedings about the relation between epilepsy and Alzheimer's disease and schizophrenia, closed by the role of translational research in clarifying these relationships. The review of the topics in these two manuscripts will provide a better understanding of the mechanisms operant in some of the common neurologic and psychiatric comorbidities of epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

3D source localization of interictal spikes in epilepsy patients with MRI lesions

NASA Astrophysics Data System (ADS)

Ding, Lei; Worrell, Gregory A.; Lagerlund, Terrence D.; He, Bin

2006-08-01

The present study aims to accurately localize epileptogenic regions which are responsible for epileptic activities in epilepsy patients by means of a new subspace source localization approach, i.e. first principle vectors (FINE), using scalp EEG recordings. Computer simulations were first performed to assess source localization accuracy of FINE in the clinical electrode set-up. The source localization results from FINE were compared with the results from a classic subspace source localization approach, i.e. MUSIC, and their differences were tested statistically using the paired t-test. Other factors influencing the source localization accuracy were assessed statistically by ANOVA. The interictal epileptiform spike data from three adult epilepsy patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were then studied using both FINE and MUSIC. The comparison between the electrical sources estimated by the subspace source localization approaches and MRI lesions was made through the coregistration between the EEG recordings and MRI scans. The accuracy of estimations made by FINE and MUSIC was also evaluated and compared by R2 statistic, which was used to indicate the goodness-of-fit of the estimated sources to the scalp EEG recordings. The three-concentric-spheres head volume conductor model was built for each patient with three spheres of different radii which takes the individual head size and skull thickness into consideration. The results from computer simulations indicate that the improvement of source spatial resolvability and localization accuracy of FINE as compared with MUSIC is significant when simulated sources are closely spaced, deep, or signal-to-noise ratio is low in a clinical electrode set-up. The interictal electrical generators estimated by FINE and MUSIC are in concordance with the patients' structural abnormality, i.e. MRI lesions, in all three patients. The higher R2 values achieved by FINE than MUSIC indicate that FINE provides a more satisfactory fitting of the scalp potential measurements than MUSIC in all patients. The present results suggest that FINE provides a useful brain source imaging technique, from clinical EEG recordings, for identifying and localizing epileptogenic regions in epilepsy patients with focal partial seizures. The present study may lead to the establishment of a high-resolution source localization technique from scalp-recorded EEGs for aiding presurgical planning in epilepsy patients.

Economic analysis of an epilepsy outreach model of care in a university hospital setting.

PubMed

Maloney, Eimer; McGinty, Ronan N; Costello, Daniel J

2017-07-01

The prevalence of epilepsy in people with intellectual disability is higher than in the general population and prevalence rates increase with increasing levels of disability. Prevalence rates of epilepsy are highest among those living in residential care. The healthcare needs of people with intellectual disability and epilepsy are complex and deserve special consideration in terms of healthcare provision and access to specialist epilepsy clinics, which are usually held in acute hospital campuses. This patient population is at risk of suboptimal care because of significant difficulties accessing specialist epilepsy care which is typically delivered in the environs of acute hospitals. In 2014, the epilepsy service at Cork University Hospital established an Epilepsy Outreach Service providing regular, ambulatory outpatient follow up at residential care facilities in Cork city and county in an effort to improve access to care, reduce the burden and expense of patient and carer travel to hospital outpatient appointments, and to provide a dedicated specialist phone service for epilepsy related queries in order to reduce emergency room visits when possible. We present the findings of an economic analysis of the outreach service model of care compared to the traditional hospital outpatient service and demonstrate significant cost savings and improved access to care with this model. Ideally these cost savings should be used to develop novel ways to enhance epilepsy care for persons with disability. We propose that this model of care can be more suitable for persons with disability living in residential care who are at risk of losing access to specialist epilepsy care. Copyright © 2017 Elsevier Inc. All rights reserved.

From Classification to Epilepsy Ontology and Informatics

PubMed Central

Zhang, Guo-Qiang; Sahoo, Satya S; Lhatoo, Samden D

2012-01-01

Summary The 2010 International League Against Epilepsy (ILAE) classification and terminology commission report proposed a much needed departure from previous classifications to incorporate advances in molecular biology, neuroimaging, and genetics. It proposed an interim classification and defined two key requirements that need to be satisfied. The first is the ability to classify epilepsy in dimensions according to a variety of purposes including clinical research, patient care, and drug discovery. The second is the ability of the classification system to evolve with new discoveries. Multi-dimensionality and flexibility are crucial to the success of any future classification. In addition, a successful classification system must play a central role in the rapidly growing field of epilepsy informatics. An epilepsy ontology, based on classification, will allow information systems to facilitate data-intensive studies and provide a proven route to meeting the two foregoing key requirements. Epilepsy ontology will be a structured terminology system that accommodates proposed and evolving ILAE classifications, the NIH/NINDS Common Data Elements, the ICD systems and explicitly specifies all known relationships between epilepsy concepts in a proper framework. This will aid evidence based epilepsy diagnosis, investigation, treatment and research for a diverse community of clinicians and researchers. Benefits range from systematization of electronic patient records to multi-modal data repositories for research and training manuals for those involved in epilepsy care. Given the complexity, heterogeneity and pace of research advances in the epilepsy domain, such an ontology must be collaboratively developed by key stakeholders in the epilepsy community and experts in knowledge engineering and computer science. PMID:22765502

Violent somnambulism: a parasomnia of young men with stereotyped dream-like experiences.

PubMed

Szűcs, Anna; Kamondi, Anita; Zoller, Rezső; Barcs, Gábor; Szabó, Pál; Purebl, György

2014-07-01

To characterize a subgroup of arousal parasomnias associated with violent behavior in adults. A pilot study on clinical and polysomnographic data of 13 adult patients seen in a tertiary sleep center for the suspicion of arousal parasomnia associated with violence. Nine young patients (8 males 1 female) had a common pattern of abnormalities: similar 'claustrophobic' dream-like experiences and complex, vehement dream enactments; no REM sleep without atonia on polysomnography. We call this syndrome 'violent somnambulism'. The rest of the patients had alcoholic delirium, partial epilepsy, possible REM sleep behavior disorder and a single sleep walking episode provoked by a sleeping pill. Sleep related violence needs thorough diagnostic evaluation for preventing life-threatening consequences. Violent somnambulism appears to be a distinct NREM sleep-related overlap parasomnia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Localizing value of electrical source imaging: Frontal lobe, malformations of cortical development and negative MRI related epilepsies are the best candidates.

PubMed

Abdallah, Chifaou; Maillard, Louis G; Rikir, Estelle; Jonas, Jacques; Thiriaux, Anne; Gavaret, Martine; Bartolomei, Fabrice; Colnat-Coulbois, Sophie; Vignal, Jean-Pierre; Koessler, Laurent

2017-01-01

We aimed to prospectively assess the anatomical concordance of electric source localizations of interictal discharges with the epileptogenic zone (EZ) estimated by stereo-electroencephalography (SEEG) according to different subgroups: the type of epilepsy, the presence of a structural MRI lesion, the aetiology and the depth of the EZ. In a prospective multicentric observational study, we enrolled 85 consecutive patients undergoing pre-surgical SEEG investigation for focal drug-resistant epilepsy. Electric source imaging (ESI) was performed before SEEG. Source localizations were obtained from dipolar and distributed source methods. Anatomical concordance between ESI and EZ was defined according to 36 predefined sublobar regions. ESI was interpreted blinded to- and subsequently compared with SEEG estimated EZ. 74 patients were finally analyzed. 38 patients had temporal and 36 extra-temporal lobe epilepsy. MRI was positive in 52. 41 patients had malformation of cortical development (MCD), 33 had another or an unknown aetiology. EZ was medial in 27, lateral in 13, and medio-lateral in 34. In the overall cohort, ESI completely or partly localized the EZ in 85%: full concordance in 13 cases and partial concordance in 50 cases. The rate of ESI full concordance with EZ was significantly higher in (i) frontal lobe epilepsy (46%; p  = 0.05), (ii) cases of negative MRI (36%; p  = 0.01) and (iii) MCD (27%; p  = 0.03). The rate of ESI full concordance with EZ was not statistically different according to the depth of the EZ. We prospectively demonstrated that ESI more accurately estimated the EZ in subgroups of patients who are often the most difficult cases in epilepsy surgery: frontal lobe epilepsy, negative MRI and the presence of MCD.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2013-08-20

Nearly 30% of patients with epilepsy continue to have seizures in spite of several antiepileptic drug (AED) regimens. In such cases they are regarded as having refractory, or uncontrolled epilepsy.There is no universally accepted definition for uncontrolled or medically refractory epilepsy, but for the purpose of this review, we will consider seizures to be drug resistant if they failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. There are many types of surgery for refractory epilepsy with subpial transection being one. Our main aim is to determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (8 August 2013), The Cochrane Central Register of Controlled Trials (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8 August 2013). We did not impose any language restrictions. We considered all randomised and quasi-randomised parallel group studies either blinded or non-blinded. Two review authors (BK and SR) independently screened the trials identified by the search. The same two authors planned to independently assess the methodological quality of studies. If studies had been identified for inclusion, one author would have extracted the data and the other would have verified it. No relevant studies were found. There is no evidence to support or refute the use of subpial transection surgery for medically refractory cases of epilepsy. Well designed randomised controlled trials are needed in future to guide clinical practice.

The impact of maternal depressive symptoms on health-related quality of life in children with epilepsy: a prospective study of family environment as mediators and moderators.

PubMed

Ferro, Mark A; Avison, William R; Campbell, M Karen; Speechley, Kathy N

2011-02-01

To examine the impact of maternal depressive symptoms (DS) on health-related quality of life (HRQL) in children with new-onset epilepsy and to identify family factors that moderate and mediate this relationship during the first 24 months after epilepsy diagnosis. A sample of 339 mother-child dyads recruited from pediatric neurologists across Canada in the Health-related Quality of Life in Children with Epilepsy Study. Mothers' and neurologists' reports were collected at four times during the 24-month follow-up. Mothers' DS were measured using the Center for Epidemiological Studies Depression Scale (CES-D) and children's HRQL using the Quality of Life in Childhood Epilepsy (QOLCE). Data were modeled using individual growth curve modeling. Maternal DS were observed to have a negative impact on QOLCE scores at 24 months (β = -0.47, p < 0.0001) and the rate of change in QOLCE scores during follow-up (β = -0.04, p = 0.0250). This relationship was moderated by family resources (β = 0.25, p = 0.0243), and the magnitude of moderation varied over time (β = 0.09, p = 0.0212). Family functioning and demands partially mediated the impact of maternal DS on child HRQL (β = -0.07, p = 0.0007; β = -0.12, p = 0.0006). Maternal DS negatively impact child HRQL in new-onset epilepsy during the first 24 months after diagnosis. This relationship is moderated by family resources and mediated by family functioning and demands. By adopting family centered approaches, health care professionals may be able to intervene at the maternal or family level to promote more positive outcomes in children. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Readmission Following Surgical Resection for Intractable Epilepsy: Nationwide Rates, Causes, Predictors, and Outcomes.

PubMed

Rumalla, Kavelin; Smith, Kyle A; Arnold, Paul M; Schwartz, Theodore H

2018-06-04

Hospital readmissions can be detrimental to patients and may interfere with the potential benefits of the therapeutic procedure. Government agencies have begun to focus on reducing readmissions; however, the etiology of readmissions is lacking. To report the national rates, risk factors, and outcomes associated with 30- and 90-d readmissions following surgery for intractable epilepsy. We queried the Nationwide Readmissions Database from January to September 2013 using International Classification of Diseases, Ninth Edition, Clinical Modification codes to identify all patients with intractable epilepsy, who underwent hemispherectomy (01.52), brain lobectomy (01.53), amydalohippocampectomy, or partial lobectomy (01.59). Predictor variables included epilepsy type, presurgical diagnostic testing, surgery type, medical complications, surgical complications, and discharge disposition. In 1587 patients, the 30- and 90-d readmission rates were 11.5% and 16.8%, respectively. The most common reasons for readmission were persistent epilepsy, video electroencephalography monitoring, postoperative infection, and postoperative central nervous system complication. In multivariable analysis, risk factors associated with both 30- and 90-d readmission were Medicare payer status, lowest quartile of median income, depression, hemispherectomy, and postoperative complications (P < .05). The only unique predictor of 30-d readmission was small bedsize hospital (P = .001). Readmissions within 30 d were associated with longer length of stay (6.8 vs 5.8 d), greater costs ($18 660 vs $15 515), and increased adverse discharges (26.4% vs 21.8%). Following epilepsy surgery, most readmissions that occurred within 30 d can be attributed to management of persistent epilepsy and predicted by Medicare payer status, depression, and complications. These data can assist the clinician in preventing readmissions and assist policy makers determine which admissions are potentially avoidable.

Brain Structure and Organization Five Decades After Childhood Onset Epilepsy

PubMed Central

Garcia-Ramos, Camille; Bobholz, Sam; Dabbs, Kevin; Hermann, Bruce; Joutsa, Juho; Rinne, Juha O.; Karrasch, Mira; Prabhakaran, Vivek; Shinnar, Shlomo; Sillanpää, Matti

2017-01-01

The purpose of this project was to characterize brain structure and organization in persons with active and remitted childhood onset epilepsy 50 years after diagnosis compared to healthy controls. Participants from a population-based investigation of uncomplicated childhood onset epilepsy were followed up 5 decades later. Forty-one participants had a history of childhood onset epilepsy (mean age of onset= 5.2 yrs, current chronological age= 56.0 yrs) and were compared to 48 population-based controls (mean age= 55.9 yrs). Of the epilepsy participants, 8 had persisting active epilepsy and in 33 the epilepsy had remitted. All participants underwent 3T MRI with subsequent vertex analysis of cortical volume, thickness, surface area and gyral complexity. In addition, cortical and subcortical volumes, including regions of the frontal, parietal, temporal, and occipital lobes, and subcortical structures including amygdala, thalamus, and hippocampus, were analyzed using graph theory techniques. There were modest group differences in traditional vertex-based analyses of cortical volume, thickness, surface area and gyral index, as well as across volumes of subcortical structures, after correction for multiple comparisons. Graph theory analyses revealed suboptimal topological structural organization with enhanced network segregation and reduced global integration in the epilepsy participants compared to controls, these patterns significantly more extreme in the active epilepsy group. Furthermore, both groups with epilepsy presented a greater number of higher Z-score regions in betweenness centrality (BC) than lower Z-score regions compared to controls. Also, contrary to the group with remitted epilepsy, patients with active epilepsy presented most of their high BC Z-score regions in subcortical areas including the amygdala, thalamus, hippocampus, pallidum and accumbens. Overall, this population-based investigation of long term outcome (5 decades) of childhood onset epilepsy reveals persisting abnormalities, especially when examined by graph theoretical measurements, and provides new insights into the very long term outcomes of active and remitted epilepsy. PMID:28370719

Affective disorders and functional (non-epileptic) seizures in persons with epilepsy.

PubMed

Johnson, Keith A; Macfarlane, Matthew D; Looi, Jeffrey Cl

2016-12-01

This paper aims to describe the prevalence, assessment and management of affective disorders as well as functional (non-epileptic) seizures in people with epilepsy. This paper comprises a selective review of the literature of the common affective manifestations of epilepsy. Affective disorders are the most common psychiatric comorbidity seen in people with epilepsy and assessment and management parallels that of the general population. Additionally, people with epilepsy may experience higher rates of mood instability, irritability and euphoria, classified together as a group, interictal dysphoric disorder and resembling an unstable bipolar Type II disorder. Functional seizures present unique challenges in terms of identification of the disorder and a lack of specific management. Given their high prevalence, it is important to be able to recognise affective disorders in people with epilepsy. Management principles parallel those in the general population with specific caution exercised regarding the potential interactions between antidepressant medications and antiepileptic drugs. Functional seizures are more complex and require a coordinated approach involving neurologists, psychiatrists, general practitioners, nursing and allied health. There is very limited evidence to guide psychological and behavioural interventions for neurotic disorders in epilepsy and much more research is needed. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Noninvasive testing, early surgery, and seizure freedom in tuberous sclerosis complex.

PubMed

Wu, J Y; Salamon, N; Kirsch, H E; Mantle, M M; Nagarajan, S S; Kurelowech, L; Aung, M H; Sankar, R; Shields, W D; Mathern, G W

2010-02-02

The unambiguous identification of the epileptogenic tubers in individuals with tuberous sclerosis complex (TSC) can be challenging. We assessed whether magnetic source imaging (MSI) and coregistration of (18)fluorodeoxyglucose PET (FDG-PET) with MRI could improve the identification of the epileptogenic regions noninvasively in children with TSC. In addition to standard presurgical evaluation, 28 children with intractable epilepsy from TSC referred from 2000 to 2007 had MSI and FDG-PET/MRI coregistration without extraoperative intracranial EEG. Based on the concordance of test results, 18 patients with TSC (64%) underwent surgical resection, with the final resection zone confirmed by intraoperative electrocorticography. Twelve patients are seizure free postoperatively (67%), with an average follow-up of 4.1 years. Younger age at surgery and shorter seizure duration were associated with postoperative seizure freedom. Conversely, older age and longer seizure duration were linked with continued seizures postoperatively or prevented surgery because of nonlateralizing or bilateral independent epileptogenic zones. Complete removal of presurgery MSI dipole clusters correlated with postoperative seizure freedom. Magnetic source imaging and (18)fluorodeoxyglucose PET/MRI coregistration noninvasively localized the epileptogenic zones in many children with intractable epilepsy from tuberous sclerosis complex (TSC), with 67% seizure free postoperatively. Seizure freedom after surgery correlated with younger age and shorter seizure duration. These findings support the concept that early epilepsy surgery is associated with seizure freedom in children with TSC and intractable epilepsy.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

PubMed

Mühlebner, Angelika; van Scheppingen, Jackelien; Hulshof, Hanna M; Scholl, Theresa; Iyer, Anand M; Anink, Jasper J; van den Ouweland, Ans M W; Nellist, Mark D; Jansen, Floor E; Spliet, Wim G M; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A; Feucht, Martha; Aronica, Eleonora

2016-01-01

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex

PubMed Central

Hulshof, Hanna M.; Scholl, Theresa; Iyer, Anand M.; Anink, Jasper J.; van den Ouweland, Ans M. W.; Nellist, Mark D.; Jansen, Floor E.; Spliet, Wim G. M.; Krsek, Pavel; Benova, Barbora; Zamecnik, Josef; Crino, Peter B.; Prayer, Daniela; Czech, Thomas; Wöhrer, Adelheid; Rahimi, Jasmin; Höftberger, Romana; Hainfellner, Johannes A.; Feucht, Martha; Aronica, Eleonora

2016-01-01

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC. PMID:27295297

Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

PubMed Central

Coan, Ana C.; Campos, Brunno M.; Yasuda, Clarissa L.; Kubota, Bruno Y.; Bergo, Felipe PG.; Guerreiro, Carlos AM.; Cendes, Fernando

2014-01-01

Objective Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS). Methods We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures. Results Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions. Conclusion Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process. PMID:24475055

The long-term outcomes of epilepsy surgery

PubMed Central

Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections. PMID:29768433

The long-term outcomes of epilepsy surgery.

PubMed

Mohan, Midhun; Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1-27). Kaplan-Meier estimates showed that 47% (95% CI 40-58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31-45) at 10 years after surgery. 74% (95% CI 69-80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64-77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections.

Seroprevalence and Associated Risk Factors of Toxocariasis among College Students in Taipei City, Taiwan

PubMed Central

FU, Chung-Jung; KAO, Cheng-Yan; LEE, Yueh-Lun; LIAO, Chien-Wei; CHEN, Po-Ching; CHUANG, Ting-Wu; WANG, Ying-Chin; CHOU, Chia-Mei; HUANG, Ying-Chie; NAITO, Toshio; FAN, Chia-Kwung

2015-01-01

Background: Infection by Toxocara spp. is known to be significantly associated with partial epilepsy. It has become popular for people to raise dogs/cats as pets and consume roasted meat/viscera, and the status of Toxocara spp. infection, epilepsy awareness, and associated risk factors among the general population are currently unknown in Taiwan. Methods: A seroepidemiological investigation among 203 college students (CSs), consisting of 110 males and 93 females with an average age of 21.5 ± 1.2 years, was conducted in 2009 in Taipei City. A Western blot analysis based on excretory-secretory antigens derived from Toxocara canis larvae (TcESs) was applied to determine the positivity of serum immunoglobulin G antibodies. A self-administered questionnaire was also given to obtain information about demographic characteristics, epilepsy awareness, and risk factors. A logistic regression model was applied for the statistical analysis using SPSS software. Results: The overall seropositive rate of Toxocara spp. infection was 8.4% (17/203). As to epilepsy awareness, a non-significantly higher seroprevalence was found in CSs who claimed to "know" about epilepsy compared to those who did not know (P > 0.05). Conclusions: It appears that appropriate educational programs are urgently needed to provide correct knowledge related to the prevention and control measures against Toxocara spp. infections to avoid potential threats by this parasite to the general population in Taiwan. PMID:26622304

Epileptic seizure predictors based on computational intelligence techniques: a comparative study with 278 patients.

PubMed

Alexandre Teixeira, César; Direito, Bruno; Bandarabadi, Mojtaba; Le Van Quyen, Michel; Valderrama, Mario; Schelter, Bjoern; Schulze-Bonhage, Andreas; Navarro, Vincent; Sales, Francisco; Dourado, António

2014-05-01

The ability of computational intelligence methods to predict epileptic seizures is evaluated in long-term EEG recordings of 278 patients suffering from pharmaco-resistant partial epilepsy, also known as refractory epilepsy. This extensive study in seizure prediction considers the 278 patients from the European Epilepsy Database, collected in three epilepsy centres: Hôpital Pitié-là-Salpêtrière, Paris, France; Universitätsklinikum Freiburg, Germany; Centro Hospitalar e Universitário de Coimbra, Portugal. For a considerable number of patients it was possible to find a patient specific predictor with an acceptable performance, as for example predictors that anticipate at least half of the seizures with a rate of false alarms of no more than 1 in 6 h (0.15 h⁻¹). We observed that the epileptic focus localization, data sampling frequency, testing duration, number of seizures in testing, type of machine learning, and preictal time influence significantly the prediction performance. The results allow to face optimistically the feasibility of a patient specific prospective alarming system, based on machine learning techniques by considering the combination of several univariate (single-channel) electroencephalogram features. We envisage that this work will serve as benchmark data that will be of valuable importance for future studies based on the European Epilepsy Database. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Screening LGI1 in a cohort of 26 lateral temporal lobe epilepsy patients with auditory aura from Turkey detects a novel de novo mutation.

PubMed

Kesim, Yesim F; Uzun, Gunes Altiokka; Yucesan, Emrah; Tuncer, Feyza N; Ozdemir, Ozkan; Bebek, Nerses; Ozbek, Ugur; Iseri, Sibel A Ugur; Baykan, Betul

2016-02-01

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is an autosomal dominant epileptic syndrome characterized by focal seizures with auditory or aphasic symptoms. The same phenotype is also observed in a sporadic form of lateral temporal lobe epilepsy (LTLE), namely idiopathic partial epilepsy with auditory features (IPEAF). Heterozygous mutations in LGI1 account for up to 50% of ADLTE families and only rarely observed in IPEAF cases. In this study, we analysed a cohort of 26 individuals with LTLE diagnosed according to the following criteria: focal epilepsy with auditory aura and absence of cerebral lesions on brain MRI. All patients underwent clinical, neuroradiological and electroencephalography examinations and afterwards they were screened for mutations in LGI1 gene. The single LGI1 mutation identified in this study is a novel missense variant (NM_005097.2: c.1013T>C; p.Phe338Ser) observed de novo in a sporadic patient. This is the first study involving clinical analysis of a LTLE cohort from Turkey and genetic contribution of LGI1 to ADLTE phenotype. Identification of rare LGI1 gene mutations in sporadic cases supports diagnosis as ADTLE and draws attention to potential familial clustering of ADTLE in suggestive generations, which is especially important for genetic counselling. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional definition of seizure provides new insight into post-traumatic epileptogenesis.

PubMed

D'Ambrosio, Raimondo; Hakimian, Shahin; Stewart, Tessandra; Verley, Derek R; Fender, Jason S; Eastman, Clifford L; Sheerin, Aaron H; Gupta, Puneet; Diaz-Arrastia, Ramon; Ojemann, Jeffrey; Miller, John W

2009-10-01

Experimental animals' seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8-2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8-2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8-2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed, with common duration-based arbitrary definitions resulting in artificially prolonged latencies for epileptogenesis. Finally, we present four human examples of electrocorticography capturing short (<2 s), stereotyped, neocortically generated EEEs that occurred in the same ictal sites as obvious complex partial seizures, were electrographically similar to rat EEEs and were not noted during scalp electroencephalography. When occurring in the motor cortex, these short EEEs were accompanied by ictal behaviour detectable with simultaneous surface electromyography. These data demonstrate that short (<2 s) focal recurrent spontaneous EEEs are seizures in both rats and humans, that they are undetectable by scalp electroencephalography, and that they are typically associated with subtle and easily missed behavioural correlates. These findings define the earliest identifiable markers of progressive post-traumatic epilepsy in the rat, with implications for mechanistic and prophylactic studies, and should prompt a re-evaluation of the concept of post-traumatic silent period in both animals and humans.

Functional definition of seizure provides new insight into post-traumatic epileptogenesis

PubMed Central

Hakimian, Shahin; Stewart, Tessandra; Verley, Derek R.; Fender, Jason S.; Eastman, Clifford L.; Sheerin, Aaron H.; Gupta, Puneet; Diaz-Arrastia, Ramon; Ojemann, Jeffrey; Miller, John W.

2009-01-01

Experimental animals’ seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8–2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8–2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8–2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed, with common duration-based arbitrary definitions resulting in artificially prolonged latencies for epileptogenesis. Finally, we present four human examples of electrocorticography capturing short (<2 s), stereotyped, neocortically generated EEEs that occurred in the same ictal sites as obvious complex partial seizures, were electrographically similar to rat EEEs and were not noted during scalp electroencephalography. When occurring in the motor cortex, these short EEEs were accompanied by ictal behaviour detectable with simultaneous surface electromyography. These data demonstrate that short (<2 s) focal recurrent spontaneous EEEs are seizures in both rats and humans, that they are undetectable by scalp electroencephalography, and that they are typically associated with subtle and easily missed behavioural correlates. These findings define the earliest identifiable markers of progressive post-traumatic epilepsy in the rat, with implications for mechanistic and prophylactic studies, and should prompt a re-evaluation of the concept of post-traumatic silent period in both animals and humans. PMID:19755519

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

PubMed Central

Tang, Fei; Hartz, Anika M. S.; Bauer, Björn

2017-01-01

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy. PMID:28729850

Clinical stabilisation with lacosamide of mood disorder comorbid with PTSD and fronto-temporal epilepsy.

PubMed

Cuomo, Ilaria; Kotzalidis, Georgios D; De Filippis, Sergio

2017-08-23

Mood disorders are often complicated by comorbidity with epilepsy. Anxiety and personality disorders may worsen prognosis and treatment outcome. Lacosamide has been recently introduced as adjunctive treatment for partial epilepsy. Its mechanism consists of selective slow inactivation of voltage-gated sodium channels, thus promoting an extended stabilisation of cell membranes. Antiepileptic drugs have been largely used since the 1950s in psychiatry as mood stabilisers due to their membrane stabilising and anti-kindling effects. Like lithium, antiepileptic drugs are first choice treatment for Bipolar and Cyclothymic Disorders. We tested the efficacy of the most recent antiepileptic medication, lacosamide, in a patient with simultaneously occurring cyclothymic disorder, severe post-traumatic stress disorder, and fronto-temporal epilepsy. Lacosamide was titrated up to 200 mg/day, added on ongoing 750 mg/day lithium, 15 mg/day oral aripiprazole then switched to 400 mg/month long-acting aripiprazole, and 2 mg/day N-desmethyldiazepam. We observed EEG normalisation one month later, along with reduced anxiety and an additive effect to lithium-induced stabilisation of mood fluctuations since the second week of lacosamide addition. Further studies with this drug in the bipolar spectrum are warranted.

Computational models of epileptiform activity.

PubMed

Wendling, Fabrice; Benquet, Pascal; Bartolomei, Fabrice; Jirsa, Viktor

2016-02-15

We reviewed computer models that have been developed to reproduce and explain epileptiform activity. Unlike other already-published reviews on computer models of epilepsy, the proposed overview starts from the various types of epileptiform activity encountered during both interictal and ictal periods. Computational models proposed so far in the context of partial and generalized epilepsies are classified according to the following taxonomy: neural mass, neural field, detailed network and formal mathematical models. Insights gained about interictal epileptic spikes and high-frequency oscillations, about fast oscillations at seizure onset, about seizure initiation and propagation, about spike-wave discharges and about status epilepticus are described. This review shows the richness and complementarity of the various modeling approaches as well as the fruitful contribution of the computational neuroscience community in the field of epilepsy research. It shows that models have progressively gained acceptance and are now considered as an efficient way of integrating structural, functional and pathophysiological data about neural systems into "coherent and interpretable views". The advantages, limitations and future of modeling approaches are discussed. Perspectives in epilepsy research and clinical epileptology indicate that very promising directions are foreseen, like model-guided experiments or model-guided therapeutic strategy, among others. Copyright © 2015 Elsevier B.V. All rights reserved.

Current role of perampanel in pediatric epilepsy.

PubMed

De Liso, Paola; Moavero, Romina; Coppola, Giangennaro; Curatolo, Paolo; Cusmai, Raffaella; De Sarro, Giovambattista; Franzoni, Emilio; Vigevano, Federico; Verrotti, Alberto

2017-06-02

Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.

Epilepsy in TSC: certain etiology does not mean certain prognosis.

PubMed

Vignoli, Aglaia; La Briola, Francesca; Turner, Katherine; Scornavacca, Giulia; Chiesa, Valentina; Zambrelli, Elena; Piazzini, Ada; Savini, Miriam Nella; Alfano, Rosa Maria; Canevini, Maria Paola

2013-12-01

Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial. We reviewed the clinical characteristics of patients with TSC who were regularly followed since 2000 at the San Paolo Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts we collected data about age at epilepsy onset, seizure frequency and seizure type, history of infantile spasms (IS), epileptic syndrome, evolution to refractory epilepsy or to seizure freedom and/or medication freedom, electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings, cognitive outcome, and genetic background. Among the 160 subjects (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure-free, and 59 (36.9%) had drug-resistant epilepsy. Most seizure-free patients had a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their lives. Epilepsy onset in the first year of life with IS and/or focal seizures was characteristic of the drug-resistant group of patients, as well as cognitive impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients, 4.4%) experienced a seizure only once; all of them had normal cognition. Although epilepsy management can be challenging in TSC, more than one third of patients had their seizures controlled: through monotherapy in 56% and by polytherapy in 32%. Moreover, 12% of the patients became seizure-free and were off medication. Identifying predictive features of epilepsy and cognitive outcome can ensure better management for patients with TSC and delineate genotype-phenotype correlations. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Computational models of epilepsy.

PubMed

Stefanescu, Roxana A; Shivakeshavan, R G; Talathi, Sachin S

2012-12-01

Approximately 30% of epilepsy patients suffer from medically refractory epilepsy, in which seizures can not controlled by the use of anti-epileptic drugs (AEDs). Understanding the mechanisms underlying these forms of drug-resistant epileptic seizures and the development of alternative effective treatment strategies are fundamental challenges for modern epilepsy research. In this context, computational modeling has gained prominence as an important tool for tackling the complexity of the epileptic phenomenon. In this review article, we present a survey of computational models of epilepsy from the point of view that epilepsy is a dynamical brain disease that is primarily characterized by unprovoked spontaneous epileptic seizures. We introduce key concepts from the mathematical theory of dynamical systems, such as multi-stability and bifurcations, and explain how these concepts aid in our understanding of the brain mechanisms involved in the emergence of epileptic seizures. We present a literature survey of the different computational modeling approaches that are used in the study of epilepsy. Special emphasis is placed on highlighting the fine balance between the degree of model simplification and the extent of biological realism that modelers seek in order to address relevant questions. In this context, we discuss three specific examples from published literature, which exemplify different approaches used for developing computational models of epilepsy. We further explore the potential of recently developed optogenetics tools to provide novel avenue for seizure control. We conclude with a discussion on the utility of computational models for the development of new epilepsy treatment protocols. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

[The effect of bemitil on the parameters of lipid peroxidation and nitrogen metabolism in epilepsy in children].

PubMed

Mikhałlov, I B; Guzeva, V I; Sharf, M Ia; Basharina, O B; Chałka, N A

1997-01-01

Epileptic patients given phenobarbital (3 mg/kg, n = 8) or finlepsin (20 mg/kg, n = 7) were found to have a statistically significant increase (p < 0.05) in the parameters of the lipid peroxidation end product malonic dialdehyde in the erythrocytes (3.34 +/- 1.13 mumol/liter) and blood plasma (0.099 +/- 0.04 mumol/liter) in comparison to the control group (n = 9; 1.58 +/- 0.96 mumol/liter and 0.045 +/- 0.02 mumol/liter, respectively). The urea level (6.7 +/- 1.28 mumol/liter) and the ammonia level (31.59 +/- 10.46 mumol/liter) increase were statistically insignificant as compared to the controls (5.76 +/- 0.66 mumol/liter and 26.41 +/- 5.96 mumol/liter, respectively). Bemitil (n = -7) in a dose of 20 mg/kg reduced in 10 days the amount of malonic dialdehyde in the erythrocytes (1.57 +/- 0.61 mumol/liter, p < 0.05) and plasma (0.043 +/- 0.02 mumol/liter, p < 0.05) as well as the amount of urea (3.76 +/- 0.96 mumol/liter,) and ammonia p < 0.05 and ammonia (18.17 +/- 2.02 mumol/liter, p < 0.05) in the blood. A favorable therapeutic effect (lesser frequency of seizures and lesser asthenia of the of the children) was observed at the same time. The frequency of paroxysms reduced to 50% in 4 patients (2 with complex-partial seizures, one with absence, and one with simple-partial seizures) and to 75-% in the fifth patient with complex-partial seizures. The therapeutic effect in the 6th and 7th patients could not be evaluated.

Effect-site concentration of propofol target-controlled infusion at loss of consciousness in intractable epilepsy patients receiving long-term antiepileptic drug therapy.

PubMed

Choi, Eun Mi; Choi, Seung Ho; Lee, Min Huiy; Ha, Sang Hee; Min, Kyeong Tae

2011-07-01

Propofol dose requirement for loss of consciousness (LOC) in epilepsy patients would be probably affected by increasing factors [development of tolerance, up-regulated γ-aminobutyric acid (GABAA) receptors, or antiepileptic activity of propofol] and reducing factors [synergistic interaction between propofol and antiepileptic drugs (AEDs) or reduced neuronal mass in cortex] in complex and counteracting ways. Therefore, we determined the effect-site concentration (Ce) of propofol for LOC in intractable epilepsy patients receiving chronic AEDs in comparison with non-epilepsy patients. Nineteen epilepsy patients receiving long-term AEDs therapy and 20 non-epilepsy patients, with the age of 20 to 65 years, were enrolled. The epilepsy patients took their prescribed AEDs until the morning of the operation. Ce of propofol for LOC was determined with isotonic regression method with bootstrapping approach following Dixon's up-and-down allocation. The study was carried out before surgical stimulation. Isotonic regression showed that estimated Ce50 and Ce95 of propofol for LOC were lower in epilepsy group [2.88 μg/mL (83% confidence interval, 2.82-3.13 μg/mL) and [3.43 μg/mL (95% confidence interval, 3.28-3.47 μg/mL)] than in non-epilepsy group [3.38 μg/mL (83% confidence interval, 3.17-3.63 μg/mL) and 3.92 μg/mL (95% confidence interval, 3.80-3.97 μg/mL)] with bootstrapping approach. Mean Ce50 of propofol of epilepsy group was also lower than that of non-epilepsy group without statistical significance (2.8240.19 μg/mL vs 3.16±0.38 μg/mL, P=0.056). For anesthetic induction of epilepsy patients with propofol target-controlled infusion, Ce may need to be reduced by 10% to 15% compared with non-epilepsy patients.

Epilepsy services in Ireland: 'A survey of people with epilepsy in relation to satisfaction, preferences and information provision'.

PubMed

Bennett, Louise; Bergin, Michael; Gooney, Martina; Doherty, Colin P; Synnott, Cara; Wells, John S G

2015-07-01

A challenge facing modern health care systems is to develop and implement new models of service that deliver increased capacity while providing a higher-quality, more cost-effective service within resource constraints. Incorporating the experience of people with epilepsy must be seen as central to the effectiveness of service design and delivery. This paper, therefore, reports the views of people with epilepsy with regards to health service delivery in Ireland. A cross-sectional descriptive survey design involving both quantitative and qualitative items was administered to a convenience sample of one hundred and two people with epilepsy (n=102) attending an epilepsy specialist centre. Despite high levels of satisfaction with hospital and primary care, participants offered several suggestions to improve healthcare delivery, such as: less delay in accessing specialist care and hospital appointments; better communication; and easier access to investigatory services. Findings demonstrate that for people with epilepsy the burden of the disorder is substantial and complex encompassing social, psychological and structural difficulties. Poor information provision particularly among women is reported. Furthermore, a lack of empowerment in people with epilepsy is highlighted. This study has implications for the reform and development of epilepsy services in relation to practice, education and research. It provides a basis for an evaluation of current practice and identifies opportunities for future service reorganization to improve the quality and efficiency of healthcare provision. Copyright © 2015 Elsevier B.V. All rights reserved.

Paroxysmal arousal in epilepsy associated with cingulate hyperperfusion.

PubMed

Vetrugno, R; Mascalchi, M; Vella, A; Della Nave, R; Provini, F; Plazzi, G; Volterrani, D; Bertelli, P; Vattimo, A; Lugaresi, E; Montagna, P

2005-01-25

A patient with nocturnal frontal lobe epilepsy characterized by paroxysmal motor attacks during sleep had brief paroxysmal arousals (PAs), complex episodes of nocturnal paroxysmal dystonia, and epileptic nocturnal wandering since childhood. Ictal SPECT during an episode of PA demonstrated increased blood flow in the right anterior cingulate gyrus and cerebellar cortex with hypoperfusion in the right temporal and frontal associative cortices.

[Autism, epilepsy and tuberous sclerosis complex: a functional model linked to mTOR pathway].

PubMed

García-Peñas, Juan José; Carreras-Sááez, Inmaculada

2013-02-22

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. Brain disorders are the origin of more frequent and severe problems and include infantile spasms, intractable epilepsy, brain tumors, cognitive disabilities, and autism. TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. AIM. To review the etiopathogenic mechanisms and the natural course of the association of autism and epilepsy in TSC. Both the clinical and the neuroimaging findings of TSC, including early onset epilepsy and the localization of cortical tubers in the temporal lobes, and the molecular understanding of the mTOR signaling pathway, not only involved in cell growth, but also in synaptogenesis, synaptic plasticity and neuronal functioning, have suggested a multimodal origin of autism in these patients. A greater understanding of the pathogenetic mechanisms underlying autism in TSC could help in devising targeted and potentially more effective treatment strategies. Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

PubMed Central

Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

2017-01-01

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies.

PubMed

Greene, Amanda E; Todorova, Mariana T; Seyfried, Thomas N

2003-08-01

Brain cells are metabolically flexible because they can derive energy from both glucose and ketone bodies (acetoacetate and beta-hydroxybutyrate). Metabolic control theory applies principles of bioenergetics and genome flexibility to the management of complex phenotypic traits. Epilepsy is a complex brain disorder involving excessive, synchronous, abnormal electrical firing patterns of neurons. We propose that many epilepsies with varied etiologies may ultimately involve disruptions of brain energy homeostasis and are potentially manageable through principles of metabolic control theory. This control involves moderate shifts in the availability of brain energy metabolites (glucose and ketone bodies) that alter energy metabolism through glycolysis and the tricarboxylic acid cycle, respectively. These shifts produce adjustments in gene-linked metabolic networks that manage or control the seizure disorder despite the continued presence of the inherited or acquired factors responsible for the epilepsy. This hypothesis is supported by information on the management of seizures with diets including fasting, the ketogenic diet and caloric restriction. A better understanding of the compensatory genetic and neurochemical networks of brain energy metabolism may produce novel antiepileptic therapies that are more effective and biologically friendly than those currently available.

A targeted resequencing gene panel for focal epilepsy.

PubMed

Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

2016-04-26

We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

When epilepsy may have changed history: Antônio Moreira César as the commander of the third expedition in the war of Canudos.

PubMed

Yacubian, Elza Márcia Targas

2003-06-01

Colonel Antônio Moreira César, the Commander of the third Expedition against Canudos (1896-1897), nicknamed "head-chopper", was considered an implacable military man, a synonym of ferocity and extreme brutality against his adversaries. Therefore, he was nominated the Commander of an expedition considered almost invincible. Since his 30's he presented epileptic seizures, which increased in frequency and severity on his way to Canudos. After several well-documented episodes and probably considering himself the winner in anticipation, he ordered a premature and almost ingenuous attack against Canudos. His misjudging is attributed to the effect of successive seizures. He was shot and killed on the very first day of that battle and his expedition had a horrible and unexpected end. Based on the descriptions of his biographer we discuss the nature of his disease probably characterized by focal seizures with elementary and complex visual hallucinations followed by language deficits and episodes of complex partial seizures and secondary generalization and its role in this episode of Brazilian history.

Anti-Neuronal Autoantibodies in Both Drug Responsive and Resistant Focal Seizures with Unknown Cause.

PubMed

Gozubatik-Celik, Gokcen; Ozkara, Cigdem; Ulusoy, Canan; Gunduz, Aysegul; Delil, Sakir; Yeni, Naz; Tuzun, Erdem

2017-09-01

and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients. Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies. Age at examination, gender, age at onset, seizure frequency, risk factors, seizure precipitants, and type of seizures were noted. Plasma obtained from patients was frozen at -80°C and analysed for autoantibodies against VGKC-complex, VGCC, GAD, LGI1, CASPR2, NMDA, AMPA and GABAB receptors with immunocytochemistry and radioimmunoassay as required. Thirteen (13.8%) patients, but none of the controls, had antibodies (p=0.003). Antibodies were directed against the uncharacterized components of VGKC-complex in 5 patients (5.3%), GAD in 4 patients (4.2%), NMDA-R in 1 patient (1%), AMPA-R in 1 patient (1%) and both GAD and VGKC-complex in 2 patients (2.1%). Prognosis of epilepsy, in subsequent follow-up, did not correlate to general presence of anti-neuronal antibodies with slightly more patients with antibodies epilepsy control than without (76.9% vs. 69.1%, not-statistically significant. Three patients with suspected active autoimmunity and epilepsy who were treated, showed a response to treatment with a reduction in the seizure frequency. Although most clinical features were identical between seropositive and seronegative patient groups, seropositive patients were more likely to have inflammatory/autoimmune disorders in their medical history. In keeping with previous studies, we have shown anti-neuronal antibodies in a proportion of focal epilepsy patients. Although autoimmunity might merely occur as a bystander effect in many chronic neurological disorders, association of anti-neuronal antibodies with good response to immunotherapy and coexisting autoimmune disorders suggests that anti-neuronal autoimmunity might participate in seizure formation at least in a subgroup of focal epilepsy patients. Immunity may play a role in some patients with unknown etiology regardless of prognosis and immunmodulatuar treatment may be helpful in seropositive group. Copyright © 2017 Elsevier B.V. All rights reserved.

Epilepsy in children with tuberous sclerosis complex: Chance of remission and response to antiepileptic drugs.

PubMed

Overwater, Iris E; Bindels-de Heus, Karen; Rietman, André B; Ten Hoopen, Leontine W; Vergouwe, Yvonne; Moll, Henriette A; de Wit, Marie-Claire Y

2015-08-01

To describe treatment and outcome of epilepsy in children with tuberous sclerosis complex (TSC). Seventy-one children with TSC and epilepsy treated at the ENCORE TSC Expertise Center between 1988 and 2014 were included. Patient characteristics and duration and effectiveness of antiepileptic treatments were extracted from our clinical database. Correlations were made between recurrence of seizures after response to treatment, and several patient characteristics. Median age at time of inclusion was 9.4 years (range 0.9-18.0). Seizure history showed that 55 children (77%) of 71 became seizure-free for longer than 1 month, and 21 (30%) of 71 for longer than 24 months. Remission of seizures was associated with higher IQ, and a trend was observed between seizure remission and age at onset of seizures. A total of 19 antiepileptic drugs (AEDs) were used. Valproic acid, vigabatrin, levetiracetam, and carbamazepine were used most frequently. Nonpharmacologic therapies (ketogenic diet, epilepsy surgery, and vagus nerve stimulation) were used 13 times. Epilepsy surgery was most effective, with four of five children becoming seizure-free. AEDs prescribed as first and second treatment were most effective. Valproic acid was prescribed most frequently as first and second treatment, followed by vigabatrin. Thirty-one children had infantile spasms, preceded by focal seizures in 18 children (58%). Vigabatrin was used by 29 children (94%), and was first treatment in 15 (48%). Vigabatrin was more effective than other AEDs when prescribed as first treatment. We showed that, although 77% of children with epilepsy due to TSC reached seizure remission, usually after their first or second AED, this was sustained for at least 24 months in only 38%. Almost half of those with 24 months of remission later had relapse of seizures. Our results support vigabatrin as first choice drug, and show the need for better treatment options for these children. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Postnatal reduction of tuberous sclerosis complex 1 expression in astrocytes and neurons causes seizures in an age-dependent manner.

PubMed

Zou, Jia; Zhang, Bo; Gutmann, David H; Wong, Michael

2017-12-01

Epilepsy is one of the most prominent symptoms of tuberous sclerosis complex (TSC), a genetic disorder, and may be related to developmental defects resulting from impaired TSC1 or TSC2 gene function in astrocytes and neurons. Inactivation of the Tsc1 gene driven by a glial-fibrillary acidic protein (GFAP) promoter during embryonic brain development leads to widespread pathologic effects on astrocytes and neurons, culminating in severe, progressive epilepsy in mice (Tsc1 GFAP -Cre mice). However, the developmental timing and cellular specificity relevant to epileptogenesis in this model has not been well defined. The present study evaluates the effect of postnatal Tsc1 gene inactivation on pathologic features of astrocytes and neurons and development of epilepsy. An inducible Tsc1 knock-out mouse was created utilizing a tamoxifen-driven GFAP-CreER line (Tsc1 GFAP -Cre ER mice) with TSC1 reduction induced postnatally at 2 and 6 weeks of age, and compared to conventional Tsc1 GFAP -Cre mice with prenatal TSC1 reduction. Western blotting, immunohistochemistry, histology, and video-electroencephalography (EEG) assessed mechanistic target of rapamycin (mTOR) pathway activation, astrogliosis, neuronal organization, and spontaneous seizures, respectively. Tsc1 gene inactivation at 2 weeks of age was sufficient to cause astrogliosis and mild epilepsy in Tsc1 GFAP -Cre ER mice, but the phenotype was much less severe than that observed with prenatal Tsc1 gene inactivation in Tsc1 GFAP -Cre mice. Both astrocytes and neurons were affected by prenatal and postnatal Tsc1 gene activation to a degree similar to the severity of epilepsy, suggesting that both cellular types may contribute to epileptogenesis. These findings support a model in which the developmental timing of TSC1 loss dictates the severity of neuronal and glial abnormalities and resulting epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Methods and utility of EEG-fMRI in epilepsy

PubMed Central

Lemieux, Louis; Chaudhary, Umair Javaid

2015-01-01

Brain activity data in general and more specifically in epilepsy can be represented as a matrix that includes measures of electrophysiology, anatomy and behaviour. Each of these sub-matrices has a complex interaction depending upon the brain state i.e., rest, cognition, seizures and interictal periods. This interaction presents significant challenges for interpretation but also potential for developing further insights into individual event types. Successful treatments in epilepsy hinge on unravelling these complexities, and also on the sensitivity and specificity of methods that characterize the nature and localization of underlying physiological and pathological networks. Limitations of pharmacological and surgical treatments call for refinement and elaboration of methods to improve our capability to localise the generators of seizure activity and our understanding of the neurobiology of epilepsy. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI), by potentially circumventing some of the limitations of EEG in terms of sensitivity, can allow the mapping of haemodynamic networks over the entire brain related to specific spontaneous and triggered epileptic events in humans, and thereby provide new localising information. In this work we review the published literature, and discuss the methods and utility of EEG-fMRI in localising the generators of epileptic activity. We draw on our experience and that of other groups, to summarise the spectrum of information provided by an increasing number of EEG-fMRI case-series, case studies and group studies in patients with epilepsy, for its potential role to elucidate epileptic generators and networks. We conclude that EEG-fMRI provides a multidimensional view that contributes valuable clinical information to localize the epileptic focus with potential important implications for the surgical treatment of some patients with drug-resistant epilepsy, and insights into the resting state and cognitive network dynamics. PMID:25853087

Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

PubMed

Barba, Carmen; Specchio, Nicola; Guerrini, Renzo; Tassi, Laura; De Masi, Salvatore; Cardinale, Francesco; Pellacani, Simona; De Palma, Luca; Battaglia, Domenica; Tamburrini, Gianpiero; Didato, Giuseppe; Freri, Elena; Consales, Alessandro; Nozza, Paolo; Zamponi, Nelia; Cesaroni, Elisabetta; Di Gennaro, Giancarlo; Esposito, Vincenzo; Giulioni, Marco; Tinuper, Paolo; Colicchio, Gabriella; Rocchi, Raffaele; Rubboli, Guido; Giordano, Flavio; Lo Russo, Giorgio; Marras, Carlo Efisio; Cossu, Massimo

2017-10-01

The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014. A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014. Retrospective data on 527 surgical procedures were collected. The most frequent surgical approaches were temporal lobe resections and disconnections (133, 25.2%) and extratemporal lesionectomies (128, 24.3%); the most frequent etiologies were FCD II (107, 20.3%) and glioneuronal tumors (105, 19.9%). Volumes of surgeries increased over time independently from the age at surgery and the epilepsy surgery center. Engel class I was achieved in 73.6% of patients (range: 54.8 to 91.7%), with no significant changes between 2008 and 2014. Univariate analyses showed a decrease in the proportion of temporal resections and tumors and an increase in the proportion of FCDII, while multivariate analyses revealed an increase in the proportion of extratemporal surgeries over time. A higher proportion of temporal surgeries and tumors and a lower proportion of extratemporal and multilobar surgeries and of FCD were observed in low (<50surgeries/year) versus high-volume centers. There was a high variability across centers concerning pre- and postsurgical evaluation protocols, depending on local expertise and facilities. This survey reveals an increase in volume and complexity of pediatric epilepsy surgery in Italy between 2008 and 2014, associated with a stable seizure outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings.

PubMed

Baysal-Kirac, Leyla; Tuzun, Erdem; Erdag, Ece; Ulusoy, Canan; Vanli-Yavuz, Ebru Nur; Ekizoglu, Esme; Peach, Sian; Sezgin, Mine; Bebek, Nerses; Gurses, Candan; Gokyigit, Aysen; Vincent, Angela; Baykan, Betul

2016-03-01

Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

Epilepsy: habilitation and rehabilitation.

PubMed

Marks, Warren A; Hernandez, Angel; Gabriel, Marsha

2003-06-01

Rehabilitation represents not only a distinct field of medicine, but also a philosophical and practical treatment approach that can be applied to a variety of chronic disorders. Neurology encompasses many chronic disorders, making it ideal for the application of rehabilitation principles in daily practice. Epilepsy offers a unique opportunity to incorporate rehabilitation principles into the management of a complex medical disorder. Epilepsy is an evolving disease process that changes with the maturation of the central nervous system. The rehabilitative model provides the framework for a dynamic treatment plan to meet the changing needs of the child with epilepsy through the social and developmental changes of childhood, adolescence, and adulthood. The development of epilepsy may complicate the recovery from many acute and chronic conditions that affect the central nervous system. The rehabilitation process must address these many aspects of the disease process and its sequelae. This makes neurologists uniquely qualified to manage the rehabilitation team. The impact of the therapeutic milieu on the recovery process may be as important as any specific medical or surgical intervention.

Thyroid hormones: Possible roles in epilepsy pathology.

PubMed

Tamijani, Seyedeh Masoumeh Seyedhoseini; Karimi, Benyamin; Amini, Elham; Golpich, Mojtaba; Dargahi, Leila; Ali, Raymond Azman; Ibrahim, Norlinah Mohamed; Mohamed, Zahurin; Ghasemi, Rasoul; Ahmadiani, Abolhassan

2015-09-01

Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

PICK1 uncoupling from mGluR7a causes absence-like seizures

PubMed Central

Bertaso, Federica; Zhang, Chuansheng; Scheschonka, Astrid; de Bock, Frédéric; Fontanaud, Pierre; Marin, Philippe; Huganir, Richard L; Betz, Heinrich; Bockaert, Joël; Fagni, Laurent; Lerner-Natoli, Mireille

2009-01-01

Absence epilepsy is a neurological disorder that causes a recurrent loss of consciousness and generalized spike-and-wave discharges on an electroencephalogram (EEG). The role of metabotropic glutamate receptors (mGluRs) and associated scaffolding proteins in absence epilepsy has been unclear to date. We investigated a possible role for these proteins in absence epilepsy, focusing on the mGluR7a receptor and its PDZ-interacting protein, protein interacting with C kinase 1 (PICK1), in rats and mice. Injection of a cell-permeant dominant-negative peptide or targeted mutation of the mGluR7a C terminus, both of which disrupt the interaction between the receptor and PDZ proteins, caused behavioral symptoms and EEG discharges that are characteristic of absence epilepsy. Inactivation of the Pick1 gene also facilitated pharmacological induction of the absence epilepsy phenotype. The cortex and thalamus, which are known to participate in absence epilepsy, were involved, but the hippocampus was not. Our results indicate that disruption of the mGluR7a-PICK1 complex is sufficient to induce absence epilepsy—like seizures in rats and mice, thus providing, to the best of our knowledge, the first animal model of metabotropic glutamate receptor—PDZ protein interaction in absence epilepsy. PMID:18641645

Lunisolar tidal waves, geomagnetic activity and epilepsy in the light of multivariate coherence.

PubMed

Mikulecky, M; Moravcikova, C; Czanner, S

1996-08-01

The computed daily values of lunisolar tidal waves, the observed daily values of Ap index, a measure of the planetary geomagnetic activity, and the daily numbers of patients with epileptic attacks for a group of 28 neurology patients between 1987 and 1992 were analyzed by common, multiple and partial cross-spectral analysis to search for relationships between periodicities in these time series. Significant common and multiple coherence between them was found for rhythms with a period length over 3-4 months, in agreement with seasonal variations of all three variables. If, however, the coherence between tides and epilepsy was studied excluding the influence of geomagnetism, two joint infradian periodicities with period lengths of 8.5 and 10.7 days became significant. On the other hand, there were no joint rhythms for geomagnetism and epilepsy when the influence of tidal waves was excluded. The result suggests a more primary role of gravitation, compared with geomagnetism, in the multivariate process studied.

Successful Treatment of Refractory Seizures With Rufinamide in Children With Schizencephaly: Report of 3 Cases.

PubMed

Verrotti, Alberto; Loiacono, Giulia; Rossi, Alessandra; Tartaro, Armando; Delli Pizzi, Andrea; Coppola, Giangennaro

2015-07-01

Schizencephaly is an uncommon malformation of cortical development. Patients with schizencephaly present with a broad range of severe neurologic symptoms including pharmacoresistant epilepsy. Rufinamide is a new antiepileptic drug approved for use as adjunctive therapy of seizures associated with Lennox-Gastaut syndrome and it is also effective for refractory partial seizures. We report 3 cases of pediatric patients aged 7.2, 8.1, and 10.1 years, respectively, with intractable epilepsy associated with bilateral open-lip schizencephaly and septo-optic dysplasia. The follow-up ranged from 3.8 to 4.1 years. In our patients, the introduction of rufinamide as adjunctive drug led to a dramatic decline in the number of seizures and an improvement in EEG epileptic activity without side effects. Rufinamide seems to be efficacious and safe in patients with epileptic encephalopathies associated with pharmacoresistant epilepsy; further and larger clinical reports and controlled studies could confirm the usefulness of this anticonvulsant drug. © The Author(s) 2014.

[Prospective multicenter study on long-term ketogenic diet therapy for intractable childhood epilepsy].

PubMed

2013-04-01

To evaluate the efficacy and safety of long-term ketogenic diet (KD) on the children with intractable epilepsy. This was a prospective, open-label study of intractable epilepsy patients treated with the classic KD with a lipid-to-nonlipid ratio 4:1 between October 2004 and July 2011 at five Chinese epilepsy centers. A total of 299 patients were enrolled. The patients were divided into different groups according to age (including the below-1-year-old group, 1-to-3-year-old group, 3-to-6-year-old group, 6-to-10-year-old group, and over-10-year-old group), etiology (cryptogenic epilepsy, symptomatic epilepsy, and idiopathic epilepsy), and the seizure types (included infantile spasm, Lennox-Gastaut syndrome, Ohtahara syndrome, tuberous sclerosis, Dravet syndrome, generalized epilepsy, and partial epilepsy). Parents were assigned to write seizure diaries which recorded the seizure presentations, tolerability, and complications associated with the KD. Patients' weight and height were measured every week. Blood β-hydroxybutyric acid, blood sugar, and urinary ketone bodies were monitored closely. Patients were followed up through telephone calls by the nutritionists every month and regular outpatient visits or hospitalizations were recommended at all time-points which included the third, sixth and twelfth month after initiation. Efficacy was measured through seizure frequency. The variables related to the efficacy were also analyzed. SPSS 17.0 was used for all statistical analysis. At 3, 6, and 12 months after initiation, 65.9%, 44.8%, and 26.4% patients remained on the diet, and 37.4%, 26.1%, and 20.4% had a > 50% reduction in their seizure frequency, including 21.7%, 10.7%, and 11.0% who became seizure free, respectively. At 24 months after initiation, 29 patients remained on the diet, and 28 patients had a > 90% seizure reduction, including five became seizure free. At 36 months after initiation, 7 patients remained on the diet, and all of them had a > 90% seizure reduction, including five became seizure free. No significant variables were related to the efficacy. Most complications were mild and reversible by conservative treatment. Gastrointestinal disturbances were the main complications, which included vomiting, diarrhea, constipation, and abdominal cramp. Severe complications occurred in four cases, including severe metabolic disturbances and severe pneumonia. The KD is a safe and effective alternative therapy for intractable childhood epilepsy.

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

Diagnosing and Solving School Learning Disabilities in Epilepsy: Part 2--A List of Causes

ERIC Educational Resources Information Center

Mittan, Robert J.

2010-01-01

The possible causes of learning difficulties in children with epilepsy are long and complex. In order to see that a child is given an adequate evaluation, an understanding of what these many causes are and how those causes may be interrelated is necessary. This article discusses the first three of the six categories of the causes: (1) Organic; (2)…

Defining Early Markers of Neurodevelopmental Disorders in Infants With TSC

DTIC Science & Technology

2013-10-01

in (1) children with autism and tuberous sclerosis complex and (2) children with temporal lobe tubers. This study is the first to quantify atypical...Furthermore, we hypothesize that it is the dynamic interplay between aberrant functional connectivity and physiological stressors, such as epilepsy ...neurodevelopmental disorders in children with TSC, particularly the interaction between clinical factors (such as epilepsy or tuber burden) and cognitive and

Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

PubMed

Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

2017-06-29

Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events. IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than both current first-line treatments carbamazepine and lamotrigine; lamotrigine performed better than all other treatments (aside from levetiracetam), and carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure types (moderate- to high-quality evidence).Generally, direct evidence and network meta-analysis estimates (direct plus indirect evidence) were numerically similar and consistent with confidence intervals of effect sizes overlapping.The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders. Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.

Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

PubMed

Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

2017-12-15

Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', 'time to first seizure post-randomisation', and 'occurrence of adverse events'. We presented all time-to-event outcomes as Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). We performed pairwise meta-analysis of head-to-head comparisons between drugs within trials to obtain 'direct' treatment effect estimates and we performed frequentist network meta-analysis to combine direct evidence with indirect evidence across the treatment network of 10 drugs. We investigated inconsistency between direct estimates and network meta-analysis via node splitting. Due to variability in methods and detail of reporting adverse events, we have not performed an analysis. We have provided a narrative summary of the most commonly reported adverse events. IPD was provided for at least one outcome of this review for 12,391 out of a total of 17,961 eligible participants (69% of total data) from 36 out of the 77 eligible trials (47% of total trials). We could not include IPD from the remaining 41 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions.We were able to calculate direct treatment effect estimates for between half and two thirds of comparisons across the outcomes of the review, however for many of the comparisons, data were contributed by only a single trial or by a small number of participants, so confidence intervals of estimates were wide.Network meta-analysis showed that for the primary outcome 'Time to withdrawal of allocated treatment,' for individuals with partial seizures; levetiracetam performed (statistically) significantly better than current first-line treatment carbamazepine and other current first-line treatment lamotrigine performed better than all other treatments (aside from levetiracetam); carbamazepine performed significantly better than gabapentin and phenobarbitone (high-quality evidence). For individuals with generalised onset seizures, first-line treatment sodium valproate performed significantly better than carbamazepine, topiramate and phenobarbitone (moderate- to high-quality evidence). Furthermore, for both partial and generalised onset seizures, the earliest licenced treatment, phenobarbitone seems to perform worse than all other treatments (moderate- to high-quality evidence).Network meta-analysis also showed that for secondary outcomes 'Time to 12-month remission of seizures' and 'Time to six-month remission of seizures,' few notable differences were shown for either partial or generalised seizure types (moderate- to high-quality evidence). For secondary outcome 'Time to first seizure,' for individuals with partial seizures; phenobarbitone performed significantly better than both current first-line treatments carbamazepine and lamotrigine; carbamazepine performed significantly better than sodium valproate, gabapentin and lamotrigine. Phenytoin also performed significantly better than lamotrigine (high-quality evidence). In general, the earliest licenced treatments (phenytoin and phenobarbitone) performed better than the other treatments for both seizure types (moderate- to high-quality evidence).Generally, direct evidence and network meta-analysis estimates (direct plus indirect evidence) were numerically similar and consistent with confidence intervals of effect sizes overlapping.The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders. Overall, the high-quality evidence provided by this review supports current guidance (e.g. NICE) that carbamazepine and lamotrigine are suitable first-line treatments for individuals with partial onset seizures and also demonstrates that levetiracetam may be a suitable alternative. High-quality evidence from this review also supports the use of sodium valproate as the first-line treatment for individuals with generalised tonic-clonic seizures (with or without other generalised seizure types) and also demonstrates that lamotrigine and levetiracetam would be suitable alternatives to either of these first-line treatments, particularly for those of childbearing potential, for whom sodium valproate may not be an appropriate treatment option due to teratogenicity.

The challenge and promise of anti-epileptic therapy development in animal models

PubMed Central

Simonato, Michele; Brooks-Kayal, Amy R; Engel, Jerome; Galanopoulou, Aristea S; Jensen, Frances E; Moshé, Solomon L; O’Brien, Terence J; Pitkanen, Asla; Wilcox, Karen S; French, Jacqueline A

2016-01-01

Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies—complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed. PMID:25127174

Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

PubMed

Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

2016-01-01

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

75 FR 4407 - The Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... premarket approval application for the Deep Brain Stimulation System for Epilepsy sponsored by Medtronic...-onset seizures (affecting only a part of the brain when they begin), with or without secondary... a partial-onset seizure that later spreads to the whole brain. ``Refractory'' to antiepileptic...

Development of lacosamide for the treatment of partial-onset seizures

PubMed Central

Doty, Pamela; Hebert, David; Mathy, Francois-Xavier; Byrnes, William; Zackheim, James; Simontacchi, Kelly

2013-01-01

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug–drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic–clonic seizures in those with idiopathic generalized epilepsy. PMID:23859801

Left Frontal Meningioangiomatosis Associated with Type IIIc Focal Cortical Dysplasia Causing Refractory Epilepsy and Literature Review.

PubMed

Roux, Alexandre; Mellerio, Charles; Lechapt-Zalcman, Emmanuelle; Still, Megan; Zerah, Michel; Bourgeois, Marie; Pallud, Johan

2018-06-01

We report the surgical management of a lesional drug-resistant epilepsy caused by a meningioangiomatosis associated with a type IIIc focal cortical dysplasia located in the left supplementary motor area in a young male patient. A first anatomically based partial surgical resection was performed on an 11-year-old under general anesthesia without intraoperative mapping, which allowed for postoperative seizure control (Engel IA) for 6 years. The patient then exhibited intractable right sensatory and aphasic focal onset seizures despite 2 appropriate antiepileptic drugs. A second functional-based surgical resection was performed using intraoperative corticosubcortical functional mapping with direct electrical stimulation under awake conditions. A complete surgical resection was performed, and a left partial supplementary motor area syndrome was observed. At 6 months postoperatively, the patient is seizure free (Engel IA) with an ongoing decrease in antiepileptic drug therapy. Intraoperative functional brain mapping can be applied to preserve the brain function and networks around a meningioangiomatosis to facilitate the resection of potentially epileptogenic perilesional dysplastic cortex and to tailor the extent of resection to functional boundaries. Copyright © 2018 Elsevier Inc. All rights reserved.

Getting the best outcomes from epilepsy surgery

PubMed Central

Vakharia, Vejay N.; Witt, Juri‐Alexander; Elger, Christian E.; Staba, Richard; Engel, Jerome

2018-01-01

Neurosurgery is an underutilized treatment that can potentially cure drug‐refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug‐refractory focal epilepsies. Ann Neurol 2018;83:676–690 PMID:29534299

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

Praxis induction. Definition, relation to epilepsy syndromes, nosological and prognostic significance. A focused review.

PubMed

Yacubian, Elza Márcia; Wolf, Peter

2014-04-01

There is increasing awareness that reflex epileptic mechanisms provide unique insight into ictogenesis in human epilepsies. Several of the described triggers have in common that they imply complex visuomotor coordination and decision-making; they are today regarded as variations of one principle, i.e. praxis induction (PI). This focused review considers PI from the aspects of history and delineation, clinical and electroencephalographic presentation, syndromatic relations, prevalence, mechanisms of ictogenesis and nosological implications, treatment and prognosis. We reviewed a series of published articles and case reports on PI in order to clarify clinical and electroencephalographic findings, treatment and outcome. Findings of both induction and inhibition by the same stimuli suggest widening the reflex epilepsy concept into a broader one of epilepsies with exogenous modification of ictogenesis. PI is closely related to juvenile myoclonic epilepsy (JME) where hyperexcitability and hyperconnectivity of the entire network of visuomotor coordination seem to provide the precondition for eliciting reflex myocloni in the musculature active in the precipitating task. The conclusions on ictogenesis derived from PI support the concept of JME as a system disorder of the brain. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

[The presentation of disease and medicine in film. Film stereotypes of epilepsy].

PubMed

Maio, G

2001-03-01

Our presentation examines historical changes in the contextualisation of epilepsy by the media. In movies, one may note a particularly long-lasting predominance of traditional complexes of the significance of epilepsy. Epilepsy as an hereditary disease, as a degenerative illness, as a cause of criminality. These are the motifs, established myths, which lived on in movies long beyond the time at which scientific opinion had distanced itself from them. A radical change in the manner of presentation of epilepsy began in the late sixties. From that time on, not only the connotation of epilepsy was altered, but, above all, the presentation of the patient, who henceforth, according to the changing processes of society was shown as a self-aware and active shaper of his life. Thus it is precisely the development during the last fifteen years, in which numerous sensitive motion pictures have tackled the inner perspective of the patient, movies having not only ceased to pass on the established myths, but become promoters of new attitudes toward disease. With this type of representation of disease and patient, due to its direct and broad effect, motion pictures can spread new realities in a manner hardly possible for other media.

Psychosis of epilepsy: a multifaceted neuropsychiatric disorder.

PubMed

Kanner, Andres M; Rivas-Grajales, Ana Maria

2016-06-01

Psychosis of epilepsy (POE) is a term applied to a group of psychotic disorders with a distinct phenomenology in which potential etiopathogenic mechanisms are believed to be closely related to a seizure disorder. POE can present as interictal psychotic episodes, which may often differ semiologically from primary schizophrenic disorder. They may present as ictal or postictal psychotic episodes and may be the expression of an iatrogenic process to pharmacologic and/or surgical interventions.Epilepsy and POE have a complex and bidirectional relation, as not only are patients with epilepsy at greater risk of developing a psychotic disorder, but patients with a primary psychotic disorder are also at greater risk of developing epilepsy. The prevalence of POE is more than 7 times higher than the frequency of primary schizophreniform disorders in the general population. While POE has been associated with focal epilepsy of temporal and frontal lobe origin, its etiology and pathophysiology of POE have yet to be established.The treatment of all forms of POE, with the exception of ictal psychotic episodes, requires the use of antipsychotic drugs, preferably the atypical antipsychotic agents with a very low or negligible potential to lower the seizure threshold (eg, risperidone, apiprazole), starting at a low dose with stepwise increments.

Deficits in oculomotor performance in pediatric epilepsy

PubMed Central

Asato, Miya R.; Nawarawong, Natalie; Hermann, Bruce; Crumrine, Patricia; Luna, Beatriz

2010-01-01

Summary Purpose Given evidence of limitations in neuropsychological performance in epilepsy, we probed the integrity of components of cognition, including speed of processing, response inhibition, and spatial working memory supporting executive function in pediatric epilepsy patients and matched controls. Methods A total of 44 pairs of controls and medically treated pediatric epilepsy patients with no known brain pathology completed cognitive oculomotor tasks, computerized neuropsychological testing, and psychiatric assessment. Results Patients showed slower reaction time to initiate a saccadic response compared to controls but had intact saccade accuracy. Cognitively driven responses including response inhibition were impaired in the patient group. Patients had increased incidence of comorbid psychopathology but comorbidity did not predict worse functioning compared to patients with no ADHD. Epilepsy type and medication status were not predictive of outcome. More complex neuropsychological performance was impaired in tasks requiring visual memory and sequential processing which was correlated with inhibitory control and antisaccade accuracy. Discussion Pediatric epilepsy may be associated with vulnerabilities that specifically undermine speed of processing and response inhibition but not working memory and may underlie known neuropsychological performance limitations. This particular profile of abnormalities may be associated with seizure-mediated compromises in brain maturation early in development. PMID:21087246

Long-Term Clinical and Electroencephalography (EEG) Consequences of Idiopathic Partial Epilepsies.

PubMed

Dörtcan, Nimet; Tekin Guveli, Betul; Dervent, Aysin

2016-05-03

BACKGROUND Idiopathic partial epilepsies of childhood (IPE) affect a considerable proportion of children. Three main electroclinical syndromes of IPE are the Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS), Panayiotopoulos Syndrome (PS), and Childhood Epilepsy with Occipital Paroxysms (CEOP). In this study we investigated the long-term prognosis of patients with IPE and discussed the semiological and electroencephalography (EEG) data in terms of syndromic characteristics. MATERIAL AND METHODS This study included a group of consecutive patients with IPE who had been followed since 1990. Demographic and clinical variables were investigated. Patients were divided into 3 groups - A: Cases suitable for a single IPE (BECTS, PS and CEOP); B: cases with intermediate characteristics within IPEs; and C: cases with both IPE and IGE characteristics. Long-term data regarding the individual seizure types and EEG findings were re-evaluated. RESULTS A total of 61 patients were included in the study. Mean follow-up duration was 7.8 ± 4.50 years. The mean age at onset of seizures was 7.7 years. There were 40 patients in group A 40, 14 in group B, and 7 in group C. Seizure and EEG characteristics were also explored independently from the syndromic approach. Incidence of autonomic seizures is considerably high at 2-5 years and incidence of oromotor seizures is high at age 9-11 years. The EEG is most abnormal at 6-8 years. The vast majority (86%) of epileptic activity (EA) with parietooccipital is present at 2-5 years, whereas EA with fronto-temporal or multiple sites become more abundant between ages 6 and 11. CONCLUSIONS Results of the present study provide support for the age-related characteristics of the seizures and EEGs in IPE syndromes. Acknowledgement of those phenomena may improve the management of IPEs and give a better estimate of the future consequences.

Integrating EEG and fMRI in epilepsy.

PubMed

Formaggio, Emanuela; Storti, Silvia Francesca; Bertoldo, Alessandra; Manganotti, Paolo; Fiaschi, Antonio; Toffolo, Gianna Maria

2011-02-14

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies enables to non-invasively investigate human brain function and to find the direct correlation of these two important measures of brain activity. Presurgical evaluation of patients with epilepsy is one of the areas where EEG and fMRI integration has considerable clinical relevance for localizing the brain regions generating interictal epileptiform activity. The conventional analysis of EEG-fMRI data is based on the visual identification of the interictal epileptiform discharges (IEDs) on scalp EEG. The convolution of these EEG events, represented as stick functions, with a model of the fMRI response, i.e. the hemodynamic response function, provides the regressor for general linear model (GLM) analysis of fMRI data. However, the conventional analysis is not automatic and suffers of some subjectivity in IEDs classification. Here, we present an easy-to-use and automatic approach for combined EEG-fMRI analysis able to improve IEDs identification based on Independent Component Analysis and wavelet analysis. EEG signal due to IED is reconstructed and its wavelet power is used as a regressor in GLM. The method was validated on simulated data and then applied on real data set consisting of 2 normal subjects and 5 patients with partial epilepsy. In all continuous EEG-fMRI recording sessions a good quality EEG was obtained allowing the detection of spontaneous IEDs and the analysis of the related BOLD activation. The main clinical finding in EEG-fMRI studies of patients with partial epilepsy is that focal interictal slow-wave activity was invariably associated with increased focal BOLD responses in a spatially related brain area. Our study extends current knowledge on epileptic foci localization and confirms previous reports suggesting that BOLD activation associated with slow activity might have a role in localizing the epileptogenic region even in the absence of clear interictal spikes. Copyright © 2010 Elsevier Inc. All rights reserved.

Treatment of depression in patients with epilepsy.

PubMed

Noe, Katherine H; Locke, Dona E C; Sirven, Joseph I

2011-08-01

In this article, we review the current best evidence for the treatment of depression in patients with epilepsy. Depression is a common epilepsy comorbidity, but it is often unrecognized. The most important step in appropriately managing mood disorders in this population is making the diagnosis. Clinical vigilance and routine use of a validated screening tool can improve detection and quality of care. As is increasingly the case for the general population, persons with epilepsy are often interested in exploring alternative therapies for chronic conditions, including depression. Unfortunately, the benefit of complementary and alternative therapies for depression currently is largely unproven for persons with a seizure history, although an early study of exercise for mild depression has shown some benefit. Concerns about drug interactions, side effects, and expense may be barriers to the prescription of antidepressant medications for people requiring chronic antiepileptic drug (AED) therapy. For this reason, use of an AED with mood-stabilizing properties has appeal and may be appropriate for selected individuals with mild depressive symptoms. Undue fear of lowering seizure threshold should not preclude the prescription of an antidepressant medication, as the perceived risks are often overestimated and rarely outweigh the risk of leaving depression untreated. At present, the best evidence for efficacy and safety support the use of citalopram, sertraline, or mirtazapine as initial pharmacotherapy, whereas bupropion should be avoided. Start low, go slow, and use the lowest effective dose. Cognitive behavioral therapy is a valuable adjunct to antidepressant therapy in this population. For people with refractory partial epilepsy and refractory depression, vagus nerve stimulation has some appeal, in that it may be beneficial for both conditions, but the efficacy of vagus nerve stimulation in improving mood in patients with epilepsy remains unclear.

De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy.

PubMed

de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah; Møller, Rikke S; Velinov, Milen; Dolzhanskaya, Natalia; Marsh, Eric; Helbig, Ingo; Devinsky, Orrin; Tang, Sha; Mefford, Heather C; Myers, Candace T; van Paesschen, Wim; Striano, Pasquale; van Gassen, Koen; van Kempen, Marjan; de Kovel, Carolien G F; Piard, Juliette; Minassian, Berge A; Nezarati, Marjan M; Pessoa, André; Jacquette, Aurelia; Maher, Bridget; Balestrini, Simona; Sisodiya, Sanjay; Warde, Marie Therese Abi; De St Martin, Anne; Chelly, Jamel; van 't Slot, Ruben; Van Maldergem, Lionel; Brilstra, Eva H; Koeleman, Bobby P C

2016-12-01

Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy. 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/.

[Linkage analysis in an extended multigenerational family segregating for idiopathic epilepsy].

PubMed

Palacio, L G; Sánchez, J L; Jiménez, M E; Rivera-Valencia, D; Jiménez-Ramírez, I; Arcos, O M

Linkage analyses enable us to identify the loci that bestow susceptibility to certain diseases which are assumed to have a genetic aetiology by determining the cosegregation of alleles of specific markers within families. The aim of this study was to determine whether there is generalised idiopathic epilepsy (GIE) susceptibility in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions within an extended multigenerational family belonging to the Paisa community in Antioquia, a genetic isolate located in Colombia segregating for GIE with a strong capacity for detecting linkage. A family with a number of individuals affected by idiopathic epilepsy who visited the Instituto Neurológico de Antioquia was selected for study. An affected individual was required to have been diagnosed by a neurologist as suffering from non-myoclonic idiopathic epilepsy or partial idiopathic epilepsy. All patients suspected of suffering from idiopathic epilepsy were submitted to video monitoring in order to characterise the seizures electroencephalographically. Of the 106 individuals in this family that were included in the family tree, 76 were genotyped, 15 of whom were affected by generalised clonic tonic seizures and six were considered to be possibly affected. Results of the lod score were significantly negative for all the markers in relation to each model that was considered. The possibility of the genes located in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions being responsible for the familial aggregation of GIE in this family was ruled out, which is in accordance with claims made in previous studies conducted on other families.

Epilepsy Characteristics and Clinical Outcome in Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS).

PubMed

Lee, Ha Neul; Eom, Soyong; Kim, Se Hoon; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Heung Dong; Lee, Young-Mock

2016-11-01

Epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are heterogeneous with no pathognomonic features. We reviewed epilepsy characteristics and clinical outcome exclusively in a pediatric population. Twenty-two children and adolescents (13 males) with confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes due to mitochondrial DNA A3243G mutation and epilepsy were recruited. Clinical data including seizure semiology, treatment response, neuroimaging findings, and electroencephalography were analyzed. We also examined the effect of the age at seizure onset and initial symptoms on the clinical variables. Seizure semiology and electroencephalography abnormalities showed no syndrome-specific findings. Focal seizures occurred in 21 of 22 subjects (95.5%), whereas generalized seizures developed in seven of 22 subjects (31.8%). Twenty of 22 subjects (90.9%) achieved partial to complete reduction of clinical seizures for more than one year with a combination of more than two antiepileptic drugs. The subgroup with earlier seizure onset presented significantly earlier and showed significantly higher rates of drug-resistant epilepsy compared with the late onset group, although there were no significant differences in the initial symptoms. The subjects with severe epileptic conditions tended to have more severe clinical dysfunction and more severe organ involvement. Both focal and generalized seizures occurred in patients with MELAS. Epilepsy in this population is drug resistant, but a certain degree of clinical seizure reduction was achievable with antiepileptic drugs, with more favorable outcomes than historically expected. Close observation and active epilepsy treatment of individuals with MELAS episodes and earlier seizure onset might improve the prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

A neuropsychological assessment, using computerized battery tests (CANTAB), in children with benign rolandic epilepsy before AED therapy.

PubMed

Vinţan, M A; Palade, S; Cristea, A; Benga, I; Muresanu, D F

2012-02-22

Benign rolandic epilepsy (BRE) is a form of partial idiopathic epilepsy according to the International League Against Epilepsy (ILAE) syndromes classification (1989). Recent studies have identified cases of BRE that do not meet the initial definition of 'benign'; these included reports of cases with specific cognitive deficits. It is still a matter of debate, whether these deficits are due to epilepsy per se, to treatment or other associated factors. The aim of this study was to evaluate if BRE children have cognitive deficits at the onset of their seizures, prior to their participation in any anti-epileptic drug therapy (AED). We performed a neuropsychological assessment of 18 BRE children compared with a corresponding age-matched control group. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjects were at their first neurological evaluation, before any AED therapy. We assessed: visual memory, induction and executive functions. In our group, the BRE children performed comparably with the control children for the induction and executive functions. Substantial differences were identified for the visual memory subtests: PRM percent correct (t = -2.58, p = 0.01) and SRM percent correct (t = -2.73, p = 0.01). Age of seizure onset had a negative impact on the visual memory subtest performances (PRM mean correct latency). We found significant correlations between the different CANTAB subtests results and characteristics of the centrotemporal spikes (CTS). Our results are consistent with the findings of other similar studies. This form of epilepsy is associated with subtle neuropsychological deficits, present at seizure onset. Neuropsychological deficits identified, suggest a more diffuse brain involvement in the epileptiform process.

Epilepsy following cortical injury: Cellular and molecular mechanisms as targets for potential prophylaxis

PubMed Central

Prince, David A.; Parada, Isabel; Scalise, Karina; Graber, Kevin; Shen, Fran

2009-01-01

Summary The sequelae of traumatic brain injury, including posttraumatic epilepsy, represent a major societal problem. Significant resources are required to develop a better understanding of the underlying pathophysiologic mechanisms as targets for potential prophylactic therapies. Posttraumatic epilepsy undoubtedly involves numerous pathogenic factors that develop more or less in parallel. We have highlighted two potential “prime movers”: disinhibition and development of new functional excitatory connectivity, which occur in a number of animal models and some forms of epilepsy in humans. Previous experiments have shown that tetrodotoxin (TTX) applied to injured cortex during a critical period early after lesion placement can prevent epileptogenesis in the partial cortical (“undercut”) model of posttraumatic epilepsy. Here we show that such treatment markedly attenuates histologic indices of axonal and terminal sprouting and presumably associated aberrant excitatory connectivity. A second finding in the undercut model is a decrease in spontaneous inhibitory events. Current experiments show that this is accompanied by regressive alterations in fast-spiking γ-aminobutyric acid (GABA)ergic interneurons, including shrinkage of dendrites, marked decreases in axonal length, structural changes in inhibitory boutons, and loss of inhibitory synapses on pyramidal cells. Other data support the hypothesis that these anatomic abnormalities may result from loss of trophic support normally provided to interneurons by brain-derived neurotrophic factor (BDNF). Approaches that prevent these two pathophysiologic mechanisms may offer avenues for prophylaxis for posttraumatic epilepsy. However, major issues such as the role of these processes in functional recovery from injury and the timing of the critical period(s) for application of potential therapies in humans are critical and need to be resolved. PMID:19187292

Clinical utility of flumazenil-PET versus [18F]fluorodeoxyglucose-PET and MRI in refractory partial epilepsy. A prospective study in 100 patients.

PubMed

Ryvlin, P; Bouvard, S; Le Bars, D; De Lamérie, G; Grégoire, M C; Kahane, P; Froment, J C; Mauguière, F

1998-11-01

We assessed the clinical utility of [11C]flumazenil-PET (FMZ-PET) prospectively in 100 epileptic patients undergoing a pre-surgical evaluation, and defined the specific contribution of this neuro-imaging technique with respect to those of MRI and [18F]fluorodeoxyglucose-PET (FDG-PET). All patients benefited from a long term video-EEG monitoring, whereas an intracranial EEG investigation was performed in 40 cases. Most of our patients (73%) demonstrated a FMZ-PET abnormality; this hit rate was significantly higher in temporal lobe epilepsy (94%) than in other types of epilepsy (50%) (P < 0.001). Most FMZ-PET findings coexisted with a MRI abnormality (81%), including hippocampal atrophy (35%) and focal hypometabolism on FDG-PET (89%). The area of decreased FMZ binding was often smaller than that of glucose hypometabolism (48%) or larger than that of the MRI abnormality (28%). FMZ-PET did not prove superior to FDG-PET in assessing the extent of the ictal onset zone, as defined by intracranial EEG recordings. However, it provided useful data which were complementary to those of MRI and FDG-PET in three situations: (i) in temporal lobe epilepsy associated with MRI signs of hippocampal sclerosis, FMZ-PET abnormalities delineated the site of seizure onset precisely, whenever they were coextensive with FDG-PET abnormalities; (ii) in bi-temporal epilepsy, FMZ-PET helped to confirm the bilateral origin of seizures by showing a specific pattern of decreased FMZ binding in both temporal lobes in 33% of cases; (iii) in patients with a unilateral cryptogenic frontal lobe epilepsy, FMZ-PET provided further evidence of the side and site of seizure onset in 55% of cases. Thus, FMZ-PET deserves to be included in the pre-surgical evaluation of these specific categories of epileptic patients, representing approximately half of the population considered for epilepsy surgery.

Vigabatrin and lamotrigine in refractory epilepsy.

PubMed Central

Stolarek, I; Blacklaw, J; Forrest, G; Brodie, M J

1994-01-01

Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain. Vigabatrin (VIG) decreases the breakdown of the inhibitory neurotransmitter gamma-aminobutyric acid, whereas lamotrigine (LTG) reduces presynaptic excitatory amino acid release. 22 patients with refractory epilepsy, treated with an anticonvulsant regimen containing VIG, entered a balanced, double blind, placebo controlled, crossover trial of additional LTG. Treatment periods of 12 weeks (25 mg, 50 mg, 100 mg LTG twice daily for four weeks at each dose, and matched placebo) were followed by wash out intervals of four weeks. 14 of the 20 patients completing the study improved, resulting in a significant fall in seizure days and numbers. Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures. At the highest LTG dose (200 mg daily) there was a median fall of 37% in seizure count with nine (45%) patients reporting > 50% reduction. Three of these patients were seizure free during this month of treatment. Side effects were minimal throughout the study. Concentrations of other antiepileptic drugs, including those of carbamazepine 10,11-epoxide, were not modified by LTG. This study suggests a substantial efficacy for a regimen containing VIG and LTG. Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy. PMID:8057114

Déjà Experiences in Temporal Lobe Epilepsy

PubMed Central

Illman, Nathan A.; Butler, Chris R.; Souchay, Celine; Moulin, Chris J. A.

2012-01-01

Historically, déjà vu has been linked to seizure activity in temporal lobe epilepsy, and clinical reports suggest that many patients experience the phenomenon as a manifestation of simple partial seizures. We review studies on déjà vu in epilepsy with reference to recent advances in the understanding of déjà vu from a cognitive and neuropsychological standpoint. We propose a decoupled familiarity hypothesis, whereby déjà vu is produced by an erroneous feeling of familiarity which is not in keeping with current cognitive processing. Our hypothesis converges on a parahippocampal dysfunction as the locus of déjà vu experiences. However, several other temporal lobe structures feature in reports of déjà vu in epilepsy. We suggest that some of the inconsistency in the literature derives from a poor classification of the various types of déjà experiences. We propose déjà vu/déjà vécu as one way of understanding déjà experiences more fully. This distinction is based on current models of memory function, where déjà vu is caused by erroneous familiarity and déjà vécu by erroneous recollection. Priorities for future research and clinical issues are discussed. PMID:22957231

Déjà experiences in temporal lobe epilepsy.

PubMed

Illman, Nathan A; Butler, Chris R; Souchay, Celine; Moulin, Chris J A

2012-01-01

Historically, déjà vu has been linked to seizure activity in temporal lobe epilepsy, and clinical reports suggest that many patients experience the phenomenon as a manifestation of simple partial seizures. We review studies on déjà vu in epilepsy with reference to recent advances in the understanding of déjà vu from a cognitive and neuropsychological standpoint. We propose a decoupled familiarity hypothesis, whereby déjà vu is produced by an erroneous feeling of familiarity which is not in keeping with current cognitive processing. Our hypothesis converges on a parahippocampal dysfunction as the locus of déjà vu experiences. However, several other temporal lobe structures feature in reports of déjà vu in epilepsy. We suggest that some of the inconsistency in the literature derives from a poor classification of the various types of déjà experiences. We propose déjà vu/déjà vécu as one way of understanding déjà experiences more fully. This distinction is based on current models of memory function, where déjà vu is caused by erroneous familiarity and déjà vécu by erroneous recollection. Priorities for future research and clinical issues are discussed.

When should temporal-lobe epilepsy be treated surgically?

PubMed

Spencer, Susan S

2002-10-01

Our current knowledge of mesial-temporal-lobe epilepsy (MTLE) is extensive, yet still insufficient to draw final conclusions on the optimal approach to its therapy. MTLE has been well characterised and can usually be identified with noninvasive studies including scalp electroencephalography (EEG) and video monitoring with ictal recording, magnetic resonance imaging, single-photon-emission computed tomography, positron emission tomography, neuropsychological assessment, and historical and clinical data. Sometimes, invasive EEG is needed to confirm mesial-temporal-lobe seizure onset, which, combined with the underlying pathological abnormality (the substrate) of mesial temporal sclerosis (hippocampal neuronal loss and gliosis), defines MTLE. This disorder is the most common refractory partial epilepsy, and also the one most often treated surgically, because medical treatment fails in 75% of cases, and surgical treatment succeeds in a similar percentage. Despite the recent publication of the first randomised trial of surgical treatment for MTLE, questions remain about the neurological consequences of both medical and surgical treatment, the ultimate gains in quality of life parameters, and the precise predictors of success. Long-term follow-up and analyses of multiple factors in large groups of contemporary patient populations will be necessary to fully answer the question, "is temporal lobe epilepsy a surgical disease?" Right now it should be considered one in most cases.

Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target

PubMed Central

Galanopoulou, Aristea S.; Gorter, Jan A.; Cepeda, Carlos

2012-01-01

Summary The mTOR signaling pathway regulates cell growth, differentiation, proliferation and metabolism. Loss of function mutations in upstream regulators of mTOR have been highly associated with dysplasias, epilepsy and neurodevelopmental disorders. These include tuberous sclerosis, which is due to mutations in TSC1 or TSC2 genes, mutations in phosphatase and tensin homolog (PTEN) as in Cowden syndrome, polyhydramnios, megalencephaly, symptomatic epilepsy syndrome (PMSE) due to mutations in the STE20-related kinase adaptor alpha (STRADalpha), and neurofibromatosis type 1 attributed to neurofibromin 1 mutations. Inhibition of the mTOR pathway with rapamycin may prevent epilepsy and improve the underlying pathology in mouse models with disrupted mTOR signaling, due to PTEN or TSC mutations. However the timing and duration of its administration appear critical in defining the seizure and pathology-related outcomes. Rapamycin application in human cortical slices from patients with cortical dysplasias reduces the 4-aminopyridine induced oscillations. In the multiple-hit model of infantile spasms, pulse high dose rapamycin administration can reduce the cortical overactivation of the mTOR pathway, suppresses spasms and has disease-modifying effects by partially improving cognitive deficits. In post-status epilepticus models of temporal lobe epilepsy, rapamycin may ameliorate the development of epilepsy-related pathology and reduce the expression of spontaneous seizures, but its effects depend on the timing and duration of administration, and possibly the model used. The observed recurrence of seizures and epilepsy-related pathology after rapamycin discontinuation suggests the need for continuous administration to maintain the benefit. However, the use of pulse administration protocols may be useful in certain age-specific epilepsy syndromes, like infantile spasms, whereas repetitive pulse rapamycin protocols may suffice to sustain a long-term benefit in genetic disorders of the mTOR pathway. In summary, mTOR dysregulation has been implicated in several genetic and acquired forms of epileptogenesis. The use of mTOR inhibitors can reverse some of these epileptogenic processes although their effects depend upon the timing and dose of administration as well as the model used. PMID:22578218

Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy.

PubMed

Rubí, Sebastià; Costes, Nicolas; Heckemann, Rolf A; Bouvard, Sandrine; Hammers, Alexander; Martí Fuster, Berta; Ostrowsky, Karine; Montavont, Alexandra; Jung, Julien; Setoain, Xavier; Catenoix, Hélène; Hino, Keiko; Liger, François; Le Bars, Didier; Ryvlin, Philippe

2013-12-01

Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity. We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity. A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3-34%) and 100% (95% CI: 97-100%), respectively. AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis.

PubMed

Comper, Sandra Mara; Jardim, Anaclara Prada; Corso, Jeana Torres; Gaça, Larissa Botelho; Noffs, Maria Helena Silva; Lancellotti, Carmen Lúcia Penteado; Cavalheiro, Esper Abrão; Centeno, Ricardo Silva; Yacubian, Elza Márcia Targas

2017-10-01

The objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield. The hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36). There were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p=0.048). The groups with HS presented different memory performance - the right HS were worse in visual memory test [Complex Rey Figure, immediate (p=0.001) and delayed (p=0.009)], but better in one verbal task [RAVLT delayed (p=0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p=0.050) and Logical Memory and RAVLT delayed recalls (p=0.004 and p=0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p=0.006) and epilepsy duration (p=0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p<0.001). Cornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS. Copyright © 2017 Elsevier Inc. All rights reserved.

Does the concept of resilience contribute to understanding good quality of life in the context of epilepsy?

PubMed

Ring, Adele; Jacoby, Ann; Baker, Gus A; Marson, Anthony; Whitehead, Margaret M

2016-03-01

A significant body of research highlights negative impacts of epilepsy for individual quality of life (QOL). Poor seizure control is frequently associated with reporting of poor QOL and good seizure control with good QOL; however, this is not a universal finding. Evidence suggests that some people enjoy good QOL despite ongoing seizures while others report poor QOL despite good seizure control. Understanding the factors that influence QOL for people with epilepsy and the processes via which such factors exert their influence is central to the development of interventions to support people with epilepsy to experience the best possible QOL. We present findings of a qualitative investigation exploring influences and processes on QOL for people with epilepsy. We describe the clinical, psychological, and social factors contributing to QOL. In particular, we focus on the value of the concept of resilience for understanding quality of life in epilepsy. Based on our analysis, we propose a model of resilience wherein four key component sets of factors interact to determine QOL. This model reflects the fluid nature of resilience that, we suggest, is subject to change based on shifts within the individual components and the interactions between them. The model offers a representation of the complex influences that act and interact to either mitigate or further compound the negative impacts of epilepsy on individual QOL. Copyright © 2016 Elsevier Inc. All rights reserved.

Delivery of epilepsy care to adults with intellectual and developmental disabilities

PubMed Central

Asato, Miya; Camfield, Peter; Geller, Eric; Kanner, Andres M.; Keller, Seth; Kerr, Michael; Kossoff, Eric H.; Lau, Heather; Kothare, Sanjeev; Singh, Baldev K.; Wirrell, Elaine

2015-01-01

Epilepsy is common in people with intellectual and developmental disabilities (IDD). In adulthood, patients with IDD and epilepsy (IDD-E) have neurologic, psychiatric, medical, and social challenges compounded by fragmented and limited care. With increasing neurologic disability, there is a higher frequency of epilepsy, especially symptomatic generalized and treatment-resistant epilepsies. The causes of IDD-E are increasingly recognized to be genetic based on chromosomal microarray analysis to identify copy number variants, gene panels (epilepsy, autism spectrum disorder, intellectual disability), and whole-exome sequencing. A specific genetic diagnosis may guide care by pointing to comorbid disorders and best therapy. Therapy to control seizures should be individualized, with drug selection based on seizure types, epilepsy syndrome, concomitant medications, and comorbid disorders. There are limited comparative antiepileptic drug data in the IDD-E population. Vagus nerve and responsive neural stimulation therapies and resective surgery should be considered. Among the many comorbid disorders that affect patients with IDD-E, psychiatric and sleep disorders are common but often unrecognized and typically not treated. Transition from holistic and coordinated pediatric to adult care is often a vulnerable period. Communication among adult health care providers is complex but essential to ensure best care when these patients are seen in outpatient, emergency room, and inpatient settings. We propose specific recommendations for minimum care standards for people with IDD-E. PMID:26423430

Stimulation of the nervous system for the management of seizures: current and future developments.

PubMed

Murphy, Jerome V; Patil, Arunangelo

2003-01-01

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Seizures in Fragile X Syndrome: Characteristics and Comorbid Diagnoses

ERIC Educational Resources Information Center

Berry-Kravis, Elizabeth; Raspa, Melissa; Loggin-Hester, Lisa; Bishop, Ellen; Holiday, David; Bailey, Donald B., Jr.

2010-01-01

A national survey of caregivers of individuals with fragile X syndrome addressed characteristics of epilepsy and co-occurring conditions. Of the 1,394 individuals (1,090 males and 304 females) with the full mutation, 14% of males and 6% of females reported seizures. Seizures were more often partial, began between ages 4 and 10 years, and were…

Epilepsy: creative sparks.

PubMed

Thomas, Rhys H; Mullins, Jane M; Waddington, Tracey; Nugent, Kane; Smith, Phil E M

2010-08-01

An epilepsy diagnosis is very verbal, relying on witness history, personal narrative and analysis of how people describe the experience. Occasionally however, non-verbal descriptions of seizures allow us to gain a fuller understanding of this complex disorder. Artists are often inspired by personal experience, so it should be no surprise to find people depicting images of ill health, both their own and people they have observed. Furthermore, an ailment or affliction may influence an artist's portfolio over their lifetime, such as de Kooning's Alzheimer's disease and Monet's glaucoma. Epilepsy (in contrast with cerebrovascular or neurodegenerative disease) may present not just with a loss of function but with unusual super-added experiences such as déjà vu, ecstatic auras or hallucinations. Here we describe some artists who were thought to have had epilepsy, and the way in which their seizures influenced their art. It appears that for some, they have succeeded despite, rather than because of, their epilepsy and that rather than be inspired by their symptoms they were ashamed of them. If there is a common theme, it is in the unwanted psychological harm of some seizures provoking dark, frustrated imagery.

Complement system biomarkers in epilepsy.

PubMed

Kopczynska, Maja; Zelek, Wioleta M; Vespa, Simone; Touchard, Samuel; Wardle, Mark; Loveless, Samantha; Thomas, Rhys H; Hamandi, Khalid; Morgan, B Paul

2018-05-24

To explore whether complement dysregulation occurs in a routinely recruited clinical cohort of epilepsy patients, and whether complement biomarkers have potential to be used as markers of disease severity and seizure control. Plasma samples from 157 epilepsy cases (106 with focal seizures, 46 generalised seizures, 5 unclassified) and 54 controls were analysed. Concentrations of 10 complement analytes (C1q, C3, C4, factor B [FB], terminal complement complex [TCC], iC3b, factor H [FH], Clusterin [Clu], Properdin, C1 Inhibitor [C1Inh] plus C-reactive protein [CRP]) were measured using enzyme linked immunosorbent assay (ELISA). Univariate and multivariate statistical analysis were used to test whether combinations of complement analytes were predictive of epilepsy diagnoses and seizure occurrence. Correlation between number and type of anti-epileptic drugs (AED) and complement analytes was also performed. We found: CONCLUSION: This study adds to evidence implicating complement in pathogenesis of epilepsy and may allow the development of better therapeutics and prognostic markers in the future. Replication in a larger sample set is needed to validate the findings of the study. Copyright © 2018. Published by Elsevier Ltd.

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.

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

PubMed

Régis, J; Bartolomei, F; de Toffol, B; Genton, P; Kobayashi, T; Mori, Y; Takakura, K; Hori, T; Inoue, H; Schröttner, O; Pendl, G; Wolf, A; Arita, K; Chauvel, P

2000-12-01

Drug-resistant epilepsy associated with hypothalamic hamartomas (HHs) can be cured by microsurgical resection of the lesions. Morbidity and mortality rates for microsurgery in this area are significant. Gamma knife surgery (GKS) is less invasive and seems to be well adapted for this indication. To evaluate the safety and efficacy of GKS to treat this uncommon pathological condition, we organized a multicenter retrospective study. Ten patients were treated in seven different centers. The follow-up periods were more than 12 months for eight patients, with a median follow-up period of 28 months (mean, 35 mo; range, 12-71 mo). All patients had severe drug-resistant epilepsy, including frequent gelastic and generalized tonic or tonicoclonic attacks. The median age was 13.5 years (range, 1-32 yr; mean, 14 yr) at the time of GKS. Three patients experienced precocious puberty. All patients had sessile HHs. The median marginal dose was 15.25 Gy (range, 12-20 Gy). Two patients were treated two times (at 19 and 49 mo) because of insufficient efficacy. All patients exhibited improvement. Four patients were seizure-free, one experienced rare nocturnal seizures, one experienced some rare partial seizures but no more generalized attacks, and two exhibited only improvement, with reductions in the frequency of seizures but persistence of some rare generalized seizures. Two patients, now seizure-free, were considered to exhibit insufficient improvement after the first GKS procedure and were treated a second time. A clear correlation between efficacy and dose was observed in this series. The marginal dose was more than 17 Gy for all patients in the successful group and less than 13 Gy for all patients in the "improved" group. No side effects were reported, except for poikilothermia in one patient. Behavior was clearly improved for two patients (with only slight improvements in their epilepsy). Complete coverage of the HHs did not seem to be mandatory, because the dosimetry spared a significant part of the lesions for two patients in the successful group. We report the first series demonstrating that GKS can be a safe and effective treatment for epilepsy related to HHs. We advocate marginal doses greater than or equal to 17 Gy and partial dose-planning when necessary, for avoidance of critical surrounding structures.

Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings.

PubMed

Pedreira, C; Vaudano, A E; Thornton, R C; Chaudhary, U J; Vulliemoz, S; Laufs, H; Rodionov, R; Carmichael, D W; Lhatoo, S D; Guye, M; Quian Quiroga, R; Lemieux, L

2014-10-01

Scalp EEG recordings and the classification of interictal epileptiform discharges (IED) in patients with epilepsy provide valuable information about the epileptogenic network, particularly by defining the boundaries of the "irritative zone" (IZ), and hence are helpful during pre-surgical evaluation of patients with severe refractory epilepsies. The current detection and classification of epileptiform signals essentially rely on expert observers. This is a very time-consuming procedure, which also leads to inter-observer variability. Here, we propose a novel approach to automatically classify epileptic activity and show how this method provides critical and reliable information related to the IZ localization beyond the one provided by previous approaches. We applied Wave_clus, an automatic spike sorting algorithm, for the classification of IED visually identified from pre-surgical simultaneous Electroencephalogram-functional Magnetic Resonance Imagining (EEG-fMRI) recordings in 8 patients affected by refractory partial epilepsy candidate for surgery. For each patient, two fMRI analyses were performed: one based on the visual classification and one based on the algorithmic sorting. This novel approach successfully identified a total of 29 IED classes (compared to 26 for visual identification). The general concordance between methods was good, providing a full match of EEG patterns in 2 cases, additional EEG information in 2 other cases and, in general, covering EEG patterns of the same areas as expert classification in 7 of the 8 cases. Most notably, evaluation of the method with EEG-fMRI data analysis showed hemodynamic maps related to the majority of IED classes representing improved performance than the visual IED classification-based analysis (72% versus 50%). Furthermore, the IED-related BOLD changes revealed by using the algorithm were localized within the presumed IZ for a larger number of IED classes (9) in a greater number of patients than the expert classification (7 and 5, respectively). In contrast, in only one case presented the new algorithm resulted in fewer classes and activation areas. We propose that the use of automated spike sorting algorithms to classify IED provides an efficient tool for mapping IED-related fMRI changes and increases the EEG-fMRI clinical value for the pre-surgical assessment of patients with severe epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Five pediatric cases of ictal fear with variable outcomes.

PubMed

Akiyama, Mari; Kobayashi, Katsuhiro; Inoue, Takushi; Akiyama, Tomoyuki; Yoshinaga, Harumi

2014-10-01

Ictal fear is an uncommon condition in which fear manifests as the main feature of epileptic seizures. The literature has suggested that ictal fear is generally associated with poor seizure outcomes. We wanted to clarify the variability in seizure outcome of children with ictal fear. We identified five pediatric patients with ictal fear who were followed up on at Okayama University Hospital between January 2003 and December 2012. We retrospectively reviewed their clinical records and EEG findings. The onset age of epilepsy ranged from 8 months to 9 years and 10 months. The common ictal symptoms were sudden fright, clinging to someone nearby, and subsequent impairment of consciousness, which were often accompanied by complex visual hallucinations and psychosis-like complaints. Ictal fear, in four patients, was perceived as a nonepileptic disorder by their parents. Ictal electroencephalograms (EEG) of ictal fear were obtained in all patients. Three showed frontal onset, while the other two showed centrotemporal or occipital onsets. Two patients were seizure free at last follow-up, while seizures persisted in the other three. A patient with seizure onset during infancy had a favorable outcome, which was considered to be compatible with benign partial epilepsy with affective symptoms. Ictal fear is not always associated with a symptomatic cause or a poor seizure outcome. It is quite important to make a correct diagnosis of ictal fear as early as possible to optimize treatment. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. 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

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008

PubMed Central

Gabriël, Sarah; Benitez-Ortiz, Washington; Saegerman, Claude; Dorny, Pierre; Berkvens, Dirk; Abatih, Emmanuel Nji

2015-01-01

Background Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex. Methodology Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC. Principal findings Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC95%; 0.2%–1.8%) and by 5.12% (IC95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC. Conclusion/Significance Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due to NCC from epilepsies due to other causes. Field studies are needed to evaluate the true prevalence of cysticercosis in humans and pigs in different zones of the country in order to better implement and manage prevention and/or control campaigns. PMID:26580210

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008.

PubMed

Ron-Garrido, Lenin; Coral-Almeida, Marco; Gabriël, Sarah; Benitez-Ortiz, Washington; Saegerman, Claude; Dorny, Pierre; Berkvens, Dirk; Abatih, Emmanuel Nji

2015-11-01

Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex. Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC. Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC95%; 0.2%-1.8%) and by 5.12% (IC95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC. Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due to NCC from epilepsies due to other causes. Field studies are needed to evaluate the true prevalence of cysticercosis in humans and pigs in different zones of the country in order to better implement and manage prevention and/or control campaigns.

The Managing Epilepsy Well Network:: Advancing Epilepsy Self-Management.

PubMed

Sajatovic, Martha; Jobst, Barbara C; Shegog, Ross; Bamps, Yvan A; Begley, Charles E; Fraser, Robert T; Johnson, Erica K; Pandey, Dilip K; Quarells, Rakale C; Scal, Peter; Spruill, Tanya M; Thompson, Nancy J; Kobau, Rosemarie

2017-03-01

Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two study reports, seven book chapters, and 62 presentations and posters. To date, two programs have been adopted and disseminated by the national Epilepsy Foundation, state Epilepsy Foundation affiliates, and other stakeholders. Recent expansion of the MEW Network membership will help to extend future reach and public health impact. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

Role of Altered mGluR Activity in Cognitive Impairments in TSC: Implications for a Novel Method of Treatment

DTIC Science & Technology

2013-04-01

epilepsy, autism , anxiety and mood disorders. Fragile X syndrome (FXS), another form of inherited mental retardation and autism , shares many of the...therapeutic intervention for several of the deficits observed in TSC. 15. SUBJECT TERMS autism , Tuberous Sclerosis Complex, Fragile X Syndrome...clinical features being mental retardation, epilepsy, autism , anxiety and mood disorders (Prather & de Vries, 2004). Fragile X syndrome (FXS

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

PubMed

Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

2015-06-01

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

From nocturnal frontal lobe epilepsy to Sleep-Related Hypermotor Epilepsy: A 35-year diagnostic challenge.

PubMed

Tinuper, Paolo; Bisulli, Francesca

2017-01-01

Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy with seizures arising mainly during sleep and characterized by complex, often bizarre, motor behavior or sustained dystonic posturing. First described in 1981, it was initially considered a motor disorder of sleep and was named nocturnal paroxysmal dystonia (NPD). The unusual seizure semiology, onset during sleep, and often uninformative scalp EEG and brain MRI make it difficult to distinguish NPD attacks from other non-epileptic nocturnal paroxysmal events, namely parasomnias. The long-debated epileptic origin of the condition was finally demonstrated in 1990 and the term NFLE introduced. Even though many aspects of parasomnias and NFLE have been clarified in the last two decades, the differential diagnosis remains a challenge for clinicians. To address controversial issues and define the diagnostic criteria for NFLE, a Consensus Conference was held in Bologna, Italy in 2014. Major points of agreement emerged on: (i) the relationship of the seizures with sleep and not with the circadian pattern of seizure occurrence; (ii) the possible extrafrontal origin of hypermotor seizures, without substantial differences in seizure semiology. In the wake of the Consensus, the syndrome was renamed Sleep-Related Hypermotor Epilepsy (SHE). Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis.

PubMed

Borusiak, Peter; Bettendorf, Ulrich; Wiegand, Gert; Bast, Thomas; Kluger, Gerhard; Philippi, Heike; Münstermann, Dieter; Bien, Christian G

2016-07-01

There is increasing awareness of neuronal autoantibodies and their impact on the pathogenesis of epilepsy. We investigated children with focal epilepsy in order to provide an estimate of autoantibody frequency within a pediatric population without prima facie evidence of encephalitis using a broad panel of autoantibodies. This was done to assess the specificity of antibodies and to see whether antibodies might be of modifying influence on the course of focal epilepsies. We searched for autoantibodies in 124 patients with focal epilepsy (1-18 years; mean 10; 6 years). Sera were tested using a broad panel of surface and intracellular antigens. We found autoantibodies in 5/124 patients (4%): high-positive GAD65 antibodies (n = 1), low-positive GAD65 antibodies (N = 1), VGKC complex antibodies not reactive with LGI1 or CASPR2 (n = 3). We did not find any distinctive features distinguishing antibody positive patients from those without antibodies. The antibodies found in this cohort are probably neither disease-specific nor pathogenic. This has been suggested before for these antigenic targets. Moreover, they do not seem to modify disease severity in the antibody-positive epilepsy patients. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Anxiety and depression in people with epilepsy: The contribution of metacognitive beliefs.

PubMed

Fisher, Peter L; Noble, Adam J

2017-08-01

Anxiety and depressive disorders frequently occur in people with epilepsy (PWE). An information processing model of psychopathology, the Self-Regulatory Executive Function (S-REF) model specifies that maladaptive metacognitive beliefs and processes play a fundamental role in the development and maintenance of anxiety and depression. This study explored whether metacognitive beliefs would explain additional variance in anxiety and depression after accounting for demographics, physical and/or psychiatric illnesses, epilepsy characteristics and medication issues. The mediational relationships between metacognitive beliefs, worry and anxiety and depression, predicted by the metacognitive model were also explored, METHODS: Three hundred and forty-nine PWE participated in an online survey and completed self-report questionnaires measuring anxiety, depression, metacognitive beliefs and worry. Participants also provided information on epilepsy characteristics, demographics, comorbid physical and/or psychiatric illnesses, number of, and perceived side effects of, anti-epileptic medication. Regression analysis showed that metacognitive beliefs were associated with symptoms of anxiety, depression, and explained additional variance in these outcomes after accounting for the control variables. Furthermore, the fundamental tenet of the metacognitive model was supported; the relationship between negative metacognitive beliefs about uncontrollability and danger of worry and anxious and depressive symptoms was partially mediated by worry. This is the first study to demonstrate that metacognitive beliefs and processes contribute to anxiety and depression beyond variables often associated with emotional distress in PWE. Further research is required to test if modification of metacognitive beliefs and processes using metacognitive therapy would effectively alleviate anxiety and depression in PWE. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Assessment of Time and Frequency Domain Parameters of Heart Rate Variability and Interictal Cardiac Rhythm Abnormalities in Drug-naïve Patients with Idiopathic Generalized Epilepsy.

PubMed

Kilinc, Ozden; Cincin, Altug; Pehlivan, Aslihan; Midi, Ipek; Kepez, Alper; Agan, Kadriye

2016-06-01

Epilepsy is a disease known to occur with autonomous phenomenons. Earlier studies indicate decreased heart rate variability (HRV) during ictal and interictal periods among epilepsy patients. In this study, we aim to investigate cardiac rhythm abnormalities and HRV during interictal period between drug-naïve patients with idiopathic generalized epilepsy (IGE) and healthy control group. Twenty-six patients with IGE and 26 healthy individuals included in the study. In order to eliminate any structural cardiac pathology, transthoracic echocardiography was performed in all subjects and time and frequency domain parameters of HRV were evaluated after 24-hour rhythm holter monitoring. Between two groups, no significant difference was detected in terms of mean heart rate and maximum duration between the start of the Q waves and the end of the T waves (QT intervals). In the time domain analysis of HRV, no statically significant difference was detected for standard deviation of all R - R intervals and root-mean-square of successive differences between patient and control group (p = 0,070 and p = 0,104 respectively). In the frequency domain analysis of HRV, patients tended to display lower total power and very low frequency power than did healthy subjects, but the differences were not statistically significant. Our results suggest that there is no major effect of the epilepsy on HRV in patients with IGE. It should be emphasized that, in this study, HRV was evaluated only in patients with IGE and that the results are not proper to be generalized for patients with partial seizures.

Use of anti-epileptic drugs in a tertiary care hospital of Eastern India with emphasis on epilepsy due to neurocysticercosis.

PubMed

Sil, Amrita; Das, Kamalesh; Das, Nilay K; Chakraborty, Dibyendu; Mazumdar, Goutameswar; Tripathi, Santanu K

2012-01-01

Epilepsy is a chronic disease and neurocysticercosis is an important cause of secondary seizures. Its therapy is modified by a number of parameters and thus the pattern of anti-epileptic drugs used varies in different clinical settings. It was our objective to evaluate clinico-demographic and treatment profile of epilepsy patients attending neurology outpatient department, efficacy and side-effect profile of anti-epileptic drugs with special emphasis on epilepsy resulting from neurocysticercosis. This was a cross-sectional descriptive study of epilepsy patients over four months in neurology outpatient department. Clinico-biological data were obtained by interrogating patients and from recorded data using standard case-report form. 79 patients were studied with 54.43% having primary etiology, 40.51% having seizures secondary to neurocysticercosis. 81% had generalized tonic-clonic seizure, 17.7% partial and 1.3% myoclonic seizures. Phenytoin (86.08%), valproate (30.38%), clobazam (26.58%) and carbamazepine (10.13%) were used either alone or in combination, with no use of anthelmintics even in cases of neurocysticercosis. Control of seizure was obtained in 79.7% with significant decrease in seizure frequency from 2.92 to 0.51 (P < 0.0001). Weight loss, nausea, decreased appetite, increased sleep, drowsiness, tremors were found to be significantly associated (P < 0.05) with phenytoin use. Phenytoin is the primary antiepileptic in spite of its side effects; though addition of other anti-epileptic drugs (valproate, clobazam) was required for better seizure control. Cases of neurocysticercosis respond to anti-epileptic drugs without addition of anthelmintics. Side effects observed were mostly neurological in nature.

Concerns regarding lamotrigine and breast-feeding.

PubMed

Liporace, Joyce; Kao, Amy; D'Abreu, Anelyssa

2004-02-01

Many women with epilepsy who are planning a pregnancy are treated with lamotrigine (LTG), resulting in greater fetal exposure to the drug. Current care guidelines suggest that mothers with epilepsy breast-feed their children. These recommendations are made without regard to how nursing newborns metabolize medication. Lamotrigine is extensively metabolized by glucuronidation, which is immature in neonates and may lead to accumulation of medication. This article reports LTG levels in full-term nursing newborns born to mothers with epilepsy on lamotrigine monotherapy. Serum LTG levels were obtained in nursing mothers and their neonates on Day 10 of life. Maternal LTG clearance during pregnancy and postpartum was determined and correlated with levels. Four mothers with partial epilepsy on LTG monotherapy were evaluated. Serum LTG levels in nursing newborns ranged from <1.0 to 2.0 microg/mL on Day 10 of life. Three babies had LTG levels >1.0 microg/mL. After excluding one child with an undetectable level, the LTG levels in newborns were on average 30% (range 20-43%) of the maternal drug level. No decline was noted in two children with repeat levels at 2 months. Serum concentrations of LTG in breast-fed children were higher than expected, in some cases reaching "therapeutic" ranges. These high levels may be explained by poor neonatal drug elimination due to inefficient glucuronidation. Our observation that not all newborns had a high LTG level suggests considerable genetic variability in metabolism. Our limited data suggest monitoring blood levels in nursing children and the need for individual counseling for women with epilepsy regarding breast-feeding.

Epilepsy: Transition from pediatric to adult care. Recommendations of the Ontario epilepsy implementation task force.

PubMed

Andrade, Danielle M; Bassett, Anne S; Bercovici, Eduard; Borlot, Felippe; Bui, Esther; Camfield, Peter; Clozza, Guida Quaglia; Cohen, Eyal; Gofine, Timothy; Graves, Lisa; Greenaway, Jon; Guttman, Beverly; Guttman-Slater, Maya; Hassan, Ayman; Henze, Megan; Kaufman, Miriam; Lawless, Bernard; Lee, Hannah; Lindzon, Lezlee; Lomax, Lysa Boissé; McAndrews, Mary Pat; Menna-Dack, Dolly; Minassian, Berge A; Mulligan, Janice; Nabbout, Rima; Nejm, Tracy; Secco, Mary; Sellers, Laurene; Shapiro, Michelle; Slegr, Marie; Smith, Rosie; Szatmari, Peter; Tao, Leeping; Vogt, Anastasia; Whiting, Sharon; Carter Snead, O

2017-09-01

The transition from a pediatric to adult health care system is challenging for many youths with epilepsy and their families. Recently, the Ministry of Health and Long-Term Care of the Province of Ontario, Canada, created a transition working group (TWG) to develop recommendations for the transition process for patients with epilepsy in the Province of Ontario. Herein we present an executive summary of this work. The TWG was composed of a multidisciplinary group of pediatric and adult epileptologists, psychiatrists, and family doctors from academia and from the community; neurologists from the community; nurses and social workers from pediatric and adult epilepsy programs; adolescent medicine physician specialists; a team of physicians, nurses, and social workers dedicated to patients with complex care needs; a lawyer; an occupational therapist; representatives from community epilepsy agencies; patients with epilepsy; parents of patients with epilepsy and severe intellectual disability; and project managers. Three main areas were addressed: (1) Diagnosis and Management of Seizures; 2) Mental Health and Psychosocial Needs; and 3) Financial, Community, and Legal Supports. Although there are no systematic studies on the outcomes of transition programs, the impressions of the TWG are as follows. Teenagers at risk of poor transition should be identified early. The care coordination between pediatric and adult neurologists and other specialists should begin before the actual transfer. The transition period is the ideal time to rethink the diagnosis and repeat diagnostic testing where indicated (particularly genetic testing, which now can uncover more etiologies than when patients were initially evaluated many years ago). Some screening tests should be repeated after the move to the adult system. The seven steps proposed herein may facilitate transition, thereby promoting uninterrupted and adequate care for youth with epilepsy leaving the pediatric system. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

PubMed

Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

2015-11-01

The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the systematic and rigorous evaluation of this form of "big data" are paramount to leverage the full potential of this new approach. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia

PubMed Central

Jehi, Lara; Friedman, Daniel; Carlson, Chad; Cascino, Gregory; Dewar, Sandra; Elger, Christian; Engel, Jerome; Knowlton, Robert; Kuzniecky, Ruben; McIntosh, Anne; O’Brien, Terence J.; Spencer, Dennis; Sperling, Michael R.; Worrell, Gregory; Bingaman, Bill; Gonzalez-Martinez, Jorge; Doyle, Werner; French, Jacqueline

2016-01-01

Summary Objective Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities. Methods We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers. Results Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis (MTS) in 1991, and three had their highest number of MTS surgeries in 2001, only one center achieved its peak number of MTS surgeries in 2011. The most productive year for MTS surgeries varied then by center; overall, the nine centers surveyed performed 48% (95% confidence interval [CI] −27.3% to −67.4%) fewer such surgeries in 2011 compared to either 1991 or 2001, whichever was higher. There was a parallel increase in the performance of surgery for nonlesional epilepsy. Further analysis of 5/9 centers showed a yearly increase of 0.6 ± 0.07% in the performance of invasive electroencephalography (EEG) without subsequent resections. Overall, although MTS was the main surgical substrate in 1991 and 2001 (proportion of total surgeries in study centers ranging from 33.3% to 70.2%); it occupied only 33.6% of all resections in 2011 in the context of an overall stable total surgical volume. Significance These findings highlight the major aspects of the evolution of epilepsy surgery across the past two decades in a sample of well-established epilepsy surgery centers, and the critical current challenges of this treatment option in addressing complex epilepsy cases requiring detailed evaluations. Possible causes and implications of these findings are discussed. PMID:26250432

Control of seizures in different stages of partial epilepsy: LACO-EXP, a Spanish retrospective study of lacosamide.

PubMed

Villanueva, Vicente; López, Francisco Javier; Serratosa, José María; González-Giraldez, Beatriz; Campos, Dulce; Molins, Albert; Rodriguez Uranga, Juan; Mauri, José Angel; Salas-Puig, Javier; Toledo, Manuel; Sánchez-Alvarez, Juan Carlos; Moreno, Antonio; Serrano-Castro, Pedro J; Saiz-Diaz, Rosa Ana; González de la Aleja, Jesús; de la Peña, Pilar; Asensio, Montserrat

2013-11-01

Lacosamide is approved as adjunctive therapy for focal epilepsies. The number of antiepileptic drugs (AEDs) tried is associated with prognosis. This multicenter, retrospective, observational study (LACO-EXP) in Spain in 500 adult patients with focal epilepsies examined the efficacy and tolerability of add-on lacosamide. Factors associated with better efficacy/tolerability were analyzed. After 12months, the responder rate (≥50% reduction in seizure frequency) was 57.1%, and the seizure-free rate was 14.9%. Efficacy was better when lacosamide was the first or second add-on AED, although there was a small chance to be seizure-free even for patients who had received ≤10 prior AEDs. The mechanism of action of concomitant AEDs is important in all the stages, but differences are smaller in the early stages. Lacosamide was generally well tolerated. A slower dosage-titration schedule was associated with a lower adverse event rate. Further investigation of the timing of initiation of lacosamide add-on therapy and ideal combinations of AEDs is required. © 2013.

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.

The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway.

PubMed

Talos, Delia M; Sun, Hongyu; Zhou, Xiangping; Fitzgerald, Erin C; Jackson, Michele C; Klein, Peter M; Lan, Victor J; Joseph, Annelise; Jensen, Frances E

2012-01-01

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.

The Interaction between Early Life Epilepsy and Autistic-Like Behavioral Consequences: A Role for the Mammalian Target of Rapamycin (mTOR) Pathway

PubMed Central

Fitzgerald, Erin C.; Jackson, Michele C.; Klein, Peter M.; Lan, Victor J.; Joseph, Annelise; Jensen, Frances E.

2012-01-01

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures. PMID:22567115

Potential implications of Luria's work for the neuropsychology of epilepsy and epilepsy surgery: A perspective for re-examination.

PubMed

Patrikelis, Panayiotis; Lucci, Giuliana; Siatouni, Anna; Verentzioti, Anastasia; Alexoudi, Athanasia; Gatzonis, Stylianos

2017-07-01

The pioneeristic work of Alexander Romanovic Luria into the field of human neuropsychology offered eminent contributions to clinical praxis by providing theory guided methods and instruments for the study of higher cortical functions. However, lots of this knowledge corpus either remains untranslated and thus inaccessible, or in some cases selectively overlooked by academic authorities and consequently not passed to the future generations of experts. Although Luria was not exclusively devoted to the study of epilepsy, his theories and clinical approaches actually penetrate the whole neuropathology spectrum. His holistic and systemic approach to the brain sounds nowadays more than opportune and consistent with the network approach of the modern neuroimaging era. As to epilepsy, the logic underlying the Lurian approach (cognitive functions organized into complex functional systems with intra- and/or inter-hemispheric distribution, as opposed to the modularistic view of the brain) seems consistent with our current knowledge in epileptology with respect to epileptic networks, as well as the modern construct of the functional deficit zone. These contributions seem to be highly promising for the neuropsychology of epilepsy and epilepsy surgery, since they provide clinicians with valuable methods and theories to assist them in the localization -and lateralization- of cognitive deficits. Consequently they are of great applicability in the context of the preoperative neuropsychological monitoring of patients candidates for epilepsy surgery, where neuropsychologist are called upon to provide surgeons with anatomical data. Copyright © 2017 Elsevier Inc. All rights reserved.

The efficacy of routine hyperventilation for seizure activation during prolonged video-electroencephalography monitoring.

PubMed

Abubakr, Abuhuziefa; Ifeayni, Iwuchukwu; Wambacq, Ilse

2010-12-01

Hyperventilation (HV) is considered to be one of the activation procedures that provokes epileptic potentials and clinical seizures. However, the true clinical yield of HV is not well established. We retrospectively reviewed the records of all patients admitted to JFK Hospital, Edison, New Jersey, between October 2001 and December 2004 for long-term video-electroencephalography (EEG). A total of 475 patients (193 males; 282 females; age range 5-89 years) were included in the study. All patients underwent routine 3-minute HV as part of the evaluation of their clinical episodes. During the initial assessment, 165 patients did not experience a seizure event, 92 had non-epileptic events, 16 experienced psychogenic non-epileptic seizures (PNES) and six had a clinical event. During HV, of the 43 patients who had primary generalized epilepsy, nine had an abnormal EEG and two experienced seizures; however, out of the 159 patients who had partial seizures, only one patient demonstrated an abnormal EEG. Our study demonstrates that routine HV generally has a very low yield in our Epilepsy-Monitoring Unit. This finding also lends support to the idea that partial seizures are relatively resistant to HV activation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Development of lacosamide for the treatment of partial-onset seizures.

PubMed

Doty, Pamela; Hebert, David; Mathy, Francois-Xavier; Byrnes, William; Zackheim, James; Simontacchi, Kelly

2013-07-01

Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy. © 2013 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Factors associated with hopelessness in epileptic patients

PubMed Central

Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Montebovi, Franco; Lamis, Dorian A; Milelli, Mariantonietta; Giuliani, Manuela; Caporro, Matteo; Tisei, Paolo; Lester, David; Amore, Mario; Girardi, Paolo; Buttinelli, Carla

2014-01-01

AIM: To investigate factors related to hopelessness in a sample of epileptic patients, including measures of depression and quality of life (QOL). METHODS: Sixty-nine participants were administered the following psychometric instruments: Beck Depression Inventory-II, Beck Hopelessness Scale (BHS), and QOL in Epilepsy (QOLIE)-89. Patients were dichotomized into two categories: those affected by epilepsy with generalized tonic-clonic seizures vs those having epilepsy with partial seizures. RESULTS: The groups differed on the QOLIE Role Limitation/Emotional dimension. Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems than patients with other types of epilepsy (89.57 ± 25.49 vs 72.86 ± 36.38; t63 = -2.16; P < 0.05). All of the respondents reported moderate to severe depression, and 21.7% of patients with generalized seizures and 28.6% of patients with other diagnoses had BHS total scores ≥ 9 indicating a higher suicidal risk. The study did not control for years of the illness. CONCLUSION: Patients with generalized seizures reported more limitations in common social/role activities related to emotional problems compared to patients with other types of seizures. Patients at increased suicide risk as evaluated by the BHS were older than those who had a lower suicidal risk. Future studies are required to further investigate the impact of hopelessness on the outcome of epileptic patients. PMID:25540729

Incidence and localizing value of vertigo and dizziness in patients with epilepsy: Video-EEG monitoring study.

PubMed

Kim, Dong Wook; Sunwoo, Jun-Sang; Lee, Sang Kun

2016-10-01

Vertigo and dizziness are common neurological complaints that have long been associated with epilepsy. However, studies of patients with epileptic vertigo or dizziness with concurrent EEG monitoring are scarce. We performed the present study to investigate the incidence and localizing value of vertigo and dizziness in patients with epilepsy who had confirmation of EEG changes via video-EEG monitoring. Data of aura and clinical seizure episodes of 831 consecutive patients who underwent video-EEG monitoring were analyzed retrospectively. Out of 831 patients, 40 patients (4.8%) experienced vertigo or dizziness as aura (mean age, 32.8±11.8years), all of whom had partial seizures. Eight had mesial temporal, 20 had lateral temporal, four had frontal, one had parietal, and seven had occipital lobe onset seizures. An intracranial EEG with cortical stimulation study was performed in seven patients, and the area of stimulation-induced vertigo or dizziness coincided with the ictal onset area in only one patient. Our study showed that vertigo or dizziness is a common aura in patients with epilepsy, and that the temporal lobe is the most frequent ictal onset area in these patients. However, it can be suggested that the symptomatogenic area in patients with epileptic vertigo and dizziness may not coincide with the ictal onset area. Copyright © 2016 Elsevier B.V. All rights reserved.

How neuropsychology can improve the care of individual patients with epilepsy. Looking back and into the future.

PubMed

Helmstaedter, Christoph; Witt, Juri-Alexander

2017-01-01

Some of the roots of current clinical neuropsychology go back to the early days of epilepsy surgery. Looking back a huge number of publications have dealt with cognition in epilepsy. The major factors driving this work were questions relating to surgery, antiepileptic drugs and, more recently, also to underlying pathology. However, most factors affecting cognition in epilepsy have been discerned many years ago. The body of neuropsychological literature in this field has accumulated much knowledge, raising the question why, apart from epilepsy surgery settings, neuropsychology has still not been fully integrated in the routine care of patients with epilepsy. This review on the occasion of Seizure's 25th anniversary attempts to summarize clinically relevant diagnostic advances following a question guided, modular, and evidence-based approach. In doing so, we hope to attract the interest of readers to an exciting mode of assessment which does not only have theoretical but also practical relevance. The comorbidities of epilepsy are becoming an increasingly relevant topic. It is now widely accepted that, while epilepsy may be defined by the occurrence of epileptic seizures, these seizures represent only one of several possible sources of cognitive impairment. It is well-established that there are complex interactions between epilepsy, cognition and behavior, and that both seizures and problems with cognition or behavior may result from a common underlying pathology requiring treatment. With this review we aim to demonstrate that neuropsychology can make a highly valuable contribution to the care of individual patients by contributing to the diagnostic process and by serving as a tool for the monitoring of disease and treatment, thereby improving the quality and safety of patient care. On a national, European, and international level, first efforts are being made to homogenize diagnostics across epilepsy centers and countries in order to achieve a common language and core standards. This should improve communication within and outside the speciality, and help to generate the data required to allow the field to make further progress. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

WONOEP appraisal: new genetic approaches to study epilepsy

PubMed Central

Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

2014-01-01

Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non-coding RNAs involved in modifying gene expression following seizures. In addition, genetically-based bioluminescent reporters are providing new opportunities to assess neuronal activity and neurotransmitter levels both in vitro and in vivo in the context of epilepsy. Finally, genetically rederived neurons generated from patient iPS cells and genetically-modified zebrafish have become high-throughput means to investigate disease mechanisms and potential new therapies. Significance Genetics has considerably changed the field of epilepsy research and is paving the way for better diagnosis and therapies for patients with epilepsy. PMID:24965021

Synchronicity and Rhythmicity of Purkinje Cell Firing during Generalized Spike-and-Wave Discharges in a Natural Mouse Model of Absence Epilepsy

PubMed Central

Kros, Lieke; Lindeman, Sander; Eelkman Rooda, Oscar H. J.; Murugesan, Pavithra; Bina, Lorenzo; Bosman, Laurens W. J.; De Zeeuw, Chris I.; Hoebeek, Freek E.

2017-01-01

Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive. Here, we investigated to what extent modulation of complex spike firing is reflected in the temporal patterns of seizures. Extracellular single-unit recordings in awake, head-restrained homozygous tottering mice, which suffer from a mutation in the voltage-gated CaV2.1 calcium channel, revealed that a substantial proportion of Purkinje cells (26%) showed increased complex spike activity and rhythmicity during GSWDs. Moreover, Purkinje cells, recorded either electrophysiologically or by using Ca2+-imaging, showed a significant increase in complex spike synchronicity for both adjacent and remote Purkinje cells during ictal events. These seizure-related changes in firing frequency, rhythmicity and synchronicity were most prominent in the lateral cerebellum, a region known to receive cerebral input via the inferior olive. These data indicate profound and widespread changes in olivary firing that are most likely induced by seizure-related activity changes in the thalamocortical network, thereby highlighting the possibility that olivary neurons can compensate for pathological brain-state changes by dampening oscillations. PMID:29163057

Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial.

PubMed

Overwater, Iris E; Rietman, André B; Bindels-de Heus, Karen; Looman, Caspar W N; Rizopoulos, Dimitris; Sibindi, Tafadzwa M; Cherian, Perumpillichira J; Jansen, Floor E; Moll, Henriëtte A; Elgersma, Ype; de Wit, Marie-Claire Y

2016-09-06

To investigate whether mammalian target of rapamycin complex 1 (mTORC1) inhibitors could reduce seizure frequency in children with tuberous sclerosis complex (TSC). Due to slow inclusion rate, target inclusion of 30 children was not reached. Twenty-three children with TSC and intractable epilepsy (age 1.8-10.9 years) were randomly assigned (1:1) to open-label, add-on sirolimus treatment immediately or after 6 months. Sirolimus was titrated to trough levels of 5-10 ng/mL. Primary endpoint was seizure frequency change during the sixth month of sirolimus treatment. Intention-to-treat analysis showed sirolimus treatment resulted in 41% seizure frequency decrease (95% confidence interval [CI] -69% to +14%; p = 0.11) compared to the standard-care period. Per protocol analysis of 14 children who reached sirolimus target trough levels in the sixth sirolimus month showed a seizure frequency decrease of 61% (95% CI -86% to +6%; p = 0.06). Cognitive development did not change. All children had adverse events. Five children discontinued sirolimus prematurely. We describe a randomized controlled trial for a non-antiepileptic drug that directly targets a presumed causal mechanism of epileptogenesis in a genetic disorder. Although seizure frequency decreased, especially in children reaching target trough levels, we could not show a significant benefit. Larger trials or meta-analyses are needed to investigate if patients with TSC with seizures benefit from mTORC1 inhibition. This trial was registered at trialregister.nl (NTR3178) and supported by the Dutch Epilepsy Foundation. This study provides Class III evidence that sirolimus does not significantly reduce seizure frequency in children with TSC and intractable epilepsy. The study lacked the precision to exclude a benefit from sirolimus. © 2016 American Academy of Neurology.

Epilepsy genetics: clinical beginnings and social consequences.

PubMed

Johnston, J A; Rees, M I; Smith, P E M

2009-07-01

The approach to epilepsy care has transformed in the last 30 years, with more and better anti-epileptic medications, improved cerebral imaging and increased surgical options. Alongside this, developments in neuroscience and molecular genetics have furthered the understanding of epileptogenesis. Future developments in pharmacogenomics hold the promise of antiepileptic drugs matched to specific genotypes. Despite this rapid progress, one-third of epilepsy patients remain refractory to medication, with their seizures impacting upon day-to-day activity, social well-being, independence, economic output and quality of life. International genome collaborations, such as HapMap and the Welcome Trust Case-Control Consortium single nucleotide polymorphism (SNP) mapping project have identified common genetic variations in diseases of major public health importance. Such genetic signposts should help to identify at-risk populations with a view to producing more effective pharmaceutical treatments. Neurological disorders, despite comprising one-fifth of UK acute medical hospital admissions, are surprisingly under-represented in these projects. Epilepsy is the commonest serious neurological disorder worldwide. Although physically, psychologically, socially and financially disabling, it rarely receives deserved attention from physicians, scientists and governmental bodies. As outlined in this article, research into epilepsy genetics presents unique challenges. These help to explain why the identification of its complex genetic traits has lagged well behind other disciplines, particularly the efforts made in neuropsychiatric disorders. Clinical beginnings must underpin any genetic understanding in epilepsy. Success in identifying genetic traits in other disorders does not make the automatic case for genome-wide screening in epilepsy, but such is a desired goal. The essential clinical approach of accurately phenotyping, diagnosing and interpreting the dynamic nature of epilepsy remains fundamental to harvesting its potential translational outcomes.

Treatment issues for children with epilepsy transitioning to adult care.

PubMed

Nabbout, Rima; Camfield, Carol S; Andrade, Danielle M; Arzimanoglou, Alexis; Chiron, Catherine; Cramer, Joyce A; French, Jacqueline A; Kossoff, Eric; Mula, Marco; Camfield, Peter R

2017-04-01

This is the third of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper focuses on treatment issues that arise during the course of childhood epilepsy and make the process of transition to adult care more complicated. Some AEDs used during childhood, such as stiripentol, vigabatrin, and cannabidiol, are unfamiliar to adult epilepsy specialists. In addition, new drugs are being developed for treatment of specific childhood onset epilepsy syndromes and have no indication yet for adults. The ketogenic diet may be effective during childhood but is difficult to continue in adult care. Regional adult epilepsy diet clinics could be helpful. Polytherapy is common for patients transitioning to adult care. Although these complex AED regimes are difficult, they are often possible to simplify. AEDs used in childhood may need to be reconsidered in adulthood. Rescue medications to stop prolonged seizures and clusters of seizures are in wide home use in children and can be continued in adulthood. Adherence/compliance is notoriously difficult for adolescents, but there are simple clinical approaches that should be helpful. Mental health issues including depression and anxiety are not always diagnosed and treated in children and young adults even though effective treatments are available. Attention deficit hyperactivity disorder and aggressive behavior disorders may interfere with transition and successful adulthood but these can be treated. For the majority, the adult social outcome of children with epilepsy is unsatisfactory with few proven interventions. The interface between pediatric and adult care for children with epilepsy is becoming increasingly complicated with a need for more comprehensive transition programs and adult epileptologists who are knowledgeable about special treatments that benefit this group of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish.

PubMed

de Calbiac, Hortense; Dabacan, Adriana; Marsan, Elise; Tostivint, Hervé; Devienne, Gabrielle; Ishida, Saeko; Leguern, Eric; Baulac, Stéphanie; Muresan, Raul C; Kabashi, Edor; Ciura, Sorana

2018-05-01

DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders. In this study, we defined the expression of depdc5 during development and established an epilepsy model with reduced Depdc5 expression. Here we report a zebrafish model of Depdc5 loss-of-function that displays a measurable behavioral phenotype, including hyperkinesia, circular swimming, and increased neuronal activity. These phenotypic features persisted throughout embryonic development and were significantly reduced upon treatment with the mTORC1 inhibitor, rapamycin, as well as overexpression of human WT DEPDC5 transcript. No phenotypic rescue was obtained upon expression of epilepsy-associated DEPDC5 mutations (p.Arg487* and p.Arg485Gln), indicating that these mutations cause a loss of function of the protein. This study demonstrates that Depdc5 knockdown leads to early-onset phenotypic features related to motor and neuronal hyperactivity. Restoration of phenotypic features by WT but not epilepsy-associated Depdc5 mutants, as well as by mTORC1 inhibition confirm the role of Depdc5 in the mTORC1-dependent molecular cascades, defining this pathway as a potential therapeutic target for DEPDC5 -inherited forms of focal epilepsy.

Understanding relationships between autism, intelligence, and epilepsy: a cross-disorder approach

PubMed Central

VAN EEGHEN, AGNIES M; PULSIFER, MARGARET B; MERKER, VANESSA L; NEUMEYER, ANN M; VAN EEGHEN, ELMER E; THIBERT, RONALD L; COLE, ANDREW J; LEIGH, FAWN A; PLOTKIN, SCOTT R; THIELE, ELIZABETH A

2014-01-01

Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were filled out in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 4–63y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y range 4–22y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism. Interpretation Our data show that in TSC and childhood-onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific for these conditions. PMID:23205844

A Complex Contraception Registry

ClinicalTrials.gov

2018-03-13

Diabetes; Cardiovascular Disease; Epilepsy; Migraine; Neurological Disorders; Cancer; Bariatric Surgery Candidate; Organ or Tissue Transplant; Complications; Lupus Erythematosus, Systemic; Other Hematologic Conditions; Other Venous Embolism and Thrombosis

Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review.

PubMed

Nolan, Sarah J; Marson, Anthony G; Weston, Jennifer; Tudur Smith, Catrin

2015-08-14

This is an updated version of the original Cochrane review published in Issue 2, 2002 and its subsequent update in 2010.Epilepsy is a common neurological condition in which recurrent, unprovoked seizures are caused by abnormal electrical discharges from the brain. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenytoin are commonly used broad spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first line treatment for partial onset seizures in the USA and Europe. Phenytoin is no longer considered a first line treatment due to concerns over adverse events associated with its use, however the drug is still commonly used in low- to middle-income countries due to it's low cost. No consistent differences in efficacy have been found between carbamazepine and phenytoin in individual trials, however the confidence intervals generated by these studies are wide. Therefore, differences in efficacy may be shown by synthesising the data of the individual trials. To review the time to withdrawal, six- and 12-month remission, and first seizure of carbamazepine compared to phenytoin when used as monotherapy in people with partial onset seizures (simple partial, complex partial, or secondarily generalised tonic-clonic seizures) or generalised tonic-clonic seizures, with or without other generalised seizure types. We searched the Cochrane Epilepsy Group's Specialised Register (16 September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8), MEDLINE (1946 to 16 September 2014), SCOPUS (1823 to 16 September 2014), ClinicalTrials.gov (16 September 2014), and the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP (18 September 2014). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field. Randomised controlled trials (RCTs) in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of carbamazepine monotherapy versus phenytoin monotherapy. This was an individual participant data (IPD) review. Our primary outcome was time to withdrawal of allocated treatment, and our secondary outcomes were time to 12-month remission, time to six-month remission and time to first seizure post-randomisation. We used Cox proportional hazards regression models to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) and the generic inverse variance method to obtain the overall pooled HR and 95% CI. IPD were available for 595 participants out of 1192 eligible individuals, from four out of 12 trials (i.e. 50% of the potential data). For remission outcomes, HR > 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, HR > 1 indicates an advantage for carbamazepine. Methodological quality of the four studies providing IPD was generally good and we rated it at low risk of bias overall in the analyses.The main overall results (pooled HR adjusted for seizure type) were time to withdrawal of allocated treatment: 1.04 (95% CI 0.78 to 1.39); time to 12-month remission: 1.01 (95% CI 0.78 to 1.31); time to six-month remission: 1.11 (95% CI 0.81 to 1.37); and time to first seizure: 0.85 (95% CI 0.70 to 1.04). The results suggest no overall statistically significant difference between the drugs for these outcomes. There is some evidence of an advantage for phenytoin for individuals with generalised onset seizures for our primary outcome (time to withdrawal of allocated treatment): pooled HR 0.42 (95% CI 0.18 to 0.96); and a statistical interaction between treatment effect and epilepsy type (partial versus generalised) for this outcome (P = 0.02), however misclassification of seizure type for up to 48 individuals (32% of those with generalised epilepsy) may have confounded the results of this review. Despite concerns over side effects leading to the withdrawal of phenytoin as first line treatment in the USA and Europe, we found no evidence that phenytoin is more likely to be associated with serious side effects than carbamazepine; 26 individuals withdrew from 290 randomised (9%) to carbamazepine due to adverse effects compared to 12 out of 299 (4%) randomised to phenytoin from four studies conducted in the USA and Europe (risk ratio (RR) 1.42, 95% CI 1.13 to 1.80, P = 0.014). We rated the quality of the evidence as low - moderate according to GRADE criteria, due to imprecision and potential misclassification of seizure type. We have not found evidence that a statistically significant difference exists between carbamazepine and phenytoin for the efficacy outcomes examined in this review, however, CIs are wide and the possibility of important differences existing has not been excluded. There is no evidence in this review that phenytoin is more strongly associated with serious adverse events than carbamazepine. There is some evidence that participants with generalised seizures may be less likely to withdraw early from phenytoin than carbamazepine, but misclassification of seizure type may have impacted upon the results of this review. We recommend caution when interpreting the results of this review, and do not recommend that the results of this review alone should be used in choosing between carbamazepine and phenytoin. We recommend that future trials should be designed to the highest quality possible with considerations on allocation concealment and masking, choice of population, choice of outcomes and analysis, and presentation of results.

Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

PubMed

Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

2016-06-01

Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Nap polygraphic recordings after partial sleep deprivation in patients with suspected epileptic seizures.

PubMed

Peraita-Adrados, R; Gutierrez-Solana, L; Ruiz-Falcó, M L; García-Peñas, J J

2001-02-01

A review of the literature shows that nap recordings make a significant contribution to epilepsy studies, providing evidence of specific EEG findings in patients suspected of having epilepsy. In addition, sleep deprivation can cause paroxysmal EEG activity and clinical seizures. We studied retrospectively 686 patients, 51.8% males and 48.2% females, who had experienced at least one episode classified from the clinical point of view as epileptic in origin. They were divided into six age groups. Patients underwent a two-hour (1 P.M.-3 P.M.) nap-video-polygraphic recording (EEG 13 channels using the standard 10-20 system, EOG, ECG, EMG and respiration), following a partial sleep deprivation (1 to 3 h) the night before. A second recording was made in 40 patients. In 35.3% of patients, a complete sleep cycle was obtained; in 64.6% sufficient light and deep NREM sleep was obtained, but not REM stage; in 9.3%, we only observed drowsiness and stage 1 of sleep, and this group was excluded from the analysis. Interictal and/or ictal epileptic discharges were observed during the first nap recording in 245 patients (40.4% of the sample). In addition, in 40 patients (11%) with normal or inconclusive first nap EEG, a second recording was able to demonstrate epileptic abnormalities in 35% of cases. Because of its good cost/benefit ratio and availability in most western laboratories, we consider the 'nap plus partial sleep deprivation' method as advantageous over other activation procedures.

Low-frequency repetitive transcranial magnetic simulation prevents chronic epileptic seizure

PubMed Central

Wang, Yinxu; Wang, Xiaoming; Ke, Sha; Tan, Juan; Hu, Litian; Zhang, Yaodan; Cui, Wenjuan

2013-01-01

Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcranial magnetic simulation on changes in several nonlinear dynamic electroence-phalographic parameters in rats with chronic epilepsy and explored the mechanism underlying petitive transcranial magnetic simulation-induced antiepileptic effects. An epilepsy model was es-tablished using lithium-pilocarpine intraperitoneal injection into adult Sprague-Dawley rats, which were then treated with repetitive transcranial magnetic simulation for 7 consecutive days. Nonlinear electroencephalographic parameters were obtained from the rats at 7, 14, and 28 days post-stimulation. Results showed significantly lower mean correlation-dimension and Kolmogo-rov-entropy values for stimulated rats than for non-stimulated rats. At 28 days, the complexity and point-wise correlation dimensional values were lower in stimulated rats. Low-frequency repetitive transcranial magnetic simulation has suppressive effects on electrical activity in epileptic rats, thus explaining its effectiveness in treating epilepsy. PMID:25206567

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

Knowledge and attitudes toward epilepsy amongst students in the health area: intervention aimed at enlightenment.

PubMed

Tedrus, Glória Maria A S; Fonseca, Lineu Corrêa; Vieira, Ana Lídia da Câmara

2007-12-01

It is known that there is a lack of knowledge about epilepsy amongst the population in general, with consequent prejudice and discrimination towards epileptic patients. Considering the importance of health professionals in the diffusion of knowledge about this neurological condition, the objective of the present study was to evaluate modifications in the knowledge and attitudes of students in the health area with respect to epilepsy, after an intervention including the presentation of specific audio-visual material and a discussion on the basic aspects of epilepsy. Simple self-administered questionnaires were applied to one hundred and sixteen health area students before and after the session of enlightenment. After the session there was significant (p<0.05) improvement in answers to different questions about etiology, epidemiology, education, work, and attitude during the seizure. The results suggest the need to include a routine low complexity educational activity in the curriculum of various courses in the health area.

Seizure Action Plans Do Not Reduce Health Care Utilization in Pediatric Epilepsy Patients.

PubMed

Roundy, Lindsi M; Filloux, Francis M; Kerr, Lynne; Rimer, Alyssa; Bonkowsky, Joshua L

2016-03-01

Management of pediatric epilepsy requires complex coordination of care. We hypothesized that an improved seizure management care plan would reduce health care utilization and improve outcomes. The authors conducted a cohort study with historical controls of 120 epilepsy patients before and after implementation of a "Seizure Action Plan." The authors evaluated for differences in health care utilization including emergency department visits, hospitalizations, clinic visits, telephone calls, and the percentage of emergency department visits that resulted in hospitalization in patients who did or did not have a Seizure Action Plan. The authors found that there was no decrease in these measures of health care utilization, and in fact the number of follow-up clinic visits was increased in the group with Seizure Action Plans (4.2 vs 3.3, P = .006). However, the study was underpowered to detect smaller differences. This study suggests that pediatric epilepsy quality improvement measures may require alternative approaches to reduce health care utilization and improve outcomes. © The Author(s) 2015.

Seizure Action Plans Do Not Reduce Health Care Utilization in Pediatric Epilepsy Patients

PubMed Central

Roundy, Lindsi M.; Filloux, Francis M.; Kerr, Lynne; Rimer, Alyssa; Bonkowsky, Joshua L.

2015-01-01

Management of pediatric epilepsy requires complex coordination of care. We hypothesized that an improved seizure management care plan would reduce healthcare utilization and improve outcomes. We conducted a cohort study with historical controls of 120 epilepsy patients before and after implementation of a “Seizure Action Plan.” We evaluated for differences in healthcare utilization including emergency department visits, hospitalizations, clinic visits, telephone calls, and the percentage of emergency department visits that resulted in hospitalization in patients who did or did not have a Seizure Action Plan. We found that there was no decrease in these measures of healthcare utilization, and in fact the number of follow-up clinic visits was increased in the group with Seizure Action Plans (4.2 versus 3.3, p 0.006). However, the study was underpowered to detect smaller differences. Our study suggests that pediatric epilepsy quality improvement measures may require alternative approaches to reduce healthcare utilization and improve outcomes. PMID:26245799

Child- and parent-reported quality of life trajectories in children with epilepsy: A prospective cohort study.

PubMed

Ferro, Mark A; Avery, Lisa; Fayed, Nora; Streiner, David L; Cunningham, Charles E; Boyle, Michael H; Lach, Lucyna; Glidden, Gina; Rosenbaum, Peter L; Ronen, Gabriel M

2017-07-01

To describe the developmental trajectories of quality of life (QoL) in a large cohort of children with epilepsy, and to assess the relative contribution of clinical, psychosocial, and sociodemographic variables on QoL trajectories. Five assessments during a 28-month prospective cohort study were used to model trajectories of QoL. Participants were recruited with their parents from six Canadian tertiary centers. A convenience sample of 506 children aged 8-14 years with epilepsy and without intellectual disability or autism spectrum disorder were enrolled. A total of 894 children were eligible and 330 refused participation. Participating children were, on average, 11.4 years of age, and 49% were female. Nearly one third (32%) had partial seizures. At baseline, 479 and 503 child- and parent-reported questionnaires were completed. In total, 354 children (74%) and 366 parents (73%) completed the 28-month follow-up. QoL was measured using the child- and parent-reported version of the Childhood Epilepsy QoL scale (CHEQOL-25). Child-reported QoL was fitted best by a six-class model and parent-reported QoL by a five-class model. In both models, trajectories remained either stable or improved over 28 months. Of these children, 62% rated their QoL as high or moderately high, defined as at least one standard deviation above the average CHEQOL-25 score. Greater family, classmate, and peer social support, fewer symptoms of child and parent depression, and higher receptive vocabulary were identified as the most robust predictors of better QoL (all p < 0.001). Most children with epilepsy and their parents reported relatively good QoL in this first joint self- and proxy-reported trajectory study. Findings confirm the heterogeneous QoL outcomes for children with epilepsy and the primary importance of psychosocial factors rather than seizure and AED-specific factors in influencing QoL. These predictors that are potentially amenable to change should now be the focus of specific intervention studies. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Subependymal heterotopia: a distinct neuronal migration disorder associated with epilepsy.

PubMed Central

Raymond, A A; Fish, D R; Stevens, J M; Sisodiya, S M; Alsanjari, N; Shorvon, S D

1994-01-01

Subependymal heterotopia has recently been recognised as a cause of epilepsy, but the clinical and investigational features have not been fully described. The clinical, psychometric, imaging, and electroencephalographic features of 13 adult patients with subependymal heterotopia and epilepsy have been reviewed. Age at seizure onset ranged from 18 months to 20 years (median 13 years). There were significantly more female (12) than male (1) patients (p < 0.01). Diagnosis of subependymal heterotopia was made by MRI in 11 patients and CT in two. The heterotopic grey matter was nodular in 11 patients and diffuse in two; bilateral in eight and unilateral in five. There were significantly more patients with predominant right than left cerebral hemisphere involvement (p < 0.01). The most commonly involved site was the occipital horn of the lateral ventricles (10 of 13 patients). Eleven patients presented with partial epilepsy, 10 of whom also had secondarily generalised seizures. The clinical description of the seizures often suggested either an occipital (four patients) or temporal (five patients) onset. Two patients presented with absence attacks without clear focal features. Patients demonstrated normal early milestones (12 of 13 patients), including normal motor development (all patients) and average or above average intelligence (10 of 13 patients). An EEG examination showed normal background activity in all but two patients, one of whom had large intracranial haematomas. Epileptiform activity was usually widespread (10 of 13 patients) and in three patients, there was generalised 3-Hz spike and wave activity that had previously led to an erroneous diagnosis of concomitant primary generalised epilepsy. Onset of epilepsy in the second decade of life, normal developmental milestones and intelligence, and the finding of an overwhelming female preponderance differentiates subependymal heterotopia from other cortical dysgeneses. The female preponderance supports the importance of the X chromosome and sex steroids in the maturation and development of the cerebral cortex. Images PMID:7931380

Influence of fatigue, depression, and demographic, socioeconomic, and clinical variables on quality of life of patients with epilepsy.

PubMed

Senol, Vesile; Soyuer, Ferhan; Arman, Fehim; Oztürk, Ahmet

2007-02-01

The purpose of this study was to define the influence of fatigue, depression, and clinical, demographic, and socioeconomic factors on the quality of life of patients with epilepsy. The study was performed on 103 adult patients who visited Erciyes University Epilepsy Outpatient Clinic between 2004 and 2005. Patients were evaluated with the Form of Negotiation, Quality of Life in Epilepsy Inventory (QOLIE-89), Beck Depression Inventory, and Fatigue Severity Scale. Mean age of the patients was 34.3+/-12.6, and mean duration of disease was 12.6+/-9.3 years. Among these patients, 52.4% were men, 49.5% were married, 15.5% had a university education, 53.4% had low incomes, 45.6% had generalized seizures, and 35.0% had experienced one or more seizures per month during the preceding year. The most significant variables in the domain of Overall quality of life were seizure frequency (P<0.001), depression (P<0.001), and fatigue (P<0.001); the variables in the domain of Mental Health were seizure frequency (P<0.001) and fatigue (P<0.001); the variable in the Cognitive domain was fatigue (P<0.001); the variables in the domain of Physical Health were social insurance coverage (P<0.01), fatigue (P<0.01), and age (P<0.01); the variables in the Epilepsy Targeted domain were depression (P<0.001), seizure frequency (P<0.001), and fatigue (P<0.01). Although quality of life has multiple determinants, seizure frequency, fatigue, and depression are the most important factors affecting quality of life in patients with epilepsy. One or more seizures per month, severe fatigue, and depression are associated with lower quality of life in some but not all domains. Partial correlations demonstrated that fatigue was a significant independent predictor of quality of life. The present study confirms that fatigue can be a powerful predictor of quality of life.

Wordless intervention for people with epilepsy and learning disabilities (WIELD): a randomised controlled feasibility trial

PubMed Central

Mengoni, Silvana E; Gates, Bob; Parkes, Georgina; Wellsted, David; Barton, Garry; Ring, Howard; Khoo, Mary Ellen; Monji-Patel, Deela; Friedli, Karin; Zia, Asif; Irvine, Lisa; Durand, Marie-Anne

2016-01-01

Objective To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. Trial design A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Setting Epilepsy clinics in 1 English National Health Service (NHS) Trust. Participants Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Intervention Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. Outcome measures 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. Outcome The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. Conclusions All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. Trial registration number ISRCTN80067039. PMID:28186943

Wordless intervention for people with epilepsy and learning disabilities (WIELD): a randomised controlled feasibility trial.

PubMed

Mengoni, Silvana E; Gates, Bob; Parkes, Georgina; Wellsted, David; Barton, Garry; Ring, Howard; Khoo, Mary Ellen; Monji-Patel, Deela; Friedli, Karin; Zia, Asif; Irvine, Lisa; Durand, Marie-Anne

2016-11-10

To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Epilepsy clinics in 1 English National Health Service (NHS) Trust. Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. ISRCTN80067039. 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/.

Early neurodevelopmental screening in tuberous sclerosis complex: a potential window of opportunity.

PubMed

Gipson, Tanjala T; Gerner, Gwendolyn; Srivastava, Siddharth; Poretti, Andrea; Vaurio, Rebecca; Hartman, Adam; Johnston, Michael V

2014-09-01

Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. Many risk factors have been associated with intellectual disability and/or autism in individuals with tuberous sclerosis complex; however, few data are available regarding practical clinical tools for early identification. In our case series, inclusion of the Capute Scales as a part of routine medical care led to the identification of developmental delays in the first 12 months of life and selection of targeted neurodevelopmental interventions. Development of a risk-based assessment using this approach will be the focus of future studies as it may provide a potential window of opportunity for both research and clinical purposes. In research, it may serve as an objective outcome measure. Clinically, this type of assessment has potential for informing clinical treatment decisions and serving as a prognostic indicator of long-term cognitive and psychiatric outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Effective process or dangerous precipice: qualitative comparative embedded case study with young people with epilepsy and their parents during transition from children’s to adult services

PubMed Central

2013-01-01

Background Transition from children’s to adult epilepsy services is known to be challenging. Some young people partially or completely disengage from contact with services, thereby risking their health and wellbeing. We conducted a mixed-method systematic review that showed current epilepsy transition models enabling information exchange and developing self-care skills were not working well. We used synthesised evidence to develop a theoretical framework to inform this qualitative study. The aim was to address a critical research gap by exploring communication, information needs, and experiences of knowledge exchange in clinical settings by young people and their parents, during transition from children’s to adult epilepsy services. Method Qualitative comparative embedded Case study with 2 'transition’ cases (epilepsy services) in two hospitals. Fifty-eight participants: 30 young people (13–19 years) and 28 parents were interviewed in-depth (individual or focus group). Clinical documents/guidelines were collated. 'Framework’ thematic analysis was used. The theoretical framework was tested using themes, pattern matching and replication logic. Theory-based evaluation methods were used to understand how and why different models of service delivery worked. Results A joint epilepsy clinic for young people 14–17 years coordinated by children’s and adult services was more likely to influence young people’s behaviour by facilitating more positive engagement with adult healthcare professionals and retention of epilepsy-related self-care information. Critical success factors were continuity of care, on-going and consistent age-appropriate and person centred communication and repeated information exchange. Three young people who experienced a single handover clinic disengaged from services. Psychosocial care was generally inadequate and healthcare professionals lacked awareness of memory impairment. Parents lacked knowledge, skills and support to enable their child to independently self-care. Translation of transition policies/guidelines into practice was weak. Conclusion Findings make a significant contribution to understanding why young people disengage from epilepsy services, why some parents prevent independent self-care, and what constitutes good communication and transition from the perspective of young people and parents. The type of service configuration, delivery and organisation influenced the behaviours of young people at transition to adult services. The novel theoretical framework was substantially supported, underwent further post-hoc development and can be used in future practice/intervention development and research. PMID:24131769

Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review

PubMed Central

Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.

2016-01-01

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID:27255267

Genetic testing in the epilepsies—Report of the ILAE Genetics Commission

PubMed Central

Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.

2010-01-01

SUMMARY In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high0020clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225

Chess-playing epilepsy: a case report with video-EEG and back averaging.

PubMed

Mann, M W; Gueguen, B; Guillou, S; Debrand, E; Soufflet, C

2004-12-01

A patient suffering from juvenile myoclonic epilepsy experienced myoclonic jerks, fairly regularly, while playing chess. The myoclonus appeared particularly when he had to plan his strategy, to choose between two solutions or while raising the arm to move a chess figure. Video-EEG-polygraphy was performed, with back averaging of the myoclonus registered during a chess match and during neuropsychological testing with Kohs cubes. The EEG spike wave complexes were localised in the fronto-central region. [Published with video sequences].

[Clinical and electrophysiologic studies on epileptic negative myoclonus in atypical benign partial epilepsy of childhood].

PubMed

Yang, Zhi-xian; Liu, Xiao-yan; Qin, Jiong; Zhang, Yue-hua; Bao, Xin-hua; Chang, Xing-zhi; Wu, Ye; Xiong, Hui

2008-12-01

To investigate the clinical, neurophysiologic characteristics and therapeutic considerations of epileptic negative myoclonus (ENM) in atypical benign partial epilepsy of childhood (ABPE). Video-EEG monitoring with outstretched arm tests were carried out in 17 patients, and 9 of them were examined with simultaneous electromyography (EMG). The ENM manifestations, electrophysiologic features and responses to antiepileptic drugs (AED) were analyzed. Seventeen patients were diagnosed as having benign childhood epilepsy with centrotemporal spikes (BECT) during the early course of the disease and were treated with AED. During the course of the disease, hand trembling, objects dropping, head nodding and instability during standing might be clues for ENM occurrence. ENM had been confirmed in our patients by outstretched arm tests during video-EEG recording. The ictal EEG showed that high-amplitude spikes followed by a slow wave over the contralateral motor areas. This was further confirmed by time-locked silent EMG in 9 patients. During ENM occurrence or recurrence, the habitual seizures and interictal discharges were exaggerated. Atypical absence seizures also occurred in 6 patients. The alteration of therapeutic options of AED relating to ENM appearance in some patients included the add-on therapy with carbamazepine (CBZ), oxcarbazepine, phenobarbital, or withdrawal of valproate (VPA). ENM was controlled in most cases by using VPA, clonazepam (CZP) and corticosteroid with different combination. ENM could occur during the course of ABPE. Outstretching arm tests during video-EEG monitoring in combination with EMG was essential to confirm ENM. The ENM occurrence was always associated with the frequency increasing of habitual seizures and the aggravation of interictal discharges. Some AED such as CBZ might induce ENM. VPA, benzodiazepines and corticosteroid with different combination were relatively effective in treatment of ENM.

Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task.

PubMed

Tang, Yingying; Xia, Wei; Yu, Xiaofeng; Zhou, Bo; Wu, Xintong; Lui, Su; Luo, Chunyan; Huang, Xiaoqi; Ouyang, Luo; Chen, Qin; Gong, Qiyong; Zhou, Dong

2016-06-01

Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

Ischemic Stroke and Epilepsy in a Patient with Tourette´s Syndrome: Association with the Antiphospholipid Syndrome and Good Response to Levetiracetam

PubMed Central

Seijo-Martínez, M; Mosquera-Martínez, J.A; Romero-Yuste, S; Cruz-Martinez, J

2008-01-01

The role played by different humoral factors, including antiphospholipid antibodies, in the pathogenesis of Tourette syndrome (TS) is still presently unclear. We present a patient with chronic and severe TS who, at the age of 16 years, presented an ischemic stroke in the left posterior cerebral artery and/or postero-inferior temporal branch of the left medial cerebral artery. A complete study was negative with the exception of a positive lupus anticoagulant. The stroke was related with the primary antiphospholipid syndrome (APS). The stroke manifested visual abnormalities and thereafter by secondary generalized complex partial seizures. The epileptic syndrome was initially difficult to control but responded dramatically to levetiracetam. With this therapy, the manifestations of TS, especially the tics, improved. We conclude that some TS cases may present APS. In addition, levetiracetam may be useful in the management of TS. Further investigations should pursue both these facts. PMID:19018305

The neuropsychiatric ailment of Vincent Van Gogh

PubMed Central

Bhattacharyya, Kalyan B.; Rai, Saurabh

2015-01-01

Vincent Van Gogh is one of the most celebrated creative artists of all time. All his life, he was afflicted by some kind of neurological or psychiatric disorder, which remains a mystery even today. Many historians and his personal physicians believe that he suffered from epilepsy while others felt that he was affected by Ménière's disease. Features such as hypergraphia, atypical sexuality, and viscosity of thinking suggest the possibility of Gastaut-Geschwind phenomenon, a known complication of complex partial seizure. On the contrary, some historians feel that he was forced to sever his right ear in order to get relief from troublesome tinnitus, a complication of Ménière's disease. He was addicted to the liquor absinthe, which is known to lead to xanthopsia, and many authorities argue that this was the reason for his penchant for the deep and bright yellow color in many of his paintings. Others have suggested the possibility of bipolar disorder, sunstroke, acute intermittent porphyria, and digitalis toxicity as well. PMID:25745302

Measurement of Local Partial Pressure of Oxygen in the Brain Tissue under Normoxia and Epilepsy with Phosphorescence Lifetime Microscopy.

PubMed

Zhang, Cong; Bélanger, Samuel; Pouliot, Philippe; Lesage, Frédéric

2015-01-01

In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure.

[Professional activity of people with epilepsy].

PubMed

Staniszewska, Anna; Sobiecki, Marcin; Duda-Zalewska, Aneta; Religioni, Urszula; Juszczyk, Grzegorz; Tatara, Tomasz; Słoniewski, Robert

2015-01-01

The aim of the study was to determine the occupational activity of epileptic patients. Particular attention was paid to employment of people with epilepsy, the way the workplace is informed about the disease, impact of education on employment opportunities and the relationship between clinical type of epilepsy and professional activity. Patients were recruited from the neurological outpatient clinic in Warszawa and asked to fill in a customized questionnaire, containing questions on their socio-demographic, clinical and employment status. The study included 197 adult patients with epilepsy (64 professionally active and 133 inactive). As many as 47.7% of respondents declared that the disease impeded their employment, and 77.2% admitted that the occurrence of seizure at work had negatively affected their comfort. As many as 42.2% professionally active respondents had revealed the disease at work. There was a statistically significant difference between individuals with primarily generalized seizures and those with partial and secondarily generalized seizures (30.61% vs. 2.63%, p<0.05). Education had also a significant positive impact on employment (47.06% employed with university degree vs. 9.76% with primary education, p<0.05). No significant correlations between duration of the disease or number of the epileptic seizures, independent of their type and revealing the disease in the workplace, were observed (p>0.05). Neither current work status had impact on opinions about difficulties in finding a job (p>0.05). Epilepsy is a great obstacle to finding and maintaining employment. Less than 1/2 of patients inform the workplace about their illness, mainly due to previous negative experiences. Since education significantly enables the employment, programs aimed at promoting vocational activation of patients should facilitate access to learning. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Cognitive functioning in dyskinetic cerebral palsy: Its relation to motor function, communication and epilepsy.

PubMed

Ballester-Plané, Júlia; Laporta-Hoyos, Olga; Macaya, Alfons; Póo, Pilar; Meléndez-Plumed, Mar; Toro-Tamargo, Esther; Gimeno, Francisca; Narberhaus, Ana; Segarra, Dolors; Pueyo, Roser

2018-01-01

Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors. To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments. Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS. Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II-III also showed impairment in language-related functions. Severe cases (GMFCS IV-V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning. Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.

PubMed

Nemes, Ashley D; O'Dwyer, Rebecca; Najm, Imad M; Ying, Zhong; Gonzalez-Martinez, Jorge; Alexopoulos, Andreas V

2017-10-01

Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA A ) antagonist used to provoke generalized seizures as a "second hit." LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Intractable epilepsy and structural lesions of the brain: mapping, resection strategies, and seizure outcome.

PubMed

Awad, I A; Rosenfeld, J; Ahl, J; Hahn, J F; Lüders, H

1991-01-01

Forty-seven patients with structural brain lesions on neuroimaging studies and partial epilepsy intractable to medical therapy were studied. Prolonged noninvasive interictal and ictal EEG recording was performed, followed by more focused mapping using chronically implanted subdural electrode plates. Surgical procedures included lesion biopsy, maximal lesion excision, and/or resection of zones of epileptogenesis depending on accessibility and involvement of speech or other functional areas. The epileptogenic zone involved exclusively the region adjacent to the structural lesion in 11 patients. It extended beyond the lesion in 18 patients. Eighteen other patients had remote noncontiguous zones of epileptogenesis. Postoperative control of epilepsy was accomplished in 17 of 18 patients (94%) with complete lesion excision regardless of extent of seizure focus excision. Postoperative control of epilepsy was accomplished in 5 of 6 patients (83%) with incomplete lesion excision but complete seizure focus excision and in 12 of 23 patients (52%) with incomplete lesion excision and incomplete focus excision. The extent of lesion resection was strongly associated with surgical outcome either in itself (p less than 0.003), or in combination with focus excision. Focus resection was marginally associated with surgical outcome as a dichotomous variable (p = 0.048) and showed a trend toward significance (p = 0.07) only as a three-level outcome variable. We conclude that structural lesions are associated with zones of epileptogenesis in neighboring and remote areas of the brain. Maximum resection of the lesion offers the best chance at controlling intractable epilepsy; however, seizure control is achieved in many patients by carefully planned subtotal resection of lesions or foci.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of Time and Frequency Domain Parameters of Heart Rate Variability and Interictal Cardiac Rhythm Abnormalities in Drug-naïve Patients with Idiopathic Generalized Epilepsy

PubMed Central

Kilinc, Ozden; Cincin, Altug; Pehlivan, Aslihan; Midi, Ipek; Kepez, Alper; Agan, Kadriye

2016-01-01

Background and Purpose: Epilepsy is a disease known to occur with autonomous phenomenons. Earlier studies indicate decreased heart rate variability (HRV) during ictal and interictal periods among epilepsy patients. In this study, we aim to investigate cardiac rhythm abnormalities and HRV during interictal period between drug-naïve patients with idiopathic generalized epilepsy (IGE) and healthy control group. Methods: Twenty-six patients with IGE and 26 healthy individuals included in the study. In order to eliminate any structural cardiac pathology, transthoracic echocardiography was performed in all subjects and time and frequency domain parameters of HRV were evaluated after 24-hour rhythm holter monitoring. Results: Between two groups, no significant difference was detected in terms of mean heart rate and maximum duration between the start of the Q waves and the end of the T waves (QT intervals). In the time domain analysis of HRV, no statically significant difference was detected for standard deviation of all R - R intervals and root-mean-square of successive differences between patient and control group (p = 0,070 and p = 0,104 respectively). In the frequency domain analysis of HRV, patients tended to display lower total power and very low frequency power than did healthy subjects, but the differences were not statistically significant. Conclusions: Our results suggest that there is no major effect of the epilepsy on HRV in patients with IGE. It should be emphasized that, in this study, HRV was evaluated only in patients with IGE and that the results are not proper to be generalized for patients with partial seizures. PMID:27390676

[Epilepsy and psychic seizures].

PubMed

Fukao, Kenjiro

2006-01-01

Various psychic symptoms as ictal manifestation have been found in epileptic patients. They are classified as psychic seizures within simple partial seizures, and subclassified into affective, cognitive, dysmnesic seizures and so on, although the subclassification is not yet satisfactory and almost nothing is known about their relationships with normal brain functions. In this presentation, the speaker picked ictal fear, déjà vu and out-of-body experience (OBE) from them and suggested that studies on these symptoms could uniquely contribute to the progress of cognitive neuroscience, presenting some results from the research and case study that he had been engaged in. Psychic seizures are prone to be missed or misdiagnosed unless psychiatrists with sufficient knowledge and experience on epilepsy care would not treat them, because they are subjective symptoms that are diverse and subtle, while they have some characteristics as ictal symptoms.

Methodological issues associated with clinical trials in epilepsy.

PubMed

Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Russo, Emilio; Cianci, Vittoria; Ascoli, Michele; De Sarro, Giovambattista; Aguglia, Umberto

2017-10-01

despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future. Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or 'time-to-event' design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient's ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed. Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients' and clinicians' needs.

Mutual information analysis and detection of interictal morphological differences in interictal epileptiform discharges of patients with partial epilepsies.

PubMed

Varma, N K; Kushwaha, R; Beydoun, A; Williams, W J; Drury, I

1997-10-01

The purpose of this paper is to compare the morphological features of interictal epileptiform discharges (IED) in patients with benign epilepsy of childhood with centrotemporal spikes to IED of those with symptomatic localization related epilepsies using information theory. Three patients from each clinical group were selected. Two-second epochs centered at the peak negativity of the sharp waves were analyzed from a referential montage during stage I sleep. The epochs from the two groups were compared using parametric and information theory analysis. Information analysis determined the likelihood of correctly identifying the clinical group based on the IED. Standard parametric, morphological and spectral analyses were also performed. We found no significant difference in the morphology of the sharp wave between the two groups. The after-going slow wave contained the greatest information that separated the two groups. This result was supported by morphological and spectral differences in the after-going slow wave. Greater distinguishing information is held in the after-going slow wave than the sharp wave for the identification of clinical groups. Information analysis may assist in differentiating clinical syndromes from EEG signals.

Soy infant formula and seizures in children with autism: a retrospective study.

PubMed

Westmark, Cara J

2014-01-01

Seizures are a common phenotype in many neurodevelopmental disorders including fragile X syndrome, Down syndrome and autism. We hypothesized that phytoestrogens in soy-based infant formula were contributing to lower seizure threshold in these disorders. Herein, we evaluated the dependence of seizure incidence on infant formula in a population of autistic children. Medical record data were obtained on 1,949 autistic children from the SFARI Simplex Collection. An autism diagnosis was determined by scores on the ADI-R and ADOS exams. The database included data on infant formula use, seizure incidence, the specific type of seizure exhibited and IQ. Soy-based formula was utilized in 17.5% of the study population. Females comprised 13.4% of the subjects. There was a 2.6-fold higher rate of febrile seizures [4.2% versus 1.6%, OR = 2.6, 95% CI = 1.3-5.3], a 2.1-fold higher rate of epilepsy comorbidity [3.6% versus 1.7%, OR = 2.2, 95% CI = 1.1-4.7] and a 4-fold higher rate of simple partial seizures [1.2% versus 0.3%, OR = 4.8, 95% CI = 1.0-23] in the autistic children fed soy-based formula. No statistically significant associations were found with other outcomes including: IQ, age of seizure onset, infantile spasms and atonic, generalized tonic clonic, absence and complex partial seizures. Limitations of the study included: infant formula and seizure data were based on parental recall, there were significantly less female subjects, and there was lack of data regarding critical confounders such as the reasons the subjects used soy formula, age at which soy formula was initiated and the length of time on soy formula. Despite these limitations, our results suggest that the use of soy-based infant formula may be associated with febrile seizures in both genders and with a diagnosis of epilepsy in males in autistic children. Given the lack of data on critical confounders and the retrospective nature of the study, a prospective study is required to confirm the association.

Familial partial trisomy 15q11-13 presenting as intractable epilepsy in the child and schizophrenia in the mother.

PubMed

Michelson, Marina; Eden, Avi; Vinkler, Chana; Leshinsky-Silver, Esther; Kremer, Uri; Lerman-Sagie, Tally; Lev, Dorit

2011-05-01

Various rearrangements involve the proximal long arm of chromosome 15, including deletions, duplications, translocations, inversions and supernumerary marker chromosome of an inverted duplication. The large marker 15, that contains the Prader-Willi syndrome (PWS)/Angelman syndrome (AS) chromosome region, is usually associated with an abnormal phenotype of moderate to severe mental retardation, seizures, poor motor coordination, early-onset central hypotonia, autism and autistic-like behavior, schizophrenia and mild dysmorphic features. We report a ten year-old girl with normal intelligence prior to the onset of seizures, who developed severe intractable epilepsy at the age of seven years. Family history was significant for a mother with recurrent episodes of acute psychosis. The patient's and mother's karyotype revealed 47,XX+m. Array comparative genomic hybridization (A-CGH) identified a gain of 13 BAC clones from 15q11.2 through 15q13.1, which was then confirmed by FISH to be part of the marker chromosome. This duplicated region contains the SNRPN/UBE3A locus. This case demonstrates that a duplication of 15q11-13 can present differently in the same family either as intractable epilepsy or as a psychiatric illness and that intelligence can be preserved. We suggest that CGH microarray should be performed in cases with intractable epilepsy or schizophrenia, with or without mental retardation. Copyright © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Control of seizures by ketogenic diet-induced modulation of metabolic pathways.

PubMed

Clanton, Ryan M; Wu, Guoyao; Akabani, Gamal; Aramayo, Rodolfo

2017-01-01

Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

Identification of new epilepsy treatments: issues in preclinical methodology.

PubMed

Galanopoulou, Aristea S; Buckmaster, Paul S; Staley, Kevin J; Moshé, Solomon L; Perucca, Emilio; Engel, Jerome; Löscher, Wolfgang; Noebels, Jeffrey L; Pitkänen, Asla; Stables, James; White, H Steve; O'Brien, Terence J; Simonato, Michele

2012-03-01

Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic antiseizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (2) disease-modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, that is, age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Emotional Prosody Processing in Epilepsy: Some Insights on Brain Reorganization.

PubMed

Alba-Ferrara, Lucy; Kochen, Silvia; Hausmann, Markus

2018-01-01

Drug resistant epilepsy is one of the most complex, multifactorial and polygenic neurological syndrome. Besides its dynamicity and variability, it still provides us with a model to study brain-behavior relationship, giving cues on the anatomy and functional representation of brain function. Given that onset zone of focal epileptic seizures often affects different anatomical areas, cortical but limited to one hemisphere, this condition also let us study the functional differences of the left and right cerebral hemispheres. One lateralized function in the human brain is emotional prosody, and it can be a useful ictal sign offering hints on the location of the epileptogenic zone. Besides its importance for effective communication, prosody is not considered an eloquent domain, making resective surgery on its neural correlates feasible. We performed an Electronic databases search (Medline and PsychINFO) from inception to July 2017 for studies about prosody in epilepsy. The search terms included "epilepsy," "seizure," "emotional prosody," and "vocal affect." This review focus on emotional prosody processing in epilepsy as it can give hints regarding plastic functional changes following seizures (preoperatively), resection (post operatively), and also as an ictal sign enabling the assessment of dynamic brain networks. Moreover, it is argued that such reorganization can help to preserve the expression and reception of emotional prosody as a central skill to develop appropriate social interactions.

Identification of new treatments for epilepsy: issues in preclinical methodology

PubMed Central

Galanopoulou, Aristea S.; Buckmaster, Paul S.; Staley, Kevin J.; Moshé, Solomon L.; Perucca, Emilio; Engel, Jerome; Löscher, Wolfgang; Noebels, Jeffrey L.; Pitkänen, Asla; Stables, James; White, Steve H.; O’Brien, Terence J.; Simonato, Michele

2013-01-01

Summary Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (a) new symptomatic anti-seizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (b) disease modifying treatments that prevent or ameliorate the epileptogenic state, and (c) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, i.e. age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical anti-epilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis and comorbidities. PMID:22292566

Paraneoplastic epilepsy.

PubMed

Serafini, Anna; Lukas, Rimas V; VanHaerents, Stephen; Warnke, Peter; Tao, James X; Rose, Sandra; Wu, Shasha

2016-08-01

Epilepsy can be a manifestation of paraneoplastic syndromes which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting other organs and tissues. The antibodies commonly found in paraneoplastic encephalitis can be divided into two main groups depending on the target antigen: 1) antibodies against neuronal cell surface antigens, such as against neurotransmitter (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid (GABA)) receptors, ion channels (voltage-gated potassium channel (VGKC)), and channel-complex proteins (leucine rich, glioma inactivated-1 glycoprotein (LGI1) and contactin-associated protein-2 (CASPR2)) and 2) antibodies against intracellular neuronal antigens (Hu/antineuronal nuclear antibody-1 (ANNA-1), Ma2/Ta, glutamate decarboxylase 65 (GAD65), less frequently to CV2/collapsin response mediator protein 5 (CRMP5)). In this review, we provide a comprehensive survey of the current literature on paraneoplastic epilepsy indexed by the associated onconeuronal antibodies. While a range of seizure types can be seen with paraneoplastic syndromes, temporal lobe epilepsy is the most common because of the association with limbic encephalitis. Early treatment of the paraneoplastic syndrome with immune modulation/suppression may prevent the more serious potential consequences of paraneoplastic epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Low penetrance of autosomal dominant lateral temporal epilepsy in Italian families without LGI1 mutations.

PubMed

Michelucci, Roberto; Pasini, Elena; Malacrida, Sandro; Striano, Pasquale; Bonaventura, Carlo Di; Pulitano, Patrizia; Bisulli, Francesca; Egeo, Gabriella; Santulli, Lia; Sofia, Vito; Gambardella, Antonio; Elia, Maurizio; de Falco, Arturo; Neve, Angela la; Banfi, Paola; Coppola, Giangennaro; Avoni, Patrizia; Binelli, Simona; Boniver, Clementina; Pisano, Tiziana; Marchini, Marco; Dazzo, Emanuela; Fanciulli, Manuela; Bartolini, Yerma; Riguzzi, Patrizia; Volpi, Lilia; de Falco, Fabrizio A; Giallonardo, Anna Teresa; Mecarelli, Oriano; Striano, Salvatore; Tinuper, Paolo; Nobile, Carlo

2013-07-01

In relatively small series, autosomal dominant lateral temporal epilepsy (ADLTE) has been associated with leucine-rich, glioma-inactivated 1 (LGI1) mutations in about 50% of the families, this genetic heterogeneity being probably caused by differences in the clinical characteristics of the families. In this article we report the overall clinical and genetic spectrum of ADLTE in Italy with the aim to provide new insight into its nosology and genetic basis. In a collaborative study of the Commission of Genetics of the Italian League Against Epilepsy (LICE) encompassing a 10-year period (2000-2010), we collected 33 ADLTE families, selected on the basis of the following criteria: presence of at least two members concordant for unprovoked partial seizures with prominent auditory and or aphasic symptoms, absence of any known structural brain pathology or etiology, and normal neurologic examination. The clinical, neurophysiologic, and neuroradiologic findings of all patients were analyzed and a genealogic tree was built for each pedigree. The probands' DNA was tested for LGI1 mutations by direct sequencing and, if negative, were genotyped with single-nucleotide polymorphism (SNP) array to search for disease-linked copy-number variation CNV. The disease penetrance in mutated and nonmutated families was assessed as a proportion of obligate carriers who were affected. The 33 families included a total of 127 affected individuals (61 male, 66 female, 22 deceased). The age at onset ranged between 2 and 60 years (mean 18.7 years). Ninety-one patients (72%) had clear-cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Other symptoms included complex visual hallucinations, vertigo, and déjà vu. Aphasic seizures, associated or not with auditory features, were observed in 20% of the cases, whereas tonic-clonic seizures occurred in 86% of the overall series. Sudden noises could precipitate the seizures in about 20% of cases. Seizures, which usually occurred at a low frequency, were promptly controlled or markedly improved by antiepileptic treatment in the majority of patients. The interictal electroencephalography (EEG) studies showed the epileptiform temporal abnormalities in 62% of cases, with a slight predominance over the left region. Magnetic resonance imaging (MRI) or computerized tomography (CT) scans were negative. LGI1 mutations (missense in nine and a microdeletion in one) were found in only 10 families (30%). The patients belonging to the mutated and not mutated groups did not differ except for penetrance estimate, which was 61.3% and 35% in the two groups, respectively (chi-square, p = 0.017). In addition, the disease risk of members of families with mutations in LGI1 was three times higher than that of members of LGI1-negative families (odds ratio [OR] 2.94, confidence interval [CI] 1.2-7.21). A large number of ADLTE families has been collected over a 10-year period in Italy, showing a typical and homogeneous phenotype. LGI1 mutations have been found in only one third of families, clinically indistinguishable from nonmutated pedigrees. The estimate of penetrance and OR, however, demonstrates a significantly lower penetrance rate and relative disease risk in non-LGI1-mutated families compared with LGI1-mutated pedigrees, suggesting that a complex inheritance pattern may underlie a proportion of these families. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

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.

Dancing with a seizure, a case report.

PubMed

Kim, Keun Tae; Chu, Kon; Lee, Sang Kun

2017-01-25

Dancing is a very rare seizure semiology, and has only few case reports so far. Moreover, no case regarded as dancing with both description and video was presented. A 42-year-old woman with medical intractable epilepsy showed a typical semiology of right temporal lobe epilepsy: right hand automatism and ictal speech. The following semiology, appeared during ictal and post-ictal stage, was complex, rhythmical and sequential movement. It was enough to be called dancing. We hereby report the most plausible dancing in the ictal and post-ictal state, documented by simultaneous video and electroencephalography.

De-novo simple partial status epilepticus presenting as Wernicke's aphasia.

PubMed

Patil, Bhimanagouda; Oware, Agyepong

2012-04-01

Language disturbances manifesting as brief periods of speech arrest occur with seizures originating in the frontal or temporal lobes. These language disturbances are usually present with other features of seizures or may occur in an episodic fashion suggesting their likely epileptic origin. Sustained but reversible aphasia as the sole manifestation of partial status epilepticus is rare, particularly without a history of prior seizures. A few cases have been described in the literature where Broca's or mixed aphasia seems to be more common than Wernicke's aphasia. Here we describe a patient who presented with Wernicke's aphasia secondary to simple partial status epilepticus but without any other features of seizures. The diagnosis was confirmed on EEG and the aphasia reversed after antiepileptic treatment. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Measurement of Local Partial Pressure of Oxygen in the Brain Tissue under Normoxia and Epilepsy with Phosphorescence Lifetime Microscopy

PubMed Central

Zhang, Cong; Bélanger, Samuel; Pouliot, Philippe; Lesage, Frédéric

2015-01-01

In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure. PMID:26305777