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Sample records for absence epilepsy rats

  1. Are rats with genetic absence epilepsy behaviorally impaired?

    PubMed

    Vergnes, M; Marescaux, C; Boehrer, A; Depaulis, A

    1991-07-01

    Absence seizures in humans are characterized by unresponsiveness to external stimuli and inactivity. However, in typical generalized non-convulsive epilepsy in children, intellectual capacities are considered to be normal. Wistar rats from an inbred strain with spontaneous absence-like seizures were compared with rats from the outbred control strain in various behavioral tasks in order to detect possible impairments related either to the absence epilepsy or to occurrence of spike and wave discharges (SWD). Spontaneous circadian locomotion, exploratory activity in an open field, social interactions with an unfamiliar conspecific and mouse killing behavior were similar in both strains. Avoidance learning in a shuttle box or food reinforced learning in a Skinner test were unimpaired or even improved in epileptic rats. During performance of a learned task either in the Skinner box or in a conditioned sound-bar pressing task, SWD were suppressed in epileptic rats as long as they were working for reinforcement. SWD reappeared when the motivation to perform the task had declined: unresponsiveness to a conditioned stimulus was then observed during SWD. These data are in agreement with observations commonly described in children with typical genetic absence epilepsy. PMID:1794357

  2. Levetiracetam in Absence Epilepsy

    ERIC Educational Resources Information Center

    Verrotti, Alberto; Cerminara, Caterina; Domizio, Sergio; Mohn, Angelika; Franzoni, Emilio; Coppola, Giangennaro; Zamponi, Nelia; Parisi, Pasquale; Iannetti, Paola; Curatolo, Paolo

    2008-01-01

    The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty-one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrolment into…

  3. Investigation of ECG Changes in Absence Epilepsy on WAG/Rij Rats

    PubMed Central

    Es'haghi, Fatemeh; Shahabi, Parviz; Frounchi, Javad; Sadighi, Mina; Yousefi, Hadi

    2015-01-01

    Introduction: Seizures are symptoms associated with abnormal electrical activity in electroencephalogram (EEG). The present study was designed to determine the effect of absence seizure on heart rate (HR) changes in electrocardiogram (ECG). Methods: HR alterations were recorded simultaneous with spike and wave discharges (SWD) by EEG in 6 WAG/Rij rats as a well characterized and validated genetic animal epilepsy model. Moreover, 6 control rats were used to distinguish the differences of HR changes between various groups. Electrodes were placed on the skull and under the chest skin, minimizing time delay and signal attenuation. HR was calculated by an adaptable algorithm based on continues wavelet transform (CWT) particular for this study. Three main features of HR; minimum, maximum, and mean values were estimated for pre-ictal and ictal intervals for all seizures. Results: ECG beats detected with sensitivity of 99.9% and positive predictability of 99.8% based on CWT. HR deceleration was found in 86% of the seizures. There were statistically significant (P<0.001) reductions of these values from pre-ictal to ictal intervals. Interictal HR acceleration and ictal deceleration were the major feature of alterations and in 23% of seizures, this decrease had priority to the onsets. Discussion: These findings may lead to design a seizure alarm system based on HR and to obtain new insights about sudden unexpected death in epilepsy (SUDEP) phenomenon and side-effects of antiepileptic drugs (AED). PMID:27307957

  4. On-off intermittency in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy

    SciTech Connect

    Hramov, Alexander; Koronovskii, Alexey A.; Midzyanovskaya, I.S.; Sitnikova, E.; Rijn, C.M. van

    2006-12-15

    In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested.

  5. The genetic absence epilepsy rat from Strasbourg as a model to decipher the neuronal and network mechanisms of generalized idiopathic epilepsies.

    PubMed

    Depaulis, Antoine; David, Olivier; Charpier, Stéphane

    2016-02-15

    First characterized in 1982, the genetic absence epilepsy rat from Strasbourg (GAERS) has emerged as an animal model highly reminiscent of a specific form of idiopathic generalized epilepsy. Both its electrophysiological (spike-and-wave discharges) and behavioral (behavioral arrest) features fit well with those observed in human patients with typical absence epilepsy and required by clinicians for diagnostic purposes. In addition, its sensitivity to antiepileptic drugs closely matches what has been described in the clinic, making this model one of the most predictive. Here, we report how the GAERS, thanks to its spontaneous, highly recurrent and easily recognizable seizures on electroencephalographic recordings, allows to address several key-questions about the pathophysiology and genetics of absence epilepsy. In particular, it offers the unique possibility to explore simultaneously the neural circuits involved in the generation of seizures at different levels of integration, using multiscale methodologies, from intracellular recording to functional magnetic resonance imaging. In addition, it has recently allowed to perform proofs of concept for innovative therapeutic strategies such as responsive deep brain stimulation or synchrotron-generated irradiation based radiosurgery. PMID:26068173

  6. Age-dependent seizures of absence epilepsy and sleep spindles dynamics in WAG/Rij rats

    NASA Astrophysics Data System (ADS)

    Grubov, Vadim V.; Sitnikova, Evgenia Y.; Pavlov, Alexey N.; Khramova, Marina V.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2015-03-01

    In the given paper, a relation between time-frequency characteristics of sleep spindles and the age-dependent epileptic activity in WAG/Rij rats is discussed. Analysis of sleep spindles based on the continuous wavelet transform is performed for rats of different ages. It is shown that the epileptic activity affects the time-frequency intrinsic dynamics of sleep spindles.

  7. Time-frequency dynamics during sleep spindles on the EEG in rodents with a genetic predisposition to absence epilepsy (WAG/Rij rats)

    NASA Astrophysics Data System (ADS)

    Hramov, Alexander E.; Sitnikova, Evgenija Y.; Pavlov, Alexey N.; Grubov, Vadim V.; Koronovskii, Alexey A.; Khramova, Marina V.

    2015-03-01

    Sleep spindles are known to appear spontaneously in the thalamocortical neuronal network of the brain during slow-wave sleep; pathological processes in the thalamocortical network may be the reason of the absence epilepsy. The aim of the present work is to study developed changes in the time-frequency structure of sleep spindles during the progressive development of the absence epilepsy in WAG/Rij rats. EEG recordings were made at age 7 and 9 months. Automatic recognition and subsequent analysis of sleep spindles on the EEG were performed using the continuous wavelet transform. The duration of epileptic discharges and the total duration of epileptic activity were found to increase with age, while the duration of sleep spindles, conversely, decreased. In terms of the mean frequency, sleep spindles could be divided into three classes: `slow' (mean frequency 9.3Hz), `medium' (11.4Hz), and `fast' (13.5Hz). Slow and medium (transitional) spindles in five-month-old animals showed increased frequency from the beginning to the end of the spindle. The more intense the epilepsy is, the shorter are the durations of spindles of all types. The mean frequencies of `medium' and `fast' spindles were higher in rats with more intense signs of epilepsy. Overall, high epileptic activity in WAG/Rij rats was linked with significant changes in spindles of the transitional type, with less marked changes in the two traditionally identified types of spindle, slow and fast.

  8. Antidepressants but not antipsychotics have antiepileptogenic effects with limited effects on comorbid depressive-like behaviour in the WAG/Rij rat model of absence epilepsy

    PubMed Central

    Citraro, Rita; Leo, Antonio; De Fazio, Pasquale; De Sarro, Giovambattista; Russo, Emilio

    2015-01-01

    Background and Purpose Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. Experimental Approach We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behaviour in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6-month-old) rats after a chronic 7 weeks treatment. Key Results ELTT with all antipsychotics did not affect the development of seizures, whereas, both ELTT haloperidol (1 mg·kg−1 day−1) and risperidone (0.5 mg·kg−1 day−1) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30 mg·kg−1 day−1) and duloxetine (10–30 mg·kg−1 day−1) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30 mg·kg−1 day−1 reduced immobility time while at 10 mg·kg−1 day−1 an increase was observed. Conclusions and Implications In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive-like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive-like behaviour. PMID

  9. Childhood Absence Epilepsy: Poor Attention Is More Than Seizures

    MedlinePlus

    ... Spencer, MD Steven Karceski, MD Childhood absence epilepsy Poor attention is more than seizures Liu Lin Thio, ... of this article is prohibited. Childhood absence epilepsy: Poor attention is more than seizures Liu Lin Thio ...

  10. The T-type calcium channel antagonist Z944 rescues impairments in crossmodal and visual recognition memory in Genetic Absence Epilepsy Rats from Strasbourg.

    PubMed

    Marks, Wendie N; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2016-10-01

    Childhood absence epilepsy (CAE) is often comorbid with behavioral and cognitive symptoms, including impaired visual memory. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is an animal model closely resembling CAE; however, cognition in GAERS is poorly understood. Crossmodal object recognition (CMOR) is a recently developed memory task that examines not only purely visual and tactile memory, but also requires rodents to integrate sensory information about objects gained from tactile exploration to enable visual recognition. Both the visual and crossmodal variations of the CMOR task rely on the perirhinal cortex, an area with dense expression of T-type calcium channels. GAERS express a gain-in-function missense mutation in the Cav3.2 T-type calcium channel gene. Therefore, we tested whether the T-type calcium channel blocker Z944 dose dependently (1, 3, 10mg/kg; i.p.) altered CMOR memory in GAERS compared to the non-epileptic control (NEC) strain. GAERS demonstrated recognition memory deficits in the visual and crossmodal variations of the CMOR task that were reversed by the highest dose of Z944. Electroencephalogram recordings determined that deficits in CMOR memory in GAERS were not the result of seizures during task performance. In contrast, NEC showed a decrease in CMOR memory following Z944 treatment. These findings suggest that T-type calcium channels mediate CMOR in both the GAERS and NEC strains. Future research into the therapeutic potential of T-type calcium channel regulation may be particularly fruitful for the treatment of CAE and other disorders characterized by visual memory deficits. PMID:27282256

  11. Evaluation of effects of T and N type calcium channel blockers on the electroencephalogram recordings in Wistar Albino Glaxo/Rij rats, an absence epilepsy model

    PubMed Central

    Durmus, Nedim; Gültürk, Sefa; Kaya, Tijen; Demir, Tuncer; Parlak, Mesut; Altun, Ahmet

    2015-01-01

    Objectives: It is suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges. We aimed to investigate the role of T and N type calcium channels in absence epilepsy experimental model. Materials and Methods: Wistar Albino Glaxo/Rij (WAG/Rij) rats (12–16 weeks old) were randomly allocated into four groups; sham, mibefradil (T type calcium channel blocker), w-Conotoxin MVIIA (N type calcium channel blocker), and mibefradil + w-Conotoxin MVIIA. Beta, alpha, theta, and delta wave ratios of EEG recordings and frequency and duration of spike wave discharges (SWDs) were analyzed and compared between groups. Results: Beta and delta recording ratios in 1 μM/5 μl mibefradil group was significantly different from basal and other dose-injected groups. Beta, alpha, and theta recordings in 0.2 μM/5 μl w-Conotoxin MVIIA group was significantly different from basal and other dose-injected groups. In w-Conotoxin MVIIA after mibefradil group, beta, alpha, and theta recording ratios were significantly different from basal and mibefradil group. Mibefradil and w-Conotoxin MVIIA significantly decreased the frequency and duration of SWDs. The decrease of frequency and duration of SWDs in mibefradil group was significantly different from w-Conotoxin MVIIA group. The frequency and duration of SWDs significantly decreased in w-Conotoxin MVIIA after mibefradil group compared with basal, mibefradil, and w-Conotoxin MVIIA groups. Conclusions: We concluded that both T and L type calcium channels play activator roles in SWDs and have positive effects on frequency and duration of these discharges. These results are related with their central effects more than peripheral effects. PMID:25821308

  12. Altered distribution and function of A2A adenosine receptors in the brain of WAG/Rij rats with genetic absence epilepsy, before and after appearance of the disease.

    PubMed

    D'Alimonte, Iolanda; D'Auro, Mariagrazia; Citraro, Rita; Biagioni, Francesca; Jiang, Shucui; Nargi, Eleonora; Buccella, Silvana; Di Iorio, Patrizia; Giuliani, Patricia; Ballerini, Patrizia; Caciagli, Francesco; Russo, Emilio; De Sarro, Giovambattista; Ciccarelli, Renata

    2009-09-01

    The involvement of excitatory adenosine A(2A) receptors (A(2A)Rs), which probably contribute to the pathophysiology of convulsive seizures, has never been investigated in absence epilepsy. Here, we examined the distribution and function of A(2A)Rs in the brain of Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a model of human absence epilepsy in which disease onset occurs 2-3 months after birth. In the cerebral areas that are mostly involved in the generation of absence seizures (somatosensory cortex, reticular and ventrobasal thalamic nuclei), A(2A)R density was lower in presymptomatic WAG/Rij rats than in control rats, as evaluated by immunohistochemistry and western blotting. Accordingly, in cortical/thalamic slices prepared from the brain of these rats, A(2A)R stimulation with the agonist 2-[4-(-2-carboxyethyl)-phenylamino]-5'-N-ethylcarboxamido-adenosine failed to modulate either cAMP formation, mitogen-activated protein kinase system, or K(+)-evoked glutamate release. In contrast, A(2A)R expression, signalling and function were significantly enhanced in brain slices from epileptic WAG/Rij rats as compared with matched control animals. Additionally, the in vivo injection of the A(2A)R agonist CGS21680, or the antagonist 5-amino-7-(2-phenylethyl)-2-(2-fuyl)-pyrazolo-(4,3-c)1,2,4-triazolo(1,5-c)-pyrimidine, in the examined brain areas of epileptic rats, increased and decreased, respectively, the number/duration of recorded spontaneous spike-wave discharges in a dose-dependent manner during a 1-5 h post-treatment period. Our results support the hypothesis that alteration of excitatory A(2A)R is involved in the pathogenesis of absence seizures and might represent a new interesting target for the therapeutic management of this disease. PMID:19723291

  13. Advances on genetic rat models of epilepsy

    PubMed Central

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  14. Advances on genetic rat models of epilepsy.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  15. Calcium channel antibodies in patients with absence epilepsy.

    PubMed

    Tektürk, Pınar; Baykan, Betül; Ekizoğlu, Esme; Ulusoy, Canan; Aydin-Özemir, Zeynep; Içöz, Sema; Kınay, Demet; Tüzün, Erdem

    2014-07-01

    Autoimmunity has aroused interest in the last years as a contributory mechanism of epilepsy, especially in epilepsies with unknown cause or therapy resistance. Since the relationship of absence epilepsy (AE) with calcium channels is well established, we aimed to investigate related antibodies in patients diagnosed with AE. Consecutive patients with typical absence seizures having either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) with generalized spike and wave discharges on electroencephalography (EEG) were included after their consent. The patients were diagnosed according to the International League Against Epilepsy (ILAE) 2010 criteria. Antibodies against P-Q type voltage gated calcium channels (VGCC) and T-type VGCC subunit Cav3.2 (encoded by the CACNA1H gene) were investigated by RIA and ELISA, respectively. We searched for these antibodies in 32 patients with AE and 53 patients with focal epilepsy of unknown cause (FEOUC) as the disease control group; furthermore, 30 healthy persons served as the healthy controls. Eleven patients (34.3%) with AE had CAE and the remaining patients had JAE. Only a 47-year-old female FEOUC patient, who also had systemic lupus erythematosus with normal MRI scans showed antibodies against P-Q type VGCC, whereas no antibody positivity could be found in other FEOUC and AE patients and healthy controls. Our results might suggest that calcium channel antibodies do not play an important role in the pathophysiology of AE. Further studies with larger groups of other epileptic syndromes are needed to confirm our results. PMID:24147594

  16. Enhanced tonic GABAA inhibition in typical absence epilepsy

    PubMed Central

    Cope, David W.; Di Giovanni, Giuseppe; Fyson, Sarah J.; Orbán, Gergely; Errington, Adam C.; Lőrincz, Magor L.; Gould, Timothy M.; Carter, David A.; Crunelli, Vincenzo

    2010-01-01

    The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy. PMID:19966779

  17. Analysis of rare copy number variation in absence epilepsies

    PubMed Central

    Rosch, Richard E.; Valentin, Antonio; Makoff, Andrew; Robinson, Robert; Everett, Kate V.; Nashef, Lina; Pal, Deb K.

    2016-01-01

    Objective: To identify shared genes and pathways between common absence epilepsy (AE) subtypes (childhood absence epilepsy [CAE], juvenile absence epilepsy [JAE], and unclassified absence epilepsy [UAE]) that may indicate common mechanisms for absence seizure generation and potentially a diagnostic continuum. Methods: We used high-density single-nucleotide polymorphism arrays to analyze genome-wide rare copy number variation (CNV) in a cohort of 144 children with AEs (95 CAE, 26 UAE, and 23 JAE). Results: We identified CNVs that are known risk factors for AE in 4 patients, including 3x 15q11.2 deletion. We also expanded the phenotype at 4 regions more commonly identified in other neurodevelopmental disorders: 1p36.33 duplication, 1q21.1 deletion, 22q11.2 duplication, and Xp22.31 deletion and duplication. Fifteen patients (10.5%) were found to carry rare CNVs that disrupt genes associated with neuronal development and function (8 CAE, 2 JAE, and 5 UAE). Four categories of protein are each disrupted by several CNVs: (1) synaptic vesicle membrane or vesicle endocytosis, (2) synaptic cell adhesion, (3) synapse organization and motility via actin, and (4) gap junctions. CNVs within these categories are shared across the AE subtypes. Conclusions: Our results have reinforced the complex and heterogeneous nature of the AEs and their potential for shared genetic mechanisms and have highlighted several pathways that may be important in epileptogenesis of absence seizures. PMID:27123475

  18. Cortical and subcortical brain alterations in Juvenile Absence Epilepsy.

    PubMed

    Tondelli, Manuela; Vaudano, Anna Elisabetta; Ruggieri, Andrea; Meletti, Stefano

    2016-01-01

    Despite the common assumption that genetic generalized epilepsies are characterized by a macroscopically normal brain on magnetic resonance imaging, subtle structural brain alterations have been detected by advanced neuroimaging techniques in Childhood Absence Epilepsy syndrome. We applied quantitative structural MRI analysis to a group of adolescents and adults with Juvenile Absence Epilepsy (JAE) in order to investigate micro-structural brain changes using different brain measures. We examined grey matter volumes, cortical thickness, surface areas, and subcortical volumes in 24 patients with JAE compared to 24 healthy controls; whole-brain voxel-based morphometry (VBM) and Freesurfer analyses were used. When compared to healthy controls, patients revealed both grey matter volume and surface area reduction in bilateral frontal regions, anterior cingulate, and right mesial-temporal lobe. Correlation analysis with disease duration showed that longer disease was correlated with reduced surface area in right pre- and post-central gyrus. A possible effect of valproate treatment on brain structures was excluded. Our results indicate that subtle structural brain changes are detectable in JAE and are mainly located in anterior nodes of regions known to be crucial for awareness, attention and memory. PMID:27551668

  19. Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release.

    PubMed

    Russo, Emilio; Andreozzi, Francesco; Iuliano, Rodolfo; Dattilo, Vincenzo; Procopio, Teresa; Fiume, Giuseppe; Mimmi, Selena; Perrotti, Nicola; Citraro, Rita; Sesti, Giorgio; Constanti, Andrew; De Sarro, Giovambattista

    2014-11-01

    The mammalian target of rapamycin (mTOR) pathway has been recently indicated as a suitable drug target for the prevention of epileptogenesis. The mTOR pathway is known for its involvement in the control of the immune system. Since neuroinflammation is recognized as a major contributor to epileptogenesis, we wished to examine whether the neuroprotective effects of mTOR modulation could involve a suppression of the neuroinflammatory process in epileptic brain. We have investigated the early molecular mechanisms involved in the effects of intracerebral administration of the lipopolysaccharide (LPS) in the WAG/Rij rat model of absence epilepsy, in relation to seizure generation and depressive-like behavior; we also tested whether the effects of LPS could be modulated by treatment with rapamycin (RAP), a specific mTOR inhibitor. We determined, in specific rat brain areas, levels of p-mTOR/p-p70S6K and also p-AKT/p-AMPK as downstream or upstream indicators of mTOR activity and tested the effects of LPS and RAP co-administration. Changes in the brain levels of pro-inflammatory cytokines IL-1β and TNF-α and their relative mRNA expression levels were measured, and the involvement of nuclear factor-κB (NF-κB) was also examined in vitro. We confirmed that RAP inhibits the aggravation of absence seizures and depressive-like/sickness behavior induced by LPS in the WAG/Rij rats through the activation of mTOR and show that this effect is correlated with the ability of RAP to dampen and delay LPS increases in neuroinflammatory cytokines IL-1β and TNF-α, most likely through inhibition of the activation of NF-κB. Our results suggest that such a mechanism could contribute to the antiseizure, antiepileptogenic and behavioral effects of RAP and further highlight the potential therapeutic usefulness of mTOR inhibition in the management of human epilepsy and other neurological disorders. Furthermore, we show that LPS-dependent neuroinflammatory effects are also mediated by a

  20. Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures

    PubMed Central

    Bazyan, A. S.; van Luijtelaar, G.

    2013-01-01

    The absence epilepsy typical electroencephalographic pattern of sharp spikes and slow waves (SWDs) is considered to be due to an interaction of an initiation site in the cortex and a resonant circuit in the thalamus. The hyperpolarization-activated cyclic nucleotide-gated cationic Ih pacemaker channels (HCN) play an important role in the enhanced cortical excitability. The role of thalamic HCN in SWD occurrence is less clear. Absence epilepsy in the WAG/Rij strain is accompanied by deficiency of the activity of dopaminergic system, which weakens the formation of an emotional positive state, causes depression-like symptoms, and counteracts learning and memory processes. It also enhances GABAA receptor activity in the striatum, globus pallidus, and reticular thalamic nucleus, causing a rise of SWD activity in the cortico-thalamo-cortical networks. One of the reasons for the occurrence of absences is that several genes coding of GABAA receptors are mutated. The question arises: what the role of DA receptors is. Two mechanisms that cause an infringement of the function of DA receptors in this genetic absence epilepsy model are proposed. PMID:23738145

  1. Are Absence Epilepsy and Nocturnal Frontal Lobe Epilepsy System Epilepsies of the Sleep/Wake System?

    PubMed Central

    Halász, Péter

    2015-01-01

    System epilepsy is an emerging concept interpreting major nonlesional epilepsies as epileptic dysfunctions of physiological systems. I extend here the concept of reflex epilepsy to epilepsies linked to input dependent physiological systems. Experimental and clinical reseach data were collected to create a coherent explanation of underlying pathomechanism in AE and NFLE. We propose that AE should be interpreted as epilepsy linked to the corticothalamic burst-firing mode of NREM sleep, released by evoked vigilance level oscillations characterized by reactive slow wave response. In the genetic variation of NFLE the ascending cholinergic arousal system plays an essential role being in strong relationship with a gain mutation of the nicotinic acethylcholin receptors, rendering the arousal system hyperexcitable. I try to provide a more unitary interpretation for the variable seizure manifestation integrating them as different degree of pathological arosuals and alarm reactions. As a supporting hypothesis the similarity between arousal parasomnias and FNLE is shown, underpinned by overlaping pathomechanism and shared familiarity, but without epileptic features. Lastly we propose that both AE and NFLE are system epilepsies of the sleep-wake system representing epileptic disorders of the antagonistic sleep/arousal network. This interpretation may throw new light on the pathomechanism of AE and NFLE. PMID:26175547

  2. Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy

    PubMed Central

    Glauser, Tracy A.; Cnaan, Avital; Shinnar, Shlomo; Hirtz, Deborah G.; Dlugos, Dennis; Masur, David; Clark, Peggy O.; Capparelli, Edmund V.; Adamson, Peter C.

    2010-01-01

    BACKGROUND Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined. METHODS In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons. RESULTS The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P = 0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P = 0.03). CONCLUSIONS Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with

  3. Therapeutic Outcomes and Prognostic Factors in Childhood Absence Epilepsy

    PubMed Central

    Kim, Hye Ryun; Kim, Gun-Ha; Eun, So-Hee; Eun, Baik-Lin

    2016-01-01

    Background and Purpose Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis. Methods Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings. Results The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response. Conclusions This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy. PMID:26610892

  4. Abnormal cortical thickness connectivity persists in childhood absence epilepsy

    PubMed Central

    Curwood, Evan K; Pedersen, Mangor; Carney, Patrick W; Berg, Anne T; Abbott, David F; Jackson, Graeme D

    2015-01-01

    Objective Childhood absence epilepsy (CAE) is a childhood-onset generalized epilepsy. Recent fMRI studies have suggested that frontal cortex activity occurs before thalamic involvement in epileptic discharges suggesting that frontal cortex may play an important role in childhood absence seizures. Neurocognitive deficits can persist after resolution of the epilepsy. We investigate whether structural connectivity changes are present in the brains of CAE patients in young adulthood. Methods Cortical thickness measurements were obtained for 30 subjects with CAE (mean age 21 ± 2 years) and 56 healthy controls (mean age 24 ± 4) and regressed for age, sex, and total intracranial volume (TIV). Structural connectivity was evaluated by measuring the correlation between average cortical thicknesses in 915 regions over the brain. Maps of connectivity strength were then obtained for both groups. Results When compared to controls, the CAE group shows overall increased “connectivity” with focal increased connection strength in anterior regions including; the anterior cingulate and the insula and superior temporal gyrus bilaterally; the right orbito-frontal and supramarginal regions; and the left entorhinal cortex. Decreased connection strength in the CAE group was found in the left occipital lobe, with a similar trend in right occipital lobe. Interpretation Brains in young adults whose CAE was resolved had abnormal structural connectivity. Our findings suggest that frontal regions correlate most with cortical thickness throughout the brain in CAE patients, whereas occipital regions correlate most in well matched normal controls. We interpret this as evidence of a developmental difference in CAE that emphasizes these frontal lobe regions, perhaps driven by frontal lobe epileptiform activity. PMID:26000319

  5. Mixed myoclonic-absence status epilepticus in juvenile myoclonic epilepsy.

    PubMed

    Gélisse, Philippe; Crespel, Arielle

    2015-03-01

    Myoclonic status epilepticus or mixed absence-myoclonic status is uncommon in juvenile myoclonic epilepsy (JME), often precipitated by sleep deprivation, withdrawal of medication, or inadequate antiepileptic drugs (Thomas et al., 2006; Crespel et al., 2013). Such episodes respond well to benzodiazepines or valproate (Crespel et al., 2013). We present the video-EEG of a 24-year-old woman with JME and bipolar disorder. She had a confusional state five days after withdrawal of clonazepam (14 mg/d) and introduction of oxazepam (200 mg/d), followed by catatonic stupor with subtle myoclonus of the face and the arms. The EEG showed absence status (figures 1, 2), which stopped after IV injection of clonazepam (1 mg) (figure 3). Consciousness returned to normal [Published with video sequence and figures (1)]. PMID:25644293

  6. The WAG/Rij strain: a genetic animal model of absence epilepsy with comorbidity of depression [corrected].

    PubMed

    Sarkisova, Karine; van Luijtelaar, Gilles

    2011-06-01

    A great number of clinical observations show a relationship between epilepsy and depression. Idiopathic generalized epilepsy, including absence epilepsy, has a genetic basis. The review provides evidence that WAG/Rij rats can be regarded as a valid genetic animal model of absence epilepsy with comorbidity of depression. WAG/Rij rats, originally developed as an animal model of human absence epilepsy, share many EEG and behavioral characteristics resembling absence epilepsy in humans, including the similarity of action of various antiepileptic drugs. Behavioral studies indicate that WAG/Rij rats exhibit depression-like symptoms: decreased investigative activity in the open field test, increased immobility in the forced swimming test, and decreased sucrose consumption and preference (anhedonia). In addition, WAG/Rij rats adopt passive strategies in stressful situations, express some cognitive disturbances (reduced long-term memory), helplessness, and submissiveness, inability to make choice and overcome obstacles, which are typical for depressed patients. Elevated anxiety is not a characteristic (specific) feature of WAG/Rij rats; it is a characteristic for only a sub-strain of WAG/Rij rats susceptible to audiogenic seizures. Interestingly, WAG/Rij rats display a hyper-response to amphetamine similar to anhedonic depressed patients. WAG/Rij rats are sensitive only to chronic, but not acute, antidepressant treatments, suggesting that WAG/Rij rats fulfill a criterion of predictive validity for a putative animal model of depression. However, more and different antidepressant drugs still await evaluation. Depression-like behavioral symptoms in WAG/Rij rats are evident at baseline conditions, not exclusively after stress. Experiments with foot-shock stress do not point towards higher stress sensitivity at both behavioral and hormonal levels. However, freezing behavior (coping deficits) and blunted response of 5HT in the frontal cortex to uncontrollable sound stress

  7. Altered resting state functional network connectivity in children absence epilepsy.

    PubMed

    Li, Qifu; Cao, Weifang; Liao, Xiaoping; Chen, Zhibin; Yang, Tianhua; Gong, Qiyong; Zhou, Dong; Luo, Cheng; Yao, Dezhong

    2015-07-15

    Altered functional connectivity has been associated with the influence of epileptic activity. Abnormalities in connectivity, particularly in dorsal attention (DAN), salience (SN) and default mode (DMN) networks, might contribute to the loss of consciousness during seizures and cognitive deficits in patients with children absence epilepsy (CAE). The objective of the present study was to identify whether the functional network connectivity (FNC) is changed between patients with CAE and healthy controls. Using independent component analysis, twelve resting state networks (RSNs) were identified in resting state functional magnetic resonance imaging data sets in eighteen CAE patients and twenty-one healthy controls. Analyses of the group differences in FNC strength were conducted, controlling for age and gender effects. The findings showed that some functional networks were clustered into two subgroups, correlated within subgroups and antagonized with each other. Compared with the controls, patients with CAE demonstrated abnormal FNC strength among three networks: DMN, DAN and SN. In addition, the antagonism of two subgroups was altered. These results might reflect the underlying neuronal functional impairment or altered integration among these RSNs in CAE, suggesting that the abnormal functional connectivity is likely to imply the pathological mechanism associated with the accumulative influence of epileptic activity. These findings contribute to the understanding of the behavior abnormality in CAE, such as disturbed executive and attentional functions and the loss of consciousness during absence seizures. PMID:25982500

  8. Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies.

    PubMed

    Yalçın, Ozlem

    2012-03-01

    Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants. PMID:22206818

  9. Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?

    PubMed Central

    van Luijtelaar, Gilles; Onat, Filiz Yilmaz; Gallagher, Martin J.

    2014-01-01

    While epidemiological data suggest a female prevalence in human childhood- and adolescence-onset typical absence epilepsy syndromes, the sex difference is less clear in adult-onset syndromes. In addition, although there are more females than males diagnosed with typical absence epilepsy syndromes, there is a paucity of studies on sex differences in seizure frequency and semiology in patients diagnosed with any absence epilepsy syndrome. Moreover, it is unknown if there are sex differences in the prevalence or expression of atypical absence epilepsy syndromes. Surprisingly, most studies of animal models of absence epilepsy either did not investigate sex differences, or failed to find sex-dependent effects. However, various rodent models for atypical syndromes such as the AY9944 model (prepubertal females show a higher incidence than prepubertal males), BN model also with a higher prevalence in males and the Gabra1 deletion mouse in the C57BL/6J strain offer unique possibilities for the investigation of the mechanisms involved in sex differences. Although the mechanistic bases for the sex differences in humans or these three models are not yet known, studies of the effects of sex hormones on seizures have offered some possibilities. The sex hormones progesterone, estradiol and testosterone exert diametrically opposite effects in genetic absence epilepsy and pharmacologically-evoked convulsive types of epilepsy models. In addition, acute pharmacological effects of progesterone on absence seizures during proestrus are opposite to those seen during pregnancy. 17β-Estradiol has anti-absence seizure effects, but it is only active in atypical absence models. It is speculated that the pro-absence action of progesterone, and perhaps also the delayed pro-absence action of testosterone, are mediated through the neurosteroid allopregnanolone and its structural and functional homolog, androstanediol. These two steroids increase extrasynaptic thalamic tonic GABAergic inhibition

  10. Animal models of absence epilepsies: what do they model and do sex and sex hormones matter?

    PubMed

    van Luijtelaar, Gilles; Onat, Filiz Yilmaz; Gallagher, Martin J

    2014-12-01

    While epidemiological data suggest a female prevalence in human childhood- and adolescence-onset typical absence epilepsy syndromes, the sex difference is less clear in adult-onset syndromes. In addition, although there are more females than males diagnosed with typical absence epilepsy syndromes, there is a paucity of studies on sex differences in seizure frequency and semiology in patients diagnosed with any absence epilepsy syndrome. Moreover, it is unknown if there are sex differences in the prevalence or expression of atypical absence epilepsy syndromes. Surprisingly, most studies of animal models of absence epilepsy either did not investigate sex differences, or failed to find sex-dependent effects. However, various rodent models for atypical syndromes such as the AY9944 model (prepubertal females show a higher incidence than prepubertal males), BN model (also with a higher prevalence in males) and the Gabra1 deletion mouse in the C57BL/6J strain offer unique possibilities for the investigation of the mechanisms involved in sex differences. Although the mechanistic bases for the sex differences in humans or these three models are not yet known, studies of the effects of sex hormones on seizures have offered some possibilities. The sex hormones progesterone, estradiol and testosterone exert diametrically opposite effects in genetic absence epilepsy and pharmacologically-evoked convulsive types of epilepsy models. In addition, acute pharmacological effects of progesterone on absence seizures during proestrus are opposite to those seen during pregnancy. 17β-Estradiol has anti-absence seizure effects, but it is only active in atypical absence models. It is speculated that the pro-absence action of progesterone, and perhaps also the delayed pro-absence action of testosterone, are mediated through the neurosteroid allopregnanolone and its structural and functional homolog, androstanediol. These two steroids increase extrasynaptic thalamic tonic GABAergic

  11. Unilateral and Bilateral Cortical Resection: Effects on Spike-Wave Discharges in a Genetic Absence Epilepsy Model

    PubMed Central

    Scicchitano, Francesca; van Rijn, Clementina M.; van Luijtelaar, Gilles

    2015-01-01

    Research Question Recent discoveries have challenged the traditional view that the thalamus is the primary source driving spike-and-wave discharges (SWDs). At odds, SWDs in genetic absence models have a cortical focal origin in the deep layers of the perioral region of the somatosensory cortex. The present study examines the effect of unilateral and bilateral surgical resection of the assumed focal cortical region on the occurrence of SWDs in anesthetized WAG/Rij rats, a well described and validated genetic absence model. Methods Male WAG/Rij rats were used: 9 in the resected and 6 in the control group. EEG recordings were made before and after craniectomy, after unilateral and after bilateral removal of the focal region. Results SWDs decreased after unilateral cortical resection, while SWDs were no longer noticed after bilateral resection. This was also the case when the resected areas were restricted to layers I-IV with layers V and VI intact. Conclusions These results suggest that SWDs are completely abolished after bilateral removal of the focal region, most likely by interference with an intracortical columnar circuit. The evidence suggests that absence epilepsy is a network type of epilepsy since interference with only the local cortical network abolishes all seizures. PMID:26262879

  12. The role of perioral afferentation in the occurrenceof spike-wave discharges in the WAG/Rij modelof absence epilepsy.

    PubMed

    Abbasova, K R; Chepurnov, S A; Chepurnova, N E; van Luijtelaar, G

    2010-12-17

    According to the focal cortical theory of absence epilepsy, spike-and-wave discharges (SWDs) have a cortical focal origin in the perioral region of the somatosensory cortex in rats. In the present study the role of peripheral afferents of the perioral (snout) region in the occurrence of spontaneous SWDs was investigated in the WAG/Rij (Wistar Albino Glaxo from Rijswijk) rat model of absence epilepsy in order to examine whether an input from peripheral sources is imperative for the occurrence of SWDs. Twelve male WAG/Rij rats were chronically equipped with cortical EEG electrodes. Peripheral afferents of the perioral region of the snout nervus trigeminus were pharmacologically blocked with a local injection of 2% Novocain, a blockade of nervus facialis and saline injections were used as controls. ECoGs were recorded before and after bilateral injection of the drug. Blockade of the n. trigeminus decreased the incidence and duration of SWD, while similar injections with Novocain near the n. facialis had no effect. Injections with saline were also not effective. Our data demonstrate that intact peripheral afferent input may be primarily involved in the initiation of SWDs. It suggests that the cortico-thalamo-cortical circuits need the peripheral stimulations from the snout and vibrissae for an initiation of the spontaneous SWDs. PMID:20934415

  13. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy.

    PubMed

    Wang, Guangfu; Bochorishvili, Genrieta; Chen, Yucai; Salvati, Kathryn A; Zhang, Peng; Dubel, Steve J; Perez-Reyes, Edward; Snutch, Terrance P; Stornetta, Ruth L; Deisseroth, Karl; Erisir, Alev; Todorovic, Slobodan M; Luo, Jian-Hong; Kapur, Jaideep; Beenhakker, Mark P; Zhu, J Julius

    2015-07-15

    CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily incorporate into synapses, replace existing CaV3.2 channels, and can induce local calcium influx to control NMDA transmission strength in an activity-dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked hCaV3.2(C456S) mutant channels have a higher channel open probability, induce more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave discharges and absence-like epilepsy characteristic of CAE patients, which can be suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel antagonists. These results reveal an unexpected role of CaV3.2 channels in regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for human CAE. PMID:26220996

  14. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

    PubMed Central

    Wang, Guangfu; Bochorishvili, Genrieta; Chen, Yucai; Salvati, Kathryn A.; Zhang, Peng; Dubel, Steve J.; Perez-Reyes, Edward; Snutch, Terrance P.; Stornetta, Ruth L.; Deisseroth, Karl; Erisir, Alev; Todorovic, Slobodan M.; Luo, Jian-Hong; Kapur, Jaideep; Beenhakker, Mark P.; Zhu, J. Julius

    2015-01-01

    CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily incorporate into synapses, replace existing CaV3.2 channels, and can induce local calcium influx to control NMDA transmission strength in an activity-dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked hCaV3.2(C456S) mutant channels have a higher channel open probability, induce more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave discharges and absence-like epilepsy characteristic of CAE patients, which can be suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel antagonists. These results reveal an unexpected role of CaV3.2 channels in regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for human CAE. PMID:26220996

  15. Quantitative EEG analysis of the maturational changes associated with childhood absence epilepsy

    NASA Astrophysics Data System (ADS)

    Rosso, O. A.; Hyslop, W.; Gerlach, R.; Smith, R. L. L.; Rostas, J. A. P.; Hunter, M.

    2005-10-01

    This study aimed to examine the background electroencephalography (EEG) in children with childhood absence epilepsy, a condition whose presentation has strong developmental links. EEG hallmarks of absence seizure activity are widely accepted and there is recognition that the bulk of inter-ictal EEG in this group is normal to the naked eye. This multidisciplinary study aimed to use the normalized total wavelet entropy (NTWS) (Signal Processing 83 (2003) 1275) to examine the background EEG of those patients demonstrating absence seizure activity, and compare it with children without absence epilepsy. This calculation can be used to define the degree of order in a system, with higher levels of entropy indicating a more disordered (chaotic) system. Results were subjected to further statistical analyses of significance. Entropy values were calculated for patients versus controls. For all channels combined, patients with absence epilepsy showed (statistically significant) lower entropy values than controls. The size of the difference in entropy values was not uniform, with certain EEG electrodes consistently showing greater differences than others.

  16. Complexity of Multi-Channel Electroencephalogram Signal Analysis in Childhood Absence Epilepsy

    PubMed Central

    Chang, Chi-Feng; Lu, Wen-Yu; Lin, Chun-Yen; Lee, Wang-Tso; Shieh, Jiann-Shing

    2015-01-01

    Absence epilepsy is an important epileptic syndrome in children. Multiscale entropy (MSE), an entropy-based method to measure dynamic complexity at multiple temporal scales, is helpful to disclose the information of brain connectivity. This study investigated the complexity of electroencephalogram (EEG) signals using MSE in children with absence epilepsy. In this research, EEG signals from 19 channels of the entire brain in 21 children aged 5-12 years with absence epilepsy were analyzed. The EEG signals of pre-ictal (before seizure) and ictal states (during seizure) were analyzed by sample entropy (SamEn) and MSE methods. Variations of complexity index (CI), which was calculated from MSE, from the pre-ictal to the ictal states were also analyzed. The entropy values in the pre-ictal state were significantly higher than those in the ictal state. The MSE revealed more differences in analysis compared to the SamEn. The occurrence of absence seizures decreased the CI in all channels. Changes in CI were also significantly greater in the frontal and central parts of the brain, indicating fronto-central cortical involvement of “cortico-thalamo-cortical network” in the occurrence of generalized spike and wave discharges during absence seizures. Moreover, higher sampling frequency was more sensitive in detecting functional changes in the ictal state. There was significantly higher correlation in ictal states in the same patient in different seizures but there were great differences in CI among different patients, indicating that CI changes were consistent in different absence seizures in the same patient but not from patient to patient. This implies that the brain stays in a homogeneous activation state during the absence seizures. In conclusion, MSE analysis is better than SamEn analysis to analyze complexity of EEG, and CI can be used to investigate the functional brain changes during absence seizures. PMID:26244497

  17. Complexity of Multi-Channel Electroencephalogram Signal Analysis in Childhood Absence Epilepsy.

    PubMed

    Weng, Wen-Chin; Jiang, George J A; Chang, Chi-Feng; Lu, Wen-Yu; Lin, Chun-Yen; Lee, Wang-Tso; Shieh, Jiann-Shing

    2015-01-01

    Absence epilepsy is an important epileptic syndrome in children. Multiscale entropy (MSE), an entropy-based method to measure dynamic complexity at multiple temporal scales, is helpful to disclose the information of brain connectivity. This study investigated the complexity of electroencephalogram (EEG) signals using MSE in children with absence epilepsy. In this research, EEG signals from 19 channels of the entire brain in 21 children aged 5-12 years with absence epilepsy were analyzed. The EEG signals of pre-ictal (before seizure) and ictal states (during seizure) were analyzed by sample entropy (SamEn) and MSE methods. Variations of complexity index (CI), which was calculated from MSE, from the pre-ictal to the ictal states were also analyzed. The entropy values in the pre-ictal state were significantly higher than those in the ictal state. The MSE revealed more differences in analysis compared to the SamEn. The occurrence of absence seizures decreased the CI in all channels. Changes in CI were also significantly greater in the frontal and central parts of the brain, indicating fronto-central cortical involvement of "cortico-thalamo-cortical network" in the occurrence of generalized spike and wave discharges during absence seizures. Moreover, higher sampling frequency was more sensitive in detecting functional changes in the ictal state. There was significantly higher correlation in ictal states in the same patient in different seizures but there were great differences in CI among different patients, indicating that CI changes were consistent in different absence seizures in the same patient but not from patient to patient. This implies that the brain stays in a homogeneous activation state during the absence seizures. In conclusion, MSE analysis is better than SamEn analysis to analyze complexity of EEG, and CI can be used to investigate the functional brain changes during absence seizures. PMID:26244497

  18. Epilepsy

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Epilepsy KidsHealth > For Kids > Epilepsy Print A A A ... With Epilepsy Different? en español Epilepsia What Is Epilepsy? Epilepsy comes from a Greek word meaning "to ...

  19. Viscum Album in the Treatment of a Girl With Refractory Childhood Absence Epilepsy.

    PubMed

    von Schoen-Angerer, Tido; Madeleyn, René; Kienle, Gunver; Kiene, Helmut; Vagedes, Jan

    2015-07-01

    Viscum album (European mistletoe) extracts have known immunomodulatory effects but little data exist on anticonvulsant activity despite its usefulness having been reported for centuries. A 4½-year-old girl with childhood absence epilepsy and global developmental delay was treated with different antiepileptic drugs and ketogenic diet but failed to become seizure free over a 2-year period. She also received different herbal remedies as part of an integrative medicine approach. Initial improvement occurred on valproate-ethosuximide, a further improvement was seen after adding clobazam to valproate. Final cessation of absence activity occurred after a dose increase of V album. She was still seizure free at the 12-month follow-up. V album appears to have been a necessary adjunct treatment for this child to become seizure free. We call on physicians to report their experiences of V album in epilepsy and suggest further study. PMID:25038133

  20. Genetics of complex neurological disease: challenges and opportunities for modeling epilepsy in mice and rats.

    PubMed

    Frankel, Wayne N

    2009-08-01

    Currently, approximately 20 genetic variants are known to cause Mendelian forms of human epilepsy, leaving a vast heritability undefined. Rodent models for genetically complex epilepsy have been studied for many years, but only recently have strong candidate genes emerged, including Cacna1 g in the GAERS rat model of absence epilepsy and Kcnj10 in the low seizure threshold of DBA/2 mice. In parallel, a growing number of mouse mutations studied on multiple strain backgrounds reveal the impact of genetic modifiers on seizure severity, incidence or form--perhaps mimicking the complexity seen in humans. The field of experimental genetics in rodents is poised to study discrete epilepsy mutations on a diverse choice of strain backgrounds to develop better models and identify modifiers. But, it must find the right balance between embracing the strain diversity available, with the ability to detect and characterize genetic effects. Using alternative strain backgrounds when studying epilepsy mutations will enhance the modeling of epilepsy as a complex genetic disease. PMID:19665252

  1. Epilepsy

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Epilepsy KidsHealth > For Teens > Epilepsy Print A A A ... embarrass himself or scare his friends. What Is Epilepsy? Epilepsy is a condition of the nervous system ...

  2. Epilepsy

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Epilepsy Information Page Clinical Trials Epilepsy Surgery This study ... en Español Additional resources from MedlinePlus What is Epilepsy? The epilepsies are a spectrum of brain disorders ...

  3. Altered Intrathalamic GABAA Neurotransmission in a Mouse Model of a Human Genetic Absence Epilepsy Syndrome

    PubMed Central

    Zhou, Chengwen; Ding, Li; Deel, M. Elizabeth; Ferrick, Elizabeth A.; Emeson, Ronald B.; Gallagher, Martin J.

    2014-01-01

    We previously demonstrated that heterozygous deletion of Gabra1, the mouse homolog of the human absence epilepsy gene that encodes the GABAA receptor (GABAAR) α1 subunit, causes absence seizures. We showed that cortex partially compensates for this deletion by increasing the cell surface expression of residual α1 subunit and by increasing α3 subunit expression. Absence seizures also involve two thalamic nuclei: the ventrobasal (VB) nucleus, which expresses only the α1 and α4 subtypes of GABAAR α subunits, and the reticular (nRT) nucleus, which expresses only the α3 subunit subtype. Here, we found that, unlike cortex, VB exhibited significantly reduced total and synaptic α1 subunit expression. In addition, heterozygous α1 subunit deletion substantially reduced miniature inhibitory postsynaptic current (mIPSC) peak amplitudes and frequency in VB. However, there was no change in expression of the extrasynaptic α4 or δ subunits in VB and, unlike other models of absence epilepsy, no change in tonic GABAAR currents. Although heterozygous α1 subunit knockout increased α3 subunit expression in medial thalamic nuclei, it did not alter α3 subunit expression in nRT. However, it did enlarge the presynaptic vesicular inhibitory amino acid transporter puncta and lengthen the time constant of mIPSC decay in nRT. We conclude that increased tonic GABAA currents are not necessary for absence seizures. In addition, heterozygous loss of α1 subunit disinhibits VB by substantially reducing phasic GABAergic currents and surprisingly, it also increases nRT inhibition by prolonging phasic currents. The increased inhibition in nRT likely represents a partial compensation that helps reduce absence seizures. PMID:25447232

  4. Altered intrathalamic GABAA neurotransmission in a mouse model of a human genetic absence epilepsy syndrome.

    PubMed

    Zhou, Chengwen; Ding, Li; Deel, M Elizabeth; Ferrick, Elizabeth A; Emeson, Ronald B; Gallagher, Martin J

    2015-01-01

    We previously demonstrated that heterozygous deletion of Gabra1, the mouse homolog of the human absence epilepsy gene that encodes the GABAA receptor (GABAAR) α1 subunit, causes absence seizures. We showed that cortex partially compensates for this deletion by increasing the cell surface expression of residual α1 subunit and by increasing α3 subunit expression. Absence seizures also involve two thalamic nuclei: the ventrobasal (VB) nucleus, which expresses only the α1 and α4 subtypes of GABAAR α subunits, and the reticular (nRT) nucleus, which expresses only the α3 subunit subtype. Here, we found that, unlike cortex, VB exhibited significantly reduced total and synaptic α1 subunit expression. In addition, heterozygous α1 subunit deletion substantially reduced miniature inhibitory postsynaptic current (mIPSC) peak amplitudes and frequency in VB. However, there was no change in the expression of the extrasynaptic α4 or δ subunits in VB and, unlike other models of absence epilepsy, no change in tonic GABAAR currents. Although heterozygous α1 subunit knockout increased α3 subunit expression in medial thalamic nuclei, it did not alter α3 subunit expression in nRT. However, it did enlarge the presynaptic vesicular inhibitory amino acid transporter puncta and lengthen the time constant of mIPSC decay in nRT. We conclude that increased tonic GABAA currents are not necessary for absence seizures. In addition, heterozygous loss of α1 subunit disinhibits VB by substantially reducing phasic GABAergic currents and surprisingly, it also increases nRT inhibition by prolonging phasic currents. The increased inhibition in nRT likely represents a partial compensation that helps reduce absence seizures. PMID:25447232

  5. Epilepsy

    SciTech Connect

    Fisher, R.S.; Frost, J.J. )

    1991-04-01

    As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18(F)FDG in some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18(F)FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.95 references.

  6. Epileptic activity during early postnatal life in the AY-9944 model of atypical absence epilepsy.

    PubMed

    Jung, Seungmoon; Jeong, Yong; Jeon, Daejong

    2015-05-01

    Atypical absence epilepsy (AAE) is an intractable disorder characterized by slow spike-and-wave discharges in electroencephalograms (EEGs) and accompanied by severe cognitive dysfunction and neurodevelopmental or neurological deficits in humans. Administration of the cholesterol biosynthesis inhibitor AY-9944 (AY) during the postnatal developmental period induces AAE in animals; however, the neural mechanism of seizure development remains largely unknown. In this study, we characterized the cellular manifestations of AY-induced AAE in the mouse. Treatment of brain slices with AY increased membrane excitability of hippocampal CA1 neurons. AY treatment also increased input resistance of CA1 neurons during early postnatal days (PND) 5-10. However, these effects were not observed during late PND (14-21) or in adulthood (7-10 weeks). Notably, AY treatment elicited paroxysmal depolarizing shift (PDS)-like epileptiform discharges during the early postnatal period, but not during late PND or in adults. The PDS-like events were not compromised by application of glutamate or GABA receptor antagonists. However, the PDS-like events were abolished by blockage of voltage-gated Na(+) channels. Hippocampal neurons isolated from an in vivo AY model of AAE showed similar PDS-like epileptiform discharges. Further, AY-treated neurons from T-type Ca(2+) channel α1G knockout (Cav3.1(-/-)) mice, which do not exhibit typical absence seizures, showed similar PDS-like epileptiform discharges. These results demonstrate that PDS-like epileptiform discharges during the early postnatal period are dependent upon Na(+) channels and are involved in the generation of AY-induced AAE, which is distinct from typical absence epilepsy. Our findings may aid our understanding of the pathophysiological mechanisms of clinical AAE in individuals, such as those with Lennox-Gastaut syndrome. PMID:25890840

  7. The Effect of Ciprofloxacin Injection on Genetically Absence Prone (Wag/Rij) Rat's Electroencephalogram Characteristics

    PubMed Central

    Moghimi, Ali; Mollazadeh, Samaneh; Rassouli, Fatemeh Behnam; Shiee, Reza; Khalilzade, Mohammad Ali

    2013-01-01

    Introduction Ciprofloxacin which was used in this study is a Fluoroquinolone (FQ). This kind of drug may cause epileptic seizures probably because of the inhibition of GABA binding to its receptors. Wag/Rij rats (an animal model for generalized absence epilepsy), were used as experimental subjects. Methods For EEG study, electrodes were inserted into the cortex of animals according to paxinos coordinates. After and before ciprofloxacin injection, EEG was recorded and their SWDs were compared with each others. Results Findings showed a significant increase in the mean number of seizures during recording period. But the mean number of SWDs during seizures did not show any significant differences between groups. Discussion These results may be due to involvement of GABA antagonistic effects of FQs and/or Mg2+ linked blockade of NMDA receptors. More researches are going to determine physiopathology of SWDs and find new effective substance against this kind of epilepsy. PMID:25337325

  8. A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy.

    PubMed

    Audenaert, D; Claes, L; Ceulemans, B; Löfgren, A; Van Broeckhoven, C; De Jonghe, P

    2003-09-23

    Generalized epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous syndrome with childhood onset, characterized by febrile seizures (FS) and a variety of afebrile epileptic seizure types. The authors performed a mutational analysis of SCN1B on 74 unrelated probands with GEFS+, FS, or FS plus (FS+). In a family with FS+ and early-onset absence epilepsy, a mutation was identified that predicts a deletion of five amino acids in the extracellular immunoglobulin-like domain of SCN1B and potential loss of function. SCN1B mutations are associated with GEFS+ and may have a role in the elicitation of absence seizures. PMID:14504340

  9. Functional Study of NIPA2 Mutations Identified from the Patients with Childhood Absence Epilepsy

    PubMed Central

    Xie, Han; Zhang, Yuehua; Zhang, Pingping; Wang, Jingmin; Wu, Ye; Wu, Xiru; Netoff, Theoden; Jiang, Yuwu

    2014-01-01

    Recently many genetic mutations that are associated with epilepsy have been identified. The protein NIPA2 (non-imprinted in Prader-Willi/Angelman syndrome region protein 2) is a highly selective magnesium transporter encoded by the gene NIPA2 in which we have found three mutations (p.I178F, p.N244S and p.N334_E335insD) within a population of patients with childhood absence epilepsy (CAE). In this study, immunofluorescence labeling, inductively coupled plasma-optical emission spectroscopy (ICP-OES), MTT metabolic rate detection and computational modeling were utilized to elucidate how these mutations result in CAE. We found in cultured neurons that NIPA2 (wild-type) proteins were localized to the cell periphery, whereas mutant proteins were not effectively trafficked to the cell membrane. Furthermore, we found a decrease in intracellular magnesium concentration in the neurons transfected with mutant NIPA2, but no effect on the survival of neurons. To understand how low intracellular magnesium resulted in hyperexcitability, we built and analyzed a computational model to simulate the effects of mutations. The model suggested that lower intracellular magnesium concentration enhanced synaptic N-methyl-D-aspartate receptor (NMDAR) currents. This study primarily reveals that a selective magnesium transporter NIPA2 may play a role in the pathogenesis of CAE. PMID:25347071

  10. Isolated P/Q Calcium Channel Deletion in Layer VI Corticothalamic Neurons Generates Absence Epilepsy

    PubMed Central

    Bomben, Valerie C.; Aiba, Isamu; Qian, Jing; Mark, Melanie D.; Herlitze, Stefan

    2016-01-01

    Generalized spike-wave seizures involving abnormal synchronization of cortical and underlying thalamic circuitry represent a major category of childhood epilepsy. Inborn errors of Cacna1a, the P/Q-type voltage-gated calcium channel α subunit gene, expressed throughout the brain destabilize corticothalamic rhythmicity and produce this phenotype. To determine the minimal cellular lesion required for this network disturbance, we used neurotensin receptor 1 (Ntsr1) cre-driver mice to ablate floxed Cacna1a in layer VI pyramidal neurons, which supply the sole descending cortical synaptic input to thalamocortical relay cells and reticular interneurons and activate intrathalamic circuits. Targeted Cacna1a ablation in layer VI cells resulted in mice that display a robust spontaneous spike-wave absence seizure phenotype accompanied by behavioral arrest and inhibited by ethosuximide. To verify the selectivity of the molecular lesion, we determined that P/Q subunit proteins were reduced in corticothalamic relay neuron terminal zones, and confirmed that P/Q-mediated glutamate release was reduced at these synapses. Spike-triggered exocytosis was preserved by N-type calcium channel rescue, demonstrating that evoked release at layer VI terminals relies on both P/Q and N-type channels. Whereas intrinsic excitability of the P/Q channel depleted layer VI neurons was unaltered, T-type calcium currents in the postsynaptic thalamic relay and reticular cells were dramatically elevated, favoring rebound bursting and seizure generation. We find that an early P/Q-type release defect, limited to synapses of a single cell-type within the thalamocortical circuit, is sufficient to remodel synchronized firing behavior and produce a stable generalized epilepsy phenotype. SIGNIFICANCE STATEMENT This study dissects a critical component of the corticothalamic circuit in spike-wave epilepsy and identifies the developmental importance of P/Q-type calcium channel-mediated presynaptic glutamate release

  11. Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy.

    PubMed

    Cain, Stuart M; Tyson, John R; Jones, Karen L; Snutch, Terrance P

    2015-06-01

    Burst-firing in distinct subsets of thalamic relay (TR) neurons is thought to be a key requirement for the propagation of absence seizures. However, in the well-regarded Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model as yet there has been no link described between burst-firing in TR neurons and spike-and-wave discharges (SWDs). GAERS ventrobasal (VB) neurons are a specific subset of TR neurons that do not normally display burst-firing during absence seizures in the GAERS model, and here, we assessed the underlying relationship of VB burst-firing with Ih and T-type calcium currents between GAERS and non-epileptic control (NEC) animals. In response to 200-ms hyperpolarizing current injections, adult epileptic but not pre-epileptic GAERS VB neurons displayed suppressed burst-firing compared to NEC. In response to longer duration 1,000-ms hyperpolarizing current injections, both pre-epileptic and epileptic GAERS VB neurons required significantly more hyperpolarizing current injection to burst-fire than those of NEC animals. The current density of the Hyperpolarization and Cyclic Nucleotide-activated (HCN) current (Ih) was found to be increased in GAERS VB neurons, and the blockade of Ih relieved the suppressed burst-firing in both pre-epileptic P15-P20 and adult animals. In support, levels of HCN-1 and HCN-3 isoform channel proteins were increased in GAERS VB thalamic tissue. T-type calcium channel whole-cell currents were found to be decreased in P7-P9 GAERS VB neurons, and also noted was a decrease in CaV3.1 mRNA and protein levels in adults. Z944, a potent T-type calcium channel blocker with anti-epileptic properties, completely abolished hyperpolarization-induced VB burst-firing in both NEC and GAERS VB neurons. PMID:24953239

  12. Paroxysmal tonic upgaze of childhood with co-existent absence epilepsy.

    PubMed

    Luat, Aimée F; Asano, Eishi; Chugani, Harry T

    2007-09-01

    Paroxysmal tonic upgaze (PTU) is a childhood oculomotor syndrome of unclear etiology characterized by episodic tonic upward eye deviation with neck flexion. Neuroimaging findings are often normal and the electroencephalography during episodes is typically normal. We describe a 2-year-old boy who presented with macrocephaly, hypotonia, developmental delay and episodes of eye fluttering, head nodding and unresponsiveness. Video-EEG captured absence seizures and he was treated with valproate, which led to improvement of his seizures. However, two weeks after treatment, he developed paroxysmal episodes of "eyes up and chin down" movements lasting for hours at a time which were captured by home video. The episodes were relieved by sleep and exacerbated by fever, stress and even tactile stimulation. Increasing the dose of valproate resulted in increased frequency of the episodes. A repeat video-EEG disclosed the non-epileptic nature of these events. Discontinuation of valproate dramatically decreased the episodes. This case illustrates that paroxysmal tonic upgaze of childhood may co-exist with early onset absence epilepsy. Furthermore, valproate treatment may be associated with the development or unmasking of PTU suggesting that the pathophysiology of PTU may involve abnormal GABA neurotransmission. [Published with videosequences]. PMID:17884759

  13. Decreased viability and absence-like epilepsy in mice lacking or deficient in the GABAA receptor α1 subunit.

    PubMed

    Arain, Fazal M; Boyd, Kelli L; Gallagher, Martin J

    2012-08-01

    Autosomal dominant mutations S326fs328X and A322D in the GABA(A) receptor α1 subunit are associated with human absence epilepsy and juvenile myoclonic epilepsy, respectively. Because these mutations substantially reduce α1 subunit protein expression in vitro, it was hypothesized that they produce epilepsy by causing α1 subunit haploinsufficiency. However, in a mixed background strain of mice, α1 subunit deletion does not reduce viability or cause visually apparent seizures; the effects of α1 subunit deletion on electroencephalography (EEG) waveforms were not investigated. Here, we determined the effects of α1 subunit loss on viability, EEG spike-wave discharges and seizures in congenic C57BL/6J and DBA/2J mice. Deletion of α1 subunit caused strain- and sex-dependent reductions in viability. Heterozygous mice experienced EEG discharges and absence-like seizures within both background strains, and exhibited a sex-dependent effect on the discharges and viability in the C57BL/6J strain. These findings suggest that α1 subunit haploinsufficiency can produce epilepsy and may be a major mechanism by which the S326fs328X and A322D mutations cause these epilepsy syndromes. PMID:22812724

  14. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    PubMed Central

    Tavares, J.G.P.; Vasques, E.R.; Arida, R.M.; Cavalheiro, E.A.; Cabral, F.R.; Torres, L.B.; Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A.; Godoy, C.M.G.; Gomes da Silva, S.

    2015-01-01

    The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode. PMID:25590352

  15. Absence seizure

    MedlinePlus

    Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff RB, ... 6th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap ...

  16. Absence seizure

    MedlinePlus

    Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  17. Epilepsy

    MedlinePlus

    Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters ... may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, ...

  18. Diminished Presynaptic GABAB Receptor Function in the Neocortex of a Genetic Model of Absence Epilepsy

    PubMed Central

    Inaba, Yugi; D’Antuono, Margherita; Bertazzoni, Giuliano; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    Changes in GABAB receptor subunit expression have been recently reported in the neocortex of epileptic WAG/Rij rats that are genetically prone to experience absence seizures. These alterations may lead to hyperexcitability by down-regulating the function of presynaptic GABAB receptors in neocortical networks as suggested by a reduction in paired-pulse depression. Here, we tested further this hypothesis by analyzing the effects induced by the GABAB receptor agonist baclofen (0.1–10 μM) on the inhibitory events recorded in vitro from neocortical slices obtained from epileptic (>180 day-old) WAG/Rij and age-matched, non-epileptic control (NEC) rats. We found that higher doses of baclofen were required to depress pharmacologically isolated, stimulus-induced IPSPs generated by WAG/Rij neurons as compared to NEC. We also obtained similar evidence by comparing the effects of baclofen on the rate of occurrence of synchronous GABAergic events recorded by WAG/Rij and NEC neocortical slices treated with 4-aminopyridine + glutamatergic receptor antagonists. In conclusion, these data highlight a decreased function of presynaptic GABAB receptors in the WAG/Rij rat neocortex. We propose that this alteration may contribute to neocortical hyperexcitability and thus to absence seizures. PMID:19176980

  19. On-off intermittency of thalamo-cortical neuronal network oscillations in the electroencephalogram of rodents with genetic predisposition to absence epilepsy

    NASA Astrophysics Data System (ADS)

    Hramov, Alexander E.; Grubov, Vadim V.; Pavlov, Alexey N.; Sitnikova, Evgenija Yu.; Koronovskii, Alexey A.; Runnova, Anastasija E.; Shurugina, Sveltlana A.; Ivanov, Alexey V.

    2013-02-01

    Spike-wave discharges are electroencephalographic hallmarks of absence epilepsy. Spike-wave discharges are known to originate from thalamo-cortical neuronal network that normally produces sleep spindle oscillations. Although both sleep spindles and spike-wave discharges are considered as thalamo-cortical oscillations, functional relationship between them is still uncertain. The present study describes temporal dynamics of spike-wave discharges and sleep spindles as determined in long-time electroencephalograms (EEG) recorded in WAG/Rij rat model of absence epilepsy. We have proposed the wavelet-based method for the automatic detection of spike-wave discharges, sleep spindles (10-15Hz) and 5-9Hz oscillations in EEG. It was found that non-linear dynamics of spike-wave discharges and sleep spindles fits well to the law of 'on-off intermittency'. Intermittency in sleep spindles and spike-wave discharges implies that (1) temporal dynamics of these oscillations are deterministic in nature, and (2) it might be controlled by a system-level mechanism responsible for circadian modulation of neuronal network activity.

  20. Impairment of immunological functions in genetically epilepsy-prone rats.

    PubMed

    De Sarro, G; Liberto, M C; Berlinghieri, M C; Focà, A; Aragona, M; Cavaliere, R; Gulletta, E

    1996-06-01

    1. In genetically epilepsy-prone rats (GEPR-9s), which represent a natural genetic model of epilepsy, we observed that the number of peritoneal macrophages was significantly lower with respect to normal rats, and that some functional parameters (i.e. phagocytosis and intracellular killing) of these macrophages were impaired. 2. The count of lymphocyte populations showed a predominance of T-helper over T-cytotoxic/suppressor both in the spleen and lymph nodes. Moreover, an increased T-cell/B-cell ratio was observed in GEPR-9s. Flow cytometry revealed that GEPR-9s spleens possessed a large percentage of T-helper cells in comparison to normal rats. 3. By using concanavalin A-induced proliferation of GEPR-9s cultured lymphocytes, we have shown increased functional activation. 4. We suggest that the alterations in T-cell functions in GEPR-9s could be due to the involvement of the neuroendocrine system in the modulation of immunity, in the shift between Th1 and Th2, and in the activation of stress response. PMID:8853298

  1. Dysgraphia as a Mild Expression of Dystonia in Children with Absence Epilepsy

    PubMed Central

    Guerrini, Renzo; Melani, Federico; Brancati, Claudia; Ferrari, Anna Rita; Brovedani, Paola; Biggeri, Annibale; Grisotto, Laura; Pellacani, Simona

    2015-01-01

    Background Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia. Objectives Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer’s cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia. Methods We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.7) and average intelligence and compared them with 89 age-, gender- and class-matched healthy children (mean age 10.57) using tests for handwriting fluency and quality, based on which we divided patients and controls into four subgroups: AE/dysgraphia, AE without dysgraphia, controls with dysgraphia and healthy controls. We compared the blink reflex recovery cycle in children belonging to all four subgroups. Results We identified dysgraphia in 17/82 children with AE and in 7/89 controls (20.7 vs 7.8%; P = 0.016) with the former having a 3.4-times higher risk of dysgraphia regardless of age and gender (odd ratio: 3.49; 95% CI 1.2, 8.8%). The AE/dysgraphia subgroup performed worse than controls with dysgraphia in one test of handwriting fluency (P = 0.037) and in most trials testing handwriting quality (P< 0.02). In children with AE/dysgraphia the blink reflex showed no suppression at short interstimulus intervals, with a difference for each value emerging when comparing the study group with the three remaining subgroups (P<0.001). Conclusions In children with AE, dysgraphia is highly prevalent and has a homogeneous, distinctive pathophysiological substrate consistent with idiopathic dystonia. PMID:26132164

  2. Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy

    PubMed Central

    Masur, David; Shinnar, Shlomo; Cnaan, Avital; Shinnar, Ruth C.; Clark, Peggy; Wang, Jichuan; Weiss, Erica F.; Hirtz, Deborah G.

    2013-01-01

    Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine short-term differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine. Methods: Subjects with newly diagnosed CAE entering a double-blind, randomized controlled clinical trial had neuropsychological testing including assessments of general intellectual functioning, attention, memory, executive function, and achievement. Attention was reassessed at the week 16–20 visit. Results: At study entry, 36% of the cohort exhibited attention deficits despite otherwise intact neurocognitive functioning. Structural equation modeling of baseline neuropsychological data revealed a direct sequential effect among attention, memory, executive function, and academic achievement. At the week 16–20 visit, attention deficits persisted even if seizure freedom was attained. More subjects receiving valproic acid (49%) had attention deficits than subjects receiving ethosuximide (32%) or lamotrigine (24%) (p = 0.0006). Parental assessment did not reliably detect attention deficits before or after treatment (p < 0.0001). Conclusions: Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted. Classification of evidence: This study provides Class I evidence that valproic acid is associated with more significant attentional dysfunction than ethosuximide or lamotrigine in children with newly diagnosed CAE. PMID:24089388

  3. Quantification of Interictal Neuromagnetic Activity in Absence Epilepsy with Accumulated Source Imaging.

    PubMed

    Xiang, Jing; Tenney, Jeffrey R; Korman, Abraham M; Leiken, Kimberly; Rose, Douglas F; Harris, Elana; Yuan, Weihong; Horn, Paul S; Holland, Katherine; Loring, David W; Glauser, Tracy A

    2015-11-01

    Aberrant brain activity in childhood absence epilepsy (CAE) during seizures has been well recognized as synchronous 3 Hz spike-and-wave discharges on electroencephalography. However, brain activity from low- to very high-frequency ranges in subjects with CAE between seizures (interictal) has rarely been studied. Using a high-sampling rate magnetoencephalography (MEG) system, we studied ten subjects with clinically diagnosed but untreated CAE in comparison with age- and gender-matched controls. MEG data were recorded from all subjects during the resting state. MEG sources were assessed with accumulated source imaging, a new method optimized for localizing and quantifying spontaneous brain activity. MEG data were analyzed in nine frequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-55 Hz), high-gamma (65-90 Hz), ripple (90-200 Hz), high-frequency oscillation (HFO, 200-1,000 Hz), and very high-frequency oscillation (VHFO, 1,000-2,000 Hz). MEG source imaging revealed that subjects with CAE had higher odds of interictal brain activity in 200-1,000 and 1,000-2,000 Hz in the parieto-occipito-temporal junction and the medial frontal cortices as compared with controls. The strength of the interictal brain activity in these regions was significantly elevated in the frequency bands of 90-200, 200-1,000 and 1,000-2,000 Hz for subjects with CAE as compared with controls. The results indicate that CAE has significantly aberrant brain activity between seizures that can be noninvasively detected. The measurements of high-frequency neuromagnetic oscillations may open a new window for investigating the cerebral mechanisms of interictal abnormalities in CAE. PMID:25359158

  4. Epilepsy

    MedlinePlus

    Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions ...

  5. Altered Cortical GABAA Receptor Composition, Physiology, and Endocytosis in a Mouse Model of a Human Genetic Absence Epilepsy Syndrome*

    PubMed Central

    Zhou, Chengwen; Huang, Zhiling; Ding, Li; Deel, M. Elizabeth; Arain, Fazal M.; Murray, Clark R.; Patel, Ronak S.; Flanagan, Christopher D.; Gallagher, Martin J.

    2013-01-01

    Patients with generalized epilepsy exhibit cerebral cortical disinhibition. Likewise, mutations in the inhibitory ligand-gated ion channels, GABAA receptors (GABAARs), cause generalized epilepsy syndromes in humans. Recently, we demonstrated that heterozygous knock-out (Hetα1KO) of the human epilepsy gene, the GABAAR α1 subunit, produced absence epilepsy in mice. Here, we determined the effects of Hetα1KO on the expression and physiology of GABAARs in the mouse cortex. We found that Hetα1KO caused modest reductions in the total and surface expression of the β2 subunit but did not alter β1 or β3 subunit expression, results consistent with a small reduction of GABAARs. Cortices partially compensated for Hetα1KO by increasing the fraction of residual α1 subunit on the cell surface and by increasing total and surface expression of α3, but not α2, subunits. Co-immunoprecipitation experiments revealed that Hetα1KO increased the fraction of α1 subunits, and decreased the fraction of α3 subunits, that associated in hybrid α1α3βγ receptors. Patch clamp electrophysiology studies showed that Hetα1KO layer VI cortical neurons exhibited reduced inhibitory postsynaptic current peak amplitudes, prolonged current rise and decay times, and altered responses to benzodiazepine agonists. Finally, application of inhibitors of dynamin-mediated endocytosis revealed that Hetα1KO reduced base-line GABAAR endocytosis, an effect that probably contributes to the observed changes in GABAAR expression. These findings demonstrate that Hetα1KO exerts two principle disinhibitory effects on cortical GABAAR-mediated inhibitory neurotransmission: 1) a modest reduction of GABAAR number and 2) a partial compensation with GABAAR isoforms that possess physiological properties different from those of the otherwise predominant α1βγ GABAARs. PMID:23744069

  6. Absence epileptic activity changing effects of non-adenosine nucleoside inosine, guanosine and uridine in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Kovács, Z; Kékesi, K A; Dobolyi, Á; Lakatos, R; Juhász, G

    2015-08-01

    Adenosine (Ado) and non-adenosine (non-Ado) nucleosides such as inosine (Ino), guanosine (Guo) and uridine (Urd) may have regionally different roles in the regulation of physiological and pathophysiological processes in the central nervous system (CNS) such as epilepsy. It was demonstrated previously that Ino and Guo decreased quinolinic acid (QA)-induced seizures and Urd reduced penicillin-, bicuculline- and pentylenetetrazole (PTZ)-induced seizures. It has also been demonstrated that Ino and Urd may exert their effects through GABAergic system by altering the function of GABA(A) type of gamma-aminobutyric acid receptors (GABAA receptors) whereas Guo decreases glutamate-induced excitability through glutamatergic system, which systems (GABAergic and glutamatergic) are involved in pathomechanisms of absence epilepsy. Thus, we hypothesized that Ino and Guo, similarly to the previously described effect of Urd, might also decrease absence epileptic activity. We investigated in the present study whether intraperitoneal (i.p.) application of Ino (500 and 1000mg/kg), Guo (20 and 50mg/kg), Urd (500 and 1000mg/kg), GABA(A) receptor agonist muscimol (1 and 3mg/kg), GABA(A) receptor antagonist bicuculline (2 and 4mg/kg), non-selective Ado receptor antagonist theophylline (5 and 10mg/kg) and non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate (MK-801, 0.0625 and 0.1250mg/kg) alone and in combination have modulatory effects on absence epileptic activity in Wistar Albino Glaxo Rijswijk (WAG/Rij) rats. We found that Guo decreased the number of spike-wave discharges (SWDs) whereas Ino increased it dose-dependently. We strengthened that Urd can decrease absence epileptic activity. Our results suggest that Guo, Urd and their analogs could be potentially effective drugs for treatment of human absence epilepsy. PMID:26037802

  7. Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy.

    PubMed

    Nabbout, R; Kozlovski, A; Gennaro, E; Bahi-Buisson, N; Zara, F; Chiron, C; Bianchi, A; Brice, A; Leguern, E; Dulac, O

    2003-10-01

    Myoclonic astatic epilepsy (MAE) is a genetically determined condition of childhood onset characterized by multiple generalized types of seizures including myoclonic astatic seizures, generalized spike waves and cognitive deterioration. This condition has been reported in a few patients in generalized epilepsy with febrile seizures plus (GEFS+) families and MAE has been considered, like severe myoclonic epilepsy of infancy (SMEI), to be a severe phenotype within the GEFS+ spectrum. Four genes have been identified in GEFS+ families, but only three (SCN1A, SCNlB, GABRG2) were found in MAE patients within GEFS+ families. We analysed these three genes in a series of 22 sporadic patients with MAE and found no causal mutations. These findings suggest that MAE, unlike SMEI, is not genetically related to GEFS+. Although MAE and SMEI share the same types of seizures, only SMEI patients are sensitive to fever. This is probably its main link to GEFS+. A different family of genes is likely to account for MAE. PMID:14642997

  8. Reticular nucleus-specific changes in alpha3 subunit protein at GABA synapses in genetically epilepsy-prone rats.

    PubMed

    Liu, Xiao-Bo; Coble, Jeffrey; van Luijtelaar, Gilles; Jones, Edward G

    2007-07-24

    Differential composition of GABA(A) receptor (GABA(A)R) subunits underlies the variability of fast inhibitory synaptic transmission; alteration of specific GABA(A)R subunits in localized brain regions may contribute to abnormal brain states such as absence epilepsy. We combined immunocytochemistry and high-resolution ImmunoGold electron microscopy to study cellular and subcellular localization of GABA(A)R alpha1, alpha3, and beta2/beta3 subunits in ventral posterior nucleus (VP) and reticular nucleus (RTN) of control rats and WAG/Rij rats, a genetic model of absence epilepsy. In control rats, alpha1 subunits were prominent at inhibitory synapses in VP and much less prominent in RTN; in contrast, the alpha3 subunit was highly evident at inhibitory synapses in RTN. beta2/beta3 subunits were evenly distributed at inhibitory synapses in both VP and RTN. ImmunoGold particles representing all subunits were concentrated at postsynaptic densities with no extrasynaptic localization. Calculated mean number of particles for alpha1 subunit per postsynaptic density in nonepileptic VP was 6.1 +/- 3.7, for alpha3 subunit in RTN it was 6.6 +/- 3.4, and for beta2/beta3 subunits in VP and RTN the mean numbers were 3.7 +/- 1.3 and 3.5 +/- 1.2, respectively. In WAG/Rij rats, there was a specific loss of alpha3 subunit immunoreactivity at inhibitory synapses in RTN, without reduction in alpha3 subunit mRNA or significant change in immunostaining for other markers of RTN cell identity such as GABA or parvalbumin. alpha3 immunostaining in cortex was unchanged. Subtle, localized changes in GABA(A)R expression acting at highly specific points in the interconnected thalamocortical network lie at the heart of idiopathic generalized epilepsy. PMID:17630284

  9. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats

    PubMed Central

    D’Amore, V.; Santolini, I.; van Rijn, C.M.; Biagioni, F.; Molinaro, G.; Prete, A.; Conn, P.J.; Lindsley, C.W.; Zhou, Y.; Vinson, P.N.; Rodriguez, A.L.; Jones, C.K.; Stauffer, S.R.; Nicoletti, F.; van Luijtelaar, G.; Ngomba, R.T.

    2013-01-01

    Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. PMID:22705340

  10. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats.

    PubMed

    D'Amore, V; Santolini, I; van Rijn, C M; Biagioni, F; Molinaro, G; Prete, A; Conn, P J; Lindsley, C W; Zhou, Y; Vinson, P N; Rodriguez, A L; Jones, C K; Stauffer, S R; Nicoletti, F; van Luijtelaar, G; Ngomba, R T

    2013-03-01

    Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. PMID:22705340

  11. Optimized methods for epilepsy therapy development using an etiologically realistic model of focal epilepsy in the rat

    PubMed Central

    Eastman, Clifford L.; Fender, Jason S.; Temkin, Nancy R.; D’Ambrosio, Raimondo

    2015-01-01

    Conventionally developed antiseizure drugs fail to control epileptic seizures in about 30% of patients, and no treatment prevents epilepsy. New etiologically realistic, syndrome-specific epilepsy models are expected to identify better treatments by capturing currently unknown ictogenic and epileptogenic mechanisms that operate in the corresponding patient populations. Additionally, the use of electrocorticography permits better monitoring of epileptogenesis and the full spectrum of acquired seizures, including focal nonconvulsive seizures that are typically difficult to treat in humans. Thus, the combined use of etiologically realistic models and electrocorticography may improve our understanding of the genesis and progression of epilepsy, and facilitate discovery and translation of novel treatments. However, this approach is labor intensive and must be optimized. To this end, we used an etiologically realistic rat model of posttraumatic epilepsy, in which the initiating fluid percussion injury closely replicates contusive closed-head injury in humans, and has been adapted to maximize epileptogenesis and focal non-convulsive seizures. We obtained week-long 5-electrode electrocorticography 1 month post-injury, and used a Monte-Carlo-based non-parametric bootstrap strategy to test the impact of electrode montage design, duration-based seizure definitions, group size and duration of recordings on the assessment of posttraumatic epilepsy, and on statistical power to detect antiseizure and antiepileptogenic treatment effects. We found that use of seizure definition based on clinical criteria rather than event duration, and of recording montages closely sampling the activity of epileptic foci, maximize the power to detect treatment effects. Detection of treatment effects was marginally improved by prolonged recording, and 24 h recording epochs were sufficient to provide 80% power to detect clinically interesting seizure control or prevention of seizures with small groups

  12. Optimized methods for epilepsy therapy development using an etiologically realistic model of focal epilepsy in the rat.

    PubMed

    Eastman, Clifford L; Fender, Jason S; Temkin, Nancy R; D'Ambrosio, Raimondo

    2015-02-01

    Conventionally developed antiseizure drugs fail to control epileptic seizures in about 30% of patients, and no treatment prevents epilepsy. New etiologically realistic, syndrome-specific epilepsy models are expected to identify better treatments by capturing currently unknown ictogenic and epileptogenic mechanisms that operate in the corresponding patient populations. Additionally, the use of electrocorticography permits better monitoring of epileptogenesis and the full spectrum of acquired seizures, including focal nonconvulsive seizures that are typically difficult to treat in humans. Thus, the combined use of etiologically realistic models and electrocorticography may improve our understanding of the genesis and progression of epilepsy, and facilitate discovery and translation of novel treatments. However, this approach is labor intensive and must be optimized. To this end, we used an etiologically realistic rat model of posttraumatic epilepsy, in which the initiating fluid percussion injury closely replicates contusive closed-head injury in humans, and has been adapted to maximize epileptogenesis and focal non-convulsive seizures. We obtained week-long 5-electrode electrocorticography 1 month post-injury, and used a Monte-Carlo-based non-parametric bootstrap strategy to test the impact of electrode montage design, duration-based seizure definitions, group size and duration of recordings on the assessment of posttraumatic epilepsy, and on statistical power to detect antiseizure and antiepileptogenic treatment effects. We found that use of seizure definition based on clinical criteria rather than event duration, and of recording montages closely sampling the activity of epileptic foci, maximize the power to detect treatment effects. Detection of treatment effects was marginally improved by prolonged recording, and 24h recording epochs were sufficient to provide 80% power to detect clinically interesting seizure control or prevention of seizures with small groups

  13. Epilepsy.

    PubMed

    Krishnamurthy, Kaarkuzhali B

    2016-02-01

    This issue provides a clinical overview of epilepsy, focusing on diagnosis, prevention, treatment, and further considerations. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID:26829918

  14. Cannabis agonist injection effect on the coupling architecture in cortex of WAG/Rij rats during absence seizures

    NASA Astrophysics Data System (ADS)

    Sysoeva, Marina V.; Kuznetsova, Galina D.; van Rijn, Clementina M.; Sysoev, Ilya V.

    2016-04-01

    WAG/Rij rats are well known genetic model of absence epilepsy, which is traditionally considered as a nonconvulsive generalised epilepsy of unknown aetiology. In current study the effect of (R)-(+)-WIN 55,212-2 (cannabis agonist) injection on the coupling between different parts of cortex was studied on 27 male 8 month old rats using local field potentials. Recently developed non-linear adapted Granger causality approach was used as a primary method. It was shown that first 2 hours after the injection the coupling between most channel pairs rises in comparison with the spontaneous activity, whilst long after the injection (2-6 hours) it drops down. The coupling increase corresponds to the mentioned before treatment effect, when the number and the longitude of seizures significantly decreases. However the subsequent decrease of the coupling in the cortex is accompanied by the dramatic increase of the longitude and the number of seizures. This assumes the hypothesis that a relatively higher coupling in the cortical network can prevent the seizure propagation and generalisation.

  15. Spike-Wave Discharges in Adult Sprague-Dawley Rats and Their Implications for Animal Models of Temporal Lobe Epilepsy

    PubMed Central

    Pearce, Patrice S.; Friedman, Daniel; LaFrancois, John J.; Iyengar, Sloka S.; Fenton, André A.; MacLusky, Neil J.; Scharfman, Helen E

    2014-01-01

    Spike-wave discharges (SWDs) are thalamocortical oscillations that are often considered to be the EEG correlate of absence seizures. GAERS and Wag/Rij rat strains exhibit SWDs and are considered to be genetic animal models of absence epilepsy. However, it has been reported that other rat strains have SWDs, suggesting that SWDs may vary in their prevalence but all rats have a predisposition for them. This is important because many of these rat strains are used to study temporal lobe epilepsy (TLE), where it is assumed that there is no seizure-like activity in controls. In the course of other studies about the Sprague-Dawley rat, a common rat strain for animal models of TLE, we found that approximately 19% of 2–3 month old naïve female Sprague-Dawley rats exhibited SWDs spontaneously during periods of behavioral arrest and they continued for months. Males exhibited SWDs only after 3 months of age, consistent with previous reports [1]. Housing in atypical lighting during early life appeared to facilitate the incidence SWDs. SWDs were often accompanied by behaviors similar to stage 1–2 limbic seizures. Therefore, additional analyses were made to address the similarity. We observed that the frequency of SWDs was similar to theta rhythm during exploration for a given animal, typically 7–8 Hz. Therefore, activity in the frequency of theta rhythm that occurs during frozen behavior may not reflect seizures necessarily. Hippocampal recordings exhibited high frequency oscillations (>250 Hz) during SWDs, suggesting neuronal activity in hippocampus occurs during SWDs, i.e., it is not a passive structure. The data also suggest that high frequency oscillations, if rhythmic, may reflect SWDs. We also confirmed that SWDs were present in a common animal model of TLE, the pilocarpine model, using female Sprague-Dawley rats. Therefore, damage and associated changes to thalamic, hippocampal and cortical neurons in does not prevent SWDs, at least in this animal model. The results

  16. Dynamics of epileptic activity in a peculiar case of childhood absence epilepsy and correlation with thalamic levels of GABA

    PubMed Central

    Leal, Alberto; Vieira, José P.; Lopes, Ricardo; Nunes, Rita G.; Gonçalves, Sónia I.; Lopes da Silva, Fernando; Figueiredo, Patrícia

    2016-01-01

    Objectives Childhood absence epilepsy (CAE) is a syndrome with well-defined electroclinical features but unknown pathological basis. An increased thalamic tonic GABA inhibition has recently been discovered on animal models (Cope et al., 2009), but its relevance for human CAE is unproven. Methods We studied an 11-year-old boy, presenting the typical clinical features of CAE, but spike–wave discharges (SWD) restricted to one hemisphere. Results High-resolution EEG failed to demonstrate independent contralateral hemisphere epileptic activity. Consistently, simultaneous EEG–fMRI revealed the typical thalamic BOLD activation, associated with caudate and default mode network deactivation, but restricted to the hemisphere with SWD. Cortical BOLD activations were localized on the ipsilateral pars transverse. Magnetic resonance spectroscopy, using MEGA-PRESS, showed that the GABA/creatine ratio was 2.6 times higher in the hemisphere with SWD than in the unaffected one, reflecting a higher GABA concentration. Similar comparisons for the patient's occipital cortex and thalamus of a healthy volunteer yielded asymmetries below 25%. Significance In a clinical case of CAE with EEG and fMRI-BOLD manifestations restricted to one hemisphere, we found an associated increase in thalamic GABA concentration consistent with a role for this abnormality in human CAE. PMID:27144122

  17. Novel combinations of phenotypic biomarkers predict development of epilepsy in the lithium-pilocarpine model of temporal lobe epilepsy in rats.

    PubMed

    Bröer, Sonja; Löscher, Wolfgang

    2015-12-01

    The discovery and validation of biomarkers in neurological and neurodegenerative diseases is an important challenge for early diagnosis of disease and for the development of therapeutics. Epilepsy is often a consequence of brain insults such as traumatic brain injury or stroke, but as yet no biomarker exists to predict the development of epilepsy in patients at risk. Given the complexity of epilepsy, it is unlikely that a single biomarker is sufficient for this purpose, but a combinatorial approach may be needed to overcome the challenge of individual variability and disease heterogeneity. The goal of the present prospective study in the lithium-pilocarpine model of epilepsy in rats was to determine the discriminative utility of combinations of phenotypic biomarkers by examining their ability to predict epilepsy. For this purpose, we used a recent model refinement that allows comparing rats that will or will not develop spontaneous recurrent seizures (SRS) after pilocarpine-induced status epilepticus (SE). Potential biomarkers included in our study were seizure threshold and seizure severity in response to timed i.v. infusion of pentylenetetrazole (PTZ) and behavioral alterations determined by a battery of tests during the three weeks following SE. Three months after SE, video/EEG monitoring was used to determine which rats had developed SRS. To determine whether a biomarker or combination of biomarkers performed better than chance at predicting epilepsy after SE, derived data underwent receiver operating characteristic (ROC) curve analyses. When comparing rats with and without SRS and sham controls, the best intergroup discrimination was obtained by combining all measurements, resulting in a ROC area under curve (AUC) of 0.9592 (P<0.01), indicating an almost perfect discrimination or accuracy to predict development of SRS. These data indicate that a combinatorial biomarker approach may overcome the challenge of individual variability in the prediction of epilepsy

  18. Spontaneous motor seizures of rats with kainate-induced epilepsy: effect of time of day and activity state.

    PubMed

    Hellier, J L; Dudek, F E

    1999-05-01

    Kainate treatment in rats can result in a chronic behavioral state that is similar to human temporal lobe epilepsy. We tested the hypothesis that, like some humans with epilepsy, rat with kainate-induced epilepsy have more spontaneous motor seizures during inactivity (i.e. little to no volitional movement, including apparent sleep) than during activity (i.e. apparent volitional movement, as in walking, grooming, eating, etc.). Rats were given intraperitoneal (i.p.) injections of kainate (5 mg/kg) every hour so that class III/IV/V seizures were elicited for > or = 3 h. Seizure behavior was video-monitored (24 h for 5-6 days, n = 32 rats at 3 months and n = 23 rats at 4 months after treatment) to examine the occurrence of seizures as a function of light versus dark (12-12-h light-dark cycle) and inactivity versus activity. Significantly more spontaneous motor seizures occurred during inactive versus active states (82% vs. 18%, P = 0.0001). Although more seizures occurred during the light period than the dark, the difference was not significant (62% vs. 38%, P > 0. 1). These data suggest that the frequency of spontaneous motor seizures in the rat with kainate-induced epilepsy depends primarily on activity state rather than time of day (i.e. time during the light-dark cycle). The effect of inactivity on the occurrence of seizures in the rat with kainate-induced epilepsy appears similar to some forms of human epilepsy. PMID:10232794

  19. An EEG-fMRI Study on the Termination of Generalized Spike-And-Wave Discharges in Absence Epilepsy

    PubMed Central

    Benuzzi, Francesca; Ballotta, Daniela; Mirandola, Laura; Ruggieri, Andrea; Vaudano, Anna Elisabetta; Zucchelli, Micaela; Ferrari, Elisabetta; Nichelli, Paolo Frigio; Meletti, Stefano

    2015-01-01

    Introduction Different studies have investigated by means of EEG-fMRI coregistration the brain networks related to generalized spike-and-wave discharges (GSWD) in patients with idiopathic generalized epilepsy (IGE). These studies revealed a widespread GSWD-related neural network that involves the thalamus and regions of the default mode network. In this study we investigated which brain regions are critically involved in the termination of absence seizures (AS) in a group of IGE patients. Methods Eighteen patients (6 male; mean age 25 years) with AS were included in the EEG-fMRI study. Functional data were acquired at 3T with continuous simultaneous video-EEG recording. Event-related analysis was performed with SPM8 software, using the following regressors: (1) GSWD onset and duration; (2) GSWD offset. Data were analyzed at single-subject and at group level with a second level random effect analysis. Results A mean of 17 events for patient was recorded (mean duration of 4.2 sec). Group-level analysis related to GSWD onset respect to rest confirmed previous findings revealing thalamic activation and a precuneus/posterior cingulate deactivation. At GSWD termination we observed a decrease in BOLD signal over the bilateral dorsolateral frontal cortex respect to the baseline (and respect to GSWD onset). The contrast GSWD offset versus onset showed a BOLD signal increase over the precuneus-posterior cingulate region bilaterally. Parametric correlations between electro-clinical variables and BOLD signal at GSWD offset did not reveal significant effects. Conclusion The role of the decreased neural activity of lateral prefrontal cortex at GSWD termination deserve future investigations to ascertain if it has a role in promoting the discharge offset, as well as in the determination of the cognitive deficits often present in patients with AS. The increased BOLD signal at precuneal/posterior cingulate cortex might reflect the recovery of neural activity in regions that are

  20. Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy.

    PubMed Central

    D’Amour, James; Magagna-Poveda, Alejandra; Moretto, Jillian; Friedman, Daniel; LaFrancois, John J.; Pearce, Patrice; Fenton, Andre A.; MacLusky, Neil J.; Scharfman, Helen E.

    2015-01-01

    In catamenial epilepsy, seizures exhibit a cyclic pattern that parallels the menstrual cycle. Many studies suggest that catamenial seizures are caused by fluctuations in gonadal hormones during the menstrual cycle, but this has been difficult to study in rodent models of epilepsy because the ovarian cycle in rodents, called the estrous cycle, is disrupted by severe seizures. Thus, when epilepsy is severe, estrous cycles become irregular or stop. Therefore, we modified kainic acid (KA)- and pilocarpine-induced status epilepticus (SE) models of epilepsy so that seizures were rare for the first months after SE, and conducted video-EEG during this time. The results showed that interictal spikes (IIS) occurred intermittently. All rats with regular 4-day estrous cycles had IIS that waxed and waned with the estrous cycle. The association between the estrous cycle and IIS was strong: if the estrous cycles became irregular transiently, IIS frequency also became irregular, and when the estrous cycle resumed its 4-day pattern, IIS frequency did also. Furthermore, when rats were ovariectomized, or males were recorded, IIS frequency did not show a 4-day pattern. Systemic administration of an estrogen receptor antagonist stopped the estrous cycle transiently, accompanied by transient irregularity of the IIS pattern. Eventually all animals developed severe, frequent seizures and at that time both the estrous cycle and the IIS became irregular. We conclude that the estrous cycle entrains IIS in the modified KA and pilocarpine SE models of epilepsy. The data suggest that the ovarian cycle influences more aspects of epilepsy than seizure susceptibility. PMID:25864929

  1. Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy.

    PubMed

    D'Amour, James; Magagna-Poveda, Alejandra; Moretto, Jillian; Friedman, Daniel; LaFrancois, John J; Pearce, Patrice; Fenton, Andre A; MacLusky, Neil J; Scharfman, Helen E

    2015-07-01

    In catamenial epilepsy, seizures exhibit a cyclic pattern that parallels the menstrual cycle. Many studies suggest that catamenial seizures are caused by fluctuations in gonadal hormones during the menstrual cycle, but this has been difficult to study in rodent models of epilepsy because the ovarian cycle in rodents, called the estrous cycle, is disrupted by severe seizures. Thus, when epilepsy is severe, estrous cycles become irregular or stop. Therefore, we modified kainic acid (KA)- and pilocarpine-induced status epilepticus (SE) models of epilepsy so that seizures were rare for the first months after SE, and conducted video-EEG during this time. The results showed that interictal spikes (IIS) occurred intermittently. All rats with regular 4-day estrous cycles had IIS that waxed and waned with the estrous cycle. The association between the estrous cycle and IIS was strong: if the estrous cycles became irregular transiently, IIS frequency also became irregular, and when the estrous cycle resumed its 4-day pattern, IIS frequency did also. Furthermore, when rats were ovariectomized, or males were recorded, IIS frequency did not show a 4-day pattern. Systemic administration of an estrogen receptor antagonist stopped the estrous cycle transiently, accompanied by transient irregularity of the IIS pattern. Eventually all animals developed severe, frequent seizures and at that time both the estrous cycle and the IIS became irregular. We conclude that the estrous cycle entrains IIS in the modified KA and pilocarpine SE models of epilepsy. The data suggest that the ovarian cycle influences more aspects of epilepsy than seizure susceptibility. PMID:25864929

  2. Cognitive deficits and brain myo-Inositol are early biomarkers of epileptogenesis in a rat model of epilepsy.

    PubMed

    Pascente, Rosaria; Frigerio, Federica; Rizzi, Massimo; Porcu, Luca; Boido, Marina; Davids, Joe; Zaben, Malik; Tolomeo, Daniele; Filibian, Marta; Gray, William P; Vezzani, Annamaria; Ravizza, Teresa

    2016-09-01

    One major unmet clinical need in epilepsy is the identification of therapies to prevent or arrest epilepsy development in patients exposed to a potential epileptogenic insult. The development of such treatments has been hampered by the lack of non-invasive biomarkers that could be used to identify the patients at-risk, thereby allowing to design affordable clinical studies. Our goal was to test the predictive value of cognitive deficits and brain astrocyte activation for the development of epilepsy following a potential epileptogenic injury. We used a model of epilepsy induced by pilocarpine-evoked status epilepticus (SE) in 21-day old rats where 60-70% of animals develop spontaneous seizures after around 70days, although SE is similar in all rats. Learning was evaluated in the Morris water-maze at days 15 and 65 post-SE, each time followed by proton magnetic resonance spectroscopy for measuring hippocampal myo-Inositol levels, a marker of astrocyte activation. Rats were video-EEG monitored for two weeks at seven months post-SE to detect spontaneous seizures, then brain histology was done. Behavioral and imaging data were retrospectively analysed in epileptic rats and compared with non-epileptic and control animals. Rats displayed spatial learning deficits within three weeks from SE. However, only epilepsy-prone rats showed accelerated forgetting and reduced learning rate compared to both rats not developing epilepsy and controls. These deficits were associated with reduced hippocampal neurogenesis. myo-Inositol levels increased transiently in the hippocampus of SE-rats not developing epilepsy while this increase persisted until spontaneous seizures onset in epilepsy-prone rats, being associated with a local increase in S100β-positive astrocytes. Neuronal cell loss was similar in all SE-rats. Our data show that behavioral deficits, together with a non-invasive marker of astrocyte activation, predict which rats develop epilepsy after an acute injury. These measures

  3. GABAB receptors as a common target for hypothermia and spike and wave seizures: intersecting mechanisms of thermoregulation and absence epilepsy.

    PubMed

    Ostojić, Z S; Ilić, T V; Vesković, S M; Andjus, P R

    2013-05-15

    In the current study the link among the γ-hydroxybutyrate (GHB)/pentylenetetrazole (PTZ)-induced absence-like seizures and concomitant decreases in the core temperature, as well as electroencephalographic (EEG) activity during rewarming from deep hypothermia produced by a drug-free protocol were investigated. During the rewarming period after deep cooling, most Wistar rats suffered from bilaterally synchronous spike and waves with no or mild behavioral correlates. Spike and wave seizures were temperature-dependent and were initially registered when body temperature (Tb) reached 25-27°C, but mostly during the mild hypothermia of 0.3-1.3°C (Tb of 36.3-37.3°C). In chemical absence models, spike and wave discharges were also closely accompanied by mild systemic hypothermia, as both PTZ- and GHB-induced temperature decreases ranged from about 1-1.4°C respectively, together with EEG markers of absence activity. Thus, throughout the different experimental designs, the occurrence of spike and wave discharges was always related to a mild (0.3-1.4°C) decrease of Tb. Benzodiazepine diazepam as the GABAA-positive allosteric modulator and CGP 62349 as the selective antagonist of GABAB receptors were used to determine if their well-known anticonvulsant properties also affect hypothermia elicited by these drugs. Finally, during the course of spontaneous rewarming from deep hypothermia, another selective GABAB-blocking agent, CGP 35348, was used to elucidate if GABAB inhibitory system could be critically implicated in the generation of hypothermia-dependent spike and waves. Diazepam prevented both the PTZ-induced hypothermia and electrographic absence seizures, but these two beneficial effects did not occur in the GHB model. Even though diazepam delayed GHB-induced maximal temperature decrease, the GHB effects remained highly significant. The GABAB antagonist CGP 62349 completely prevented hypothermia as well as absence seizures in both chemical models. Likewise, spike and

  4. Down-regulation of adenylate kinase 5 in temporal lobe epilepsy patients and rat model.

    PubMed

    Lai, Yujie; Hu, Xiaotong; Chen, Guojun; Wang, Xuefeng; Zhu, Binglin

    2016-07-15

    Adenylate kinase 5 (AK5) is one member of the AK family and plays a critical role in maintaining cellular homeostasis. Different from the other AKs, AK5 is almost exclusively expressed in the brain. However, its exact biological functions remain unclear. The aim of the present study is to explore the expression pattern of AK5 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic rat model. Using Western blot, immunofluorescence and immunoprecipitation analysis, we found that AK5 protein was mainly expressed in neurons, demonstrated by colocalization with the dendritic marker, MAP2, which were similar to the corresponding controls. However, the expression of AK5 decreased remarkably in epileptic patients and experimental rats. Furthermore, immunoprecipitation analysis showed that the interaction of AK5 with copine VI (CPNE6, a brain specific protein) increased in epileptic patients and rat models. Our results are the first to indicate that the expression of AK5 in epileptic brain tissue may play important roles in epilepsy, especially refractory epilepsy. PMID:27288770

  5. Absence of pharmacokinetic interaction between ofloxacin and fenbufen in rats.

    PubMed

    Katagiri, Y; Naora, K; Ichikawa, N; Hayashibara, M; Iwamoto, K

    1989-10-01

    The possible pharmacokinetic interaction between a new quinolone and fenbufen was investigated by comparing the plasma concentration-time profiles and serum protein binding of ofloxacin, fenbufen and its active metabolite, felbinac, in rats. The rats were administered intravenous doses of ofloxacin (5 mg kg-1), fenbufen (10 mg kg-1) alone or concomitantly. The plasma elimination half-lives were about 55 min in both groups. A slight elevation of plasma concentration of ofloxacin and a small decrease of its total body clearance were observed after its coadministration with fenbufen. The extent of ofloxacin binding to rat serum tended to be slightly reduced by fenbufen which coexisted at relatively high concentrations. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected by the coadministration with ofloxacin. These results suggest that any substantive pharmacokinetic interaction may be unlikely after the concomitant administration of ofloxacin and fenbufen. PMID:2575153

  6. Absence of initiating activity by quercetin in the rat liver.

    PubMed

    Kato, K; Mori, H; Tanaka, T; Fujii, M; Kawai, T; Nishikawa, A; Takahashi, M; Hirono, I

    1985-08-01

    Initiating activity of quercetin was tested in rats which were treated with partial hepatectomy and given a liver cancer promoter, phenobarbital. A few intestinal neoplasms were seen but without significant difference in incidence from those in the quercetin-untreated group. Moreover, neither neoplastic nor preneoplastic liver changes were detected in quercetin-treated groups. With hepatocyte primary culture/DNA repair test, quercetin did not produce genotoxicity. The results show that quercetin has no initiating or genotoxic activities in the rat liver. PMID:4029060

  7. Epilepsy and hippocampal neurodegeneration induced by glutamate decarboxylase inhibitors in awake rats.

    PubMed

    Salazar, Patricia; Tapia, Ricardo

    2015-10-01

    Glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis, requires pyridoxal phosphate (PLP) as a cofactor. Thiosemicarbazide (TSC) and γ-glutamyl-hydrazone (PLPGH) inhibit the free PLP-dependent isoform (GAD65) activity after systemic administration, leading to epilepsy in mice and in young, but not in adult rats. However, the competitive GAD inhibitor 3-mercaptopropionic acid (MPA) induces convulsions in both immature and adult rats. In the present study we tested comparatively the epileptogenic and neurotoxic effects of PLPGH, TSC and MPA, administered by microdialysis in the hippocampus of adult awake rats. Cortical EEG and motor behavior were analyzed during the next 2h, and aspartate, glutamate and GABA were measured by HPLC in the microdialysis-collected fractions. Twenty-four hours after drug administration rats were fixed for histological analysis of the hippocampus. PLPGH or TSC did not affect the motor behavior, EEG or cellular morphology, although the extracellular concentration of GABA was decreased. In contrast, MPA produced intense wet-dog shakes, EEG epileptiform discharges, a >75% reduction of extracellular GABA levels and remarkable neurodegeneration of the CA1 region, with >80% neuronal loss. The systemic administration of the NMDA glutamate receptor antagonist MK-801 30 min before MPA did not prevent the MPA-induced epilepsy but significantly protected against its neurotoxic effect, reducing neuronal loss to <30%. We conclude that in adult awake rats, drugs acting on PLP availability have only a weak effect on GABA neurotransmission, whereas direct GAD inhibition produced by MPA induces hyperexcitation leading to epilepsy and hippocampal neurodegeneration. Because this degeneration was prevented by the blockade of NMDA receptors, we conclude that it is due to glutamate-mediated excitotoxicity consequent to disinhibition of the hippocampal excitatory circuits. PMID:26354164

  8. Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.

    PubMed

    Lakatos, Renáta Krisztina; Dobolyi, Árpád; Todorov, Mihail Ivilinov; Kékesi, Katalin A; Juhász, Gábor; Aleksza, Magdolna; Kovács, Zsolt

    2016-06-01

    The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system. PMID:27154620

  9. Leukocyte Infiltration Triggers Seizure Recurrence in a Rat Model of Temporal Lobe Epilepsy.

    PubMed

    Liu, Zanhua; Wang, Suping; Liu, Jinjie; Wang, Feng; Liu, Yi; Zhao, Yongbo

    2016-06-01

    Epilepsy, which affects about 1 % of the population worldwide, leads to poor prognosis and increased morbidity. However, effective drugs providing satisfactory control on seizure relapse were rare, which encouraged more etiological studies. Whether inflammation is one of key events underlying seizure is in debate. In order to explore the role of inflammatory in the pathogenesis and development of epilepsy, we conducted intra-caudal vein injection of leukocytes to aggravated brain inflammatory process in kainic acid-induced seizure model in this study. The results showed that intravenous administration of activated leukocytes increased the frequency and reduced the latent phase of seizure recurrences in rat models of epileptic seizure, during which leukocyte inflammation, brain-blood barrier damage, and neuron injury were also significantly aggravated, indicating that leukocyte infiltration might facilitate seizure recurrence through aggravating brain inflammation, brain-blood barrier damage, and neuron injury. PMID:27040283

  10. Cortical alterations in a model for absence epilepsy and febrile seizures: in vivo findings in mice carrying a human GABA(A)R gamma2 subunit mutation.

    PubMed

    Witsch, Jens; Golkowski, Daniel; Hahn, Thomas T G; Petrou, Steven; Spors, Hartwig

    2015-05-01

    Childhood absence epilepsy (CAE) is one of the most common forms of epilepsy among children. The study of a large Australian family demonstrated that a point mutation in the gene encoding the gamma2 subunit of the GABA(A) receptor (G2R43Q) leads to an autosomal dominantly inherited form of CAE and febrile seizures (FS). In a transgenic mouse model carrying the gamma2 (R43Q) mutation heterozygous animals recapitulate the human phenotype. In-vitro experiments indicated that this point mutation impairs cortical inhibition and thus increases the likelihood of seizures. Here, using whole-cell (WC) and extracellular (EC) recordings as well as voltage-sensitive dye imaging (VSDI), we systematically searched for an in vivo correlate of cortical alterations caused by the G2R43Q mutation, as suggested by the mentioned in vitro results. We measured spontaneous and whisker-evoked activity in the primary somatosensory cortex and ventral posteriomedial nucleus of the thalamus (VPM) before and after intraperitoneal injection of the ictogenic substance pentylenetetrazol (PTZ) in urethane-anesthetized G2R43Q mice and controls in a blinded setting. Compared to wildtype controls in G2R43Q mice after PTZ injection we found 1.) Increased cortical spontaneous activity in layer 2/3 and layer 5/6 pyramidal neurons (increased standard deviation of the mean membrane potential in WC recordings), 2.) Increased variance of stimulus evoked cortical responses in VSDI experiments. 3.) The cortical effects are not due to increased strength or precision of thalamic output. In summary our findings support the hypothesis of a cortical pathology in this mouse model of human genetic absence epilepsy. Further study is needed to characterize underlying molecular mechanisms. PMID:25731747

  11. Delayed postnatal loss of P/Q type calcium channels recapitulates the absence epilepsy, dyskinesia, and ataxia phenotypes of genomic Cacna1A mutations

    PubMed Central

    Mark, Melanie D.; Maejima, Takashi; Kuckelsberg, Denise; Yoo, Jong W.; Hyde, Robert A.; Shah, Viral; Gutierrez, Davina; Moreno, Rosa L.; Kruse, Wolfgang; Noebels, Jeffrey L.; Herlitze, Stefan

    2011-01-01

    Inherited loss of P/Q-type calcium channel function causes human absence epilepsy, episodic dyskinesia, and ataxia, but the molecular ‘birthdate’ of the neurological syndrome and its dependence on prenatal pathophysiology is unknown. Since these channels mediate transmitter release at synapses throughout the brain and are expressed early in embryonic development, delineating the critical circuitry and onset underlying each of the emergent phenotypes requires targeted control of gene expression. To visualize P/Q-type Ca2+ channels and dissect their role in neuronal networks at distinct developmental stages, we created a novel conditional Cacna1a knock-in mouse by inserting the floxed GFP derivative Citrine into the first exon of Cacna1a, then crossing it with a postnatally expressing PCP2-Cre line for delayed Purkinje cell (PC) gene deletion within the cerebellum and sparsely in forebrain (purky). PCs in purky mice lacked P/Q-type calcium channel protein and currents within the first month after birth, displayed altered spontaneous firing, and showed impaired neurotransmission. Unexpectedly, adult purky mice exhibited the full spectrum of neurological deficits seen in mice with genomic Cacna1a ablation. Our results show that the ataxia, dyskinesia and absence epilepsy due to inherited disorders of the P/Q-type channel arise from signaling defects beginning in late infancy, revealing an early window of opportunity for therapeutic intervention. PMID:21411672

  12. Upregulated P2X3 Receptor Expression in Patients with Intractable Temporal Lobe Epilepsy and in a Rat Model of Epilepsy.

    PubMed

    Zhou, Xin; Ma, Li-Min; Xiong, Yan; Huang, Hao; Yuan, Jin-Xian; Li, Ruo-Han; Li, Jia-Ni; Chen, Yang-Mei

    2016-06-01

    Purinergic P2X3 receptors (P2X3Rs) play extensive roles in nerve cells in the central nervous system, particularly in hyperexcitability and calcium (Ca(2+)) influx. However, the role of P2X3Rs in epilepsy has not been previously investigated. To determine the relationship between P2X3Rs and epilepsy, the expression and cellular location of P2X3Rs in patients with intractable temporal lobe epilepsy (TLE) and in a lithium chloride-pilocarpine-induced chronic rat model of epilepsy were assessed. Furthermore, the function of P2X3Rs was assessed in vitro. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to evaluate the expression levels of P2X3Rs in brain tissues from TLE patients and an epileptic rat model, whereas immunofluorescence labeling was applied to determine the distribution of target proteins. Whole-cell recording was subsequently performed to identify the influence of P2X3Rs on seizure-like discharges. P2X3Rs were located at the cell bodies and dendrites of neurons with significantly increased expression in the TLE patients and epileptic rat model. In vitro, P2X3R activation accelerated sustained repetitive firing, whereas P2X3R inhibition led to relatively low-frequency discharges. To the best of our knowledge, this is the first study provide evidence that upregulated P2X3R expression exists in both epileptic humans and rats and may aggravate the epileptic state in vitro. Thus, P2X3Rs may represent a novel therapeutic target for antiepileptic drugs. PMID:26738991

  13. Role of neovibsanin scaffold in preservation of spatial cognitive functions of rats with chronic epilepsy

    PubMed Central

    Dong, Li-Quan; Yan, Li-Li; Pan, Xu-Dong; Hu, Jin-Hua; Zhang, Jun-Wei

    2015-01-01

    The effect of neovibsanin scaffold (NS) on the spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion was investigated. Rats were divided into long-term memory (LTM) and short-term memory (STM) groups with 15 rats in each group. The groups were subdivided into 3 groups: control group comprised of 5 rats without surgery, untreated group of 5 rats left without treatment after 2OV, and NS treatment group with 5 rats receiving 5 mg/kg daily for 12 weeks of 2VO operation. NS-treatment caused a marked decrease in the escape latency time and total distance travelled in the treatment group compared to untreated group which was evident from the working memory test. The animals of treatment group also showed significant improvement over that of untreated group in maze test performance. Furthermore, NS treatment also resulted in significant improvement in the probe memory test performance in treatment group compared to untreated group. These findings suggest that NS exhibits therapeutic effect on the spatial cognitive preservation in rats with chronic epilepsy. PMID:26339458

  14. Impairment of exploratory behavior and spatial memory in adolescent rats in lithium-pilocarpine model of temporal lobe epilepsy.

    PubMed

    Kalemenev, S V; Zubareva, O E; Frolova, E V; Sizov, V V; Lavrentyeva, V V; Lukomskaya, N Ya; Kim, K Kh; Zaitsev, A V; Magazanik, L G

    2015-01-01

    Cognitive impairment in six-week -old rats has been studied in the lithium-pilocarpine model of adolescent temporal lobe epilepsy in humans. The pilocarpine-treated rats (n =21) exhibited (a) a decreased exploratory activity in comparison with control rats (n = 20) in the open field (OP) test and (b) a slower extinction of exploratory behavior in repeated OP tests. The Morris Water Maze (MWM) test showed that the effect of training was less pronounced in the pilocarpine-treated rats, which demonstrated disruption of predominantly short-term memory. Therefore, our study has shown that lithium-pilocarpine seizures induce substantial changes in exploratory behavior and spatial memory in adolescent rats. OP and MWM tests can be used in the search of drugs reducing cognitive impairments associated with temporal lobe epilepsy. PMID:26335964

  15. Children with New Onset Epilepsy Exhibit Diffusion Abnormalities in Cerebral White Matter in the Absence of Volumetric Differences

    PubMed Central

    Hutchinson, Elizabeth; Pulsipher, Dalin; Dabbs, Kevin; Myers y Gutierrez, Adan; Sheth, Raj; Jones, Jana; Seidenberg, Michael; Meyerand, Elizabeth; Hermann, Bruce

    2010-01-01

    SUMMARY The purpose of this investigation was to examine the diffusion properties of cerebral white matter in children with recent onset epilepsy (n=19) compared to healthy controls (n=11). Subjects underwent DTI with quantification of mean diffusion (MD), fractional anisotropy (FA), axial diffusivity (Dax) and radial diffusivity (Drad) for regions of interest including anterior and posterior corpus callosum, fornix, cingulum, and internal and external capsules. Quantitative volumetrics were also performed for the corpus callosum and its subregions (anterior, midbody and posterior) and total lobar white and gray matter for the frontal, parietal, temporal and occipital lobes. The results demonstrated no group differences in total lobar gray or white matter volumes or volume of the corpus callosum and its subregions, but did show reduced FA and increased Drad in the posterior corpus callosum and cingulum. These results provide the earliest indication of microstructural abnormality in cerebral white matter among children with idiopathic epilepsies. This abnormality occurs in the context of normal volumetrics and suggests disruption in myelination processes. PMID:20044239

  16. Using ictal high-frequency oscillations (80-500Hz) to localize seizure onset zones in childhood absence epilepsy: a MEG study.

    PubMed

    Miao, Ailiang; Xiang, Jing; Tang, Lu; Ge, Huaiting; Liu, Hongxing; Wu, Ting; Chen, Qiqi; Hu, Zheng; Lu, Xiaopeng; Wang, Xiaoshan

    2014-04-30

    This study aimed to use ictal high-frequency oscillations (HFOs) ranging from 80Hz to 500Hz to locate seizure onset zones in childhood absence epilepsy (CAE) using non-invasive magnetoencephalography (MEG). Ten drug-naïve children with CAE were studied using a 275-channel MEG system. MEG data were digitized at a sampling rate of 6000Hz. HFO spectral power in real-time spectrograms was assessed using Morlet continuous wavelet transform. Magnetic sources were volumetrically localized through dynamic magnetic source imaging with a slide window. HFOs were identified in all patients. The total time of fast ripples (250-500Hz) was greater than that of ripples (80-250Hz) during absence seizures. The rate of fast ripples was associated with seizure frequency. HFO duration was significantly longer when co-occurring with spikes than when occurring independently, and the maximum frequency of HFOs co-occurring with spikes was higher than that of HFOs occurring independently. HFOs were predominantly localized in the medial prefrontal cortex (MPFC), whereas spikes were widespread to a variety of regions during the absence seizures. Compared with spikes, HFOs appeared to be more focal. The findings indicate that HFOs in the MPFC have a primary function in initializing epileptic activity in CAE. PMID:24582907

  17. Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model.

    PubMed

    Bercum, Florencia M; Rodgers, Krista M; Benison, Alex M; Smith, Zachariah Z; Taylor, Jeremy; Kornreich, Elise; Grabenstatter, Heidi L; Dudek, F Edward; Barth, Daniel S

    2015-12-01

    Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient. We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5. Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures. We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. PMID:26631470

  18. Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats

    PubMed Central

    Welting, Olaf; Cailotto, Cathy; Kalsbeek, Andries; van den Wijngaard, Rene

    2016-01-01

    Background: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity) is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS). In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur in shift work and trans meridian flights, are associated with the prevalence of IBS. This raises the question whether disruptions of circadian control are responsible for the observed pathology in IBS. Prior to investigating altered rhythmicity in relation to visceral hypersensitivity in a rat model for IBS, it is relevant to establish whether normal rats display circadian variation similar to healthy men.  Methodology and findings: In rodents colorectal distension leads to reproducible contractions of abdominal musculature. We used quantification of this so called visceromotor response (VMR) by electromyography (EMG) to assess visceral sensitivity in rats. We assessed the VMR in normal male Long Evans rats at different time points of the light/dark cycle. Although a control experiment with male maternal separated rats confirmed that intentionally inflicted (i.e. stress induced) changes in VMR can be detected, normal male Long Evans rats showed no variation in VMR along the light/dark cycle in response to colorectal distension. Conclusions: In the absence of a daily rhythm of colorectal sensitivity in normal control rats it is not possible to investigate possible aberrancies in our rat model for IBS. PMID:26925229

  19. Downregulation of gephyrin in temporal lobe epilepsy neurons in humans and a rat model.

    PubMed

    Fang, Min; Shen, Lan; Yin, Huan; Pan, Yu-Min; Wang, Liang; Chen, Dan; Xi, Zhi-Qin; Xiao, Zheng; Wang, Xue-Feng; Zhou, Sheng-Nian

    2011-10-01

    Gephyrin, which is a postsynaptic scaffolding protein participated in clustering GABA(A) receptors at inhibitory synapses, has been reported to be involved in temporal lobe epilepsy (TLE) recently. Here, we investigate gephyrin protein expression in the temporal lobe epileptic foci in epileptic patients and experimental animals in order to explore the probable relationship between gephyrin expression and TLE. Using immunohistochemistry, immunofluorescence, and western blot analysis, gephyrin expression was examined in 30 human temporal neocortex samples from patients who underwent surgery to treat drug-refractory TLE and 10 histological normal temporal neocortex from the controls. Meanwhile, we investigated the gephyrin expression in the hippocampus and adjacent neocortex from experimental rats on 24 h, 48 h, 1 week, 2 weeks, 1 month, and 2 months postseizure and from control rats. Gephyrin protein was mainly expressed in the membrane and cytoplasm of neurons in temporal lobe epileptic foci in humans and experimental rats. Gephyrin expression was significantly lower in the temporal neocortex of TLE patients compared to the controls. In experimental rats, the expression of gephyrin in temporal lobe was downregulated in epileptic groups compared to the control group. Gephyrin expression gradually decreased during the acute period and the latent period, but then began to increase below the levels seen in controls during the chronic phase. Our findings suggest that gephyrin may be involved in the development of TLE. PMID:21404332

  20. A new mode of corticothalamic transmission revealed in the Gria4–/– model of absence epilepsy

    PubMed Central

    Paz, Jeanne T.; Bryant, Astra S.; Peng, Kathy; Fenno, Lief; Yizhar, Ofer; Frankel, Wayne N.; Deisseroth, Karl; Huguenard, John R.

    2012-01-01

    Cortico-thalamo-cortical circuits mediate sensation and generate neural network oscillations associated with slow-wave sleep and various epilepsies. Cortical input to sensory thalamus is thought to mainly evoke feed-forward synaptic inhibition of thalamocortical (TC) cells via reticular thalamic nucleus (nRT) neurons, especially during oscillations. This relies on a stronger synaptic strength in the cortico-nRT pathway than in the cortico-TC pathway, allowing the feed-forward inhibition of TC cells to overcome direct cortico-TC excitation. We found a systemic and specific reduction in strength in GluA4-deficient (Gria4–/–) mice of one excitatory synapse of the rhythmogenic cortico-thalamo-cortical system, the cortico-nRT projection, and observed that the oscillations could still be initiated by cortical inputs via the cortico-TC-nRT-TC pathway. These results reveal a previously unknown mode of cortico-thalamo-cortical transmission, bypassing direct cortico-nRT excitation, and describe a mechanism for pathological oscillation generation. This mode could be active under other circumstances, representing a previously unknown channel of cortico-thalamo-cortical information processing. PMID:21857658

  1. Ketogenic Diet, but Not Polyunsaturated Fatty Acid Diet, Reduces Spontaneous Seizures in Juvenile Rats with Kainic Acid-induced Epilepsy

    PubMed Central

    Dustin, Simone M.; Stafstrom, Carl E.

    2016-01-01

    Background and Purpose: The high-fat, low-carbohydrate ketogenic diet (KD) is effective in many cases of drug-resistant epilepsy, particularly in children. In the classic KD, fats consist primarily of long-chain saturated triglycerides. Polyunsaturated fatty acids (PUFAs), especially the n-3 type, decrease neuronal excitability and provide neuroprotection; pilot human studies have raised the possibility of using PUFAs to control seizures in patients. Methods: To determine the relative roles of the KD and PUFAs in an animal model, we induced epilepsy in juvenile rats (P29–35) using intraperitoneal kainic acid (KA). KA caused status epilepticus in all rats. Two days after KA, rats were randomized to one of 4 dietary groups: Control diet; PUFA diet; KD; or KD plus PUFA. All diets were administered isocalorically at 90% of the rat recommended daily calorie requirement. Spontaneous recurrent seizures (SRS) were assessed for 3 months after diet randomization. Results: Rats receiving the KD or KD-PUFA diet had significantly fewer SRS than those receiving the Control diet or PUFA diet. The PUFA diet did not reduce SRS compared to the Control diet. Conclusions: In the KA epilepsy model, the KD protects against SRS occurrence but dietary enhancement with PUFA does not afford additional protection against spontaneous seizures. PMID:27390673

  2. High dosage of cannabidiol (CBD) alleviates pentylenetetrazole-induced epilepsy in rats by exerting an anticonvulsive effect.

    PubMed

    Mao, Ke; You, Chao; Lei, Ding; Zhang, Heng

    2015-01-01

    The study was designed to investigate the effect of various concentrations of cannabidiol (CBD) in rats with chronic epilepsy. The chronic epilepsy rat model was prepared by intraperitoneally injecting pentylenetetrazole to the rats pre-treated with CBD (10, 20 and 50 mg/kg) for 28 consecutive days. Behavioral measurements of convulsion following pentylenetetrazole treatment and morphological changes of the hippocampal neurons with hematoxylin and eosin staining were used to observe the epileptic behaviour. Immunohistochemistry was used to detect the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus. The mRNA expression of N-methyl-D-aspartic acid (NMDA) receptor subunits (NR1 and NR2B) was detected by reverse transcription polymerase chain reaction. The results revealed a significant decrease in the daily average grade of epileptic seizures on treatment with CBD (50 mg/kg). The neuronal loss and astrocyte hyperplasia in the hippocampal area were also decreased. CBD treatment did not affect the expression of iNOS in the hippocampus; however, the expression of NR1 was decreased significantly. Thus, CBD administration inhibited the effect of pentylenetetrazole in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Therefore, CBD exhibits an anticonvulsive effect in the rats with chronic epilepsy. PMID:26309534

  3. Etiology matters – Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy

    PubMed Central

    Dębski, Konrad J.; Pitkanen, Asla; Puhakka, Noora; Bot, Anna M.; Khurana, Ishant; Harikrishnan, KN; Ziemann, Mark; Kaspi, Antony; El-Osta, Assam; Lukasiuk, Katarzyna; Kobow, Katja

    2016-01-01

    This study tested the hypothesis that acquired epileptogenesis is accompanied by DNA methylation changes independent of etiology. We investigated DNA methylation and gene expression in the hippocampal CA3/dentate gyrus fields at 3 months following epileptogenic injury in three experimental models of epilepsy: focal amygdala stimulation, systemic pilocarpine injection, or lateral fluid-percussion induced traumatic brain injury (TBI) in rats. In the models studies, DNA methylation and gene expression profiles distinguished controls from injured animals. We observed consistent increased methylation in gene bodies and hypomethylation at non-genic regions. We did not find a common methylation signature in all three different models and few regions common to any two models. Our data provide evidence that genome-wide alteration of DNA methylation signatures is a general pathomechanism associated with epileptogenesis and epilepsy in experimental animal models, but the broad pathophysiological differences between models (i.e. pilocarpine, amygdala stimulation, and post-TBI) are reflected in distinct etiology-dependent DNA methylation patterns. PMID:27157830

  4. Amiloride and SN-6 Suppress Audiogenic Seizure Susceptibility in Genetically Epilepsy-Prone Rats

    PubMed Central

    Quansah, Hillary; N’Gouemo, Prosper

    2015-01-01

    SUMMARY Aims We have recently reported that amiloride, a potent and nonselective blocker of acid-sensing ion channels, prevents the development of pilocarpine-induced seizures and status epilepticus. Amiloride is also known to suppress the activity of Na+/Ca2+ and Na+/H+ exchangers that have been implicated in the pathophysiology of seizures. Here, we evaluated the effects of amiloride, SN-6 (a potent blocker of Na+/Ca2+ exchangers) and zoniporide (a potent blocker of Na+/H+ exchangers) on acoustically evoked seizures (audiogenic seizures, AGS) in genetically epilepsy-prone rats (GEPR-3s), a model of inherited generalized epilepsy. Methods Male, six-week-old GEPR-3s were used. The GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of amiloride, SN-6, and zoniporide (1, 3, 10, and 30 mg/kg; per os). Results We found that pretreatment with amiloride and SN-6 markedly reduced the incidence and severity of AGS in the GEPR-3s. In contrast, administration of zoniporide only minimally reduced the incidence and severity of AGS in the GEPR-3s. A combination of noneffective doses of SN-6 and zoniporide also suppressed AGS susceptibility in the GEPR-3s. Conclusions These findings suggest acid-sensing ion channels and the Na+/Ca2+ exchanger may play an important role in the pathophysiology of inherited AGS susceptibility in the GEPR-3s. PMID:24948133

  5. Absence of a 23 KD protein in testes of testicular ferminization rat

    SciTech Connect

    Chan, W.Y.; Bates, J.M. Jr.; Rennert, O.M.; Chung, K.W.

    1987-06-01

    Cryptorchid testes of testicular ferminization rats are very low in zinc in spite of normal zinc status of the animals. Analysis of the cytosol of the cryptorchid testes by gel permeation chromatography showed decreased zinc binding by proteins eluted at fractions corresponding to 30,000 dalton. Further analysis by sodium dodecylsulphate polyacrylamide gel electrophoresis indicated the absence of a protein with molecular weigh of 23,000. 36 references, 2 figures.

  6. Interaction of flunarizine with sodium valproate or ethosuximide in gamahydroxybutyrate induced absence seizures in rats.

    PubMed

    Subramanyam, K; David, J; Joseph, T

    2001-10-01

    Sodium valproate(VPA), ethosuximide(ESM), 200 mg/kg ip and flunarizine (FLU) 5 or 10 mg/kg ip were first administered independently to rats in order to study their effects on behavioural and EEG aspects of spike and wave discharges (SWDs) induced by y- hydroxybutyrate (GHB,100 mg/kg ip). GHB treated rats show behavioural changes and concomitant repetitive EEG episodes of 7 to 9 Hz SWDs, mimicking human absence seizures (AS), and can be used as a pharmacological model. The number and duration of SWDs were calculated for 1 hr from the EEG and were parameters for drug evaluation. VPA and ESM at 200 mg/kg, significantly reduced SWD number and duration/hr, while FLU showed significant reduction only at 10 but not at 5 mg/kg. Combination of FLU, 10 mg/kg with either VPA or ESM showed significant reduction of SWD number and duration, suggesting an additive effect of the anti-absence agents with the calcium channel blocker, FLU, on experimental absence seizures in rats. PMID:11883524

  7. Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids.

    PubMed

    Cysneiros, Roberta M; Ferrari, Danuza; Arida, Ricardo M; Terra, Vera C; de Almeida, Antonio-Carlos G; Cavalheiro, Esper A; Scorza, Fulvio A

    2010-01-01

    Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy. PMID:19969506

  8. Impact of Injury Location and Severity on Posttraumatic Epilepsy in the Rat: Role of Frontal Neocortex

    PubMed Central

    Curia, Giulia; Levitt, Michael; Fender, Jason S.; Miller, John W.; Ojemann, Jeffrey

    2011-01-01

    Human posttraumatic epilepsy (PTE) is highly heterogeneous, ranging from mild remitting to progressive disabling forms. PTE results in simple partial, complex partial, and secondarily generalized seizures with a wide spectrum of durations and semiologies. PTE variability is thought to depend on the heterogeneity of head injury and patient's age, gender, and genetic background. To better understand the role of these factors, we investigated the seizures resulting from calibrated fluid percussion injury (FPI) to adolescent male Sprague–Dawley rats with video electrocorticography. We show that PTE incidence and the frequency and severity of chronic seizures depend on the location and severity of FPI. The frontal neocortex was more prone to epileptogenesis than the parietal and occipital, generating earlier, longer, and more frequent partial seizures. A prominent limbic focus developed in most animals, regardless of parameters of injury. Remarkably, even with carefully controlled injury parameters, including type, severity, and location, the duration of posttraumatic apnea and the age and gender of outbred rats, there was great subject-to-subject variability in frequency, duration, and rate of progression of seizures, indicating that other factors, likely the subjects' genetic background and physiological states, have critical roles in determining the characteristics of PTE. PMID:21112931

  9. Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy.

    PubMed

    Doná, Flávia; Conceição, Isaltino Marcelo; Ulrich, Henning; Ribeiro, Eliane Beraldi; Freitas, Thalma Ariani; Nencioni, Ana Leonor Abrahao; da Silva Fernandes, Maria José

    2016-06-01

    Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy. PMID:26939579

  10. [An overview of epilepsy: its history, classification, pathophysiology and management].

    PubMed

    Hirose, Genjiro

    2013-05-01

    Epilepsy, a common chronic set of neurological disorders characterized by seizures, affects more than 50 million people worldwide. In fact, it is estimated that the annual incidence of new onset epilepsy in the general population is more than 80 per 100,000, occurring mostly in children and the elderly. Epilepsy is not a single specific disease, or even a single syndrome, but rather a broad category of symptom complexes arising from any number of disordered brain functions. The history of epilepsy dates back to a time when it was associated with religious experiences and even demonic possession; textbooks from the Babylonian Era (718-612 BC) emphasize the supernatural nature of epilepsy, while in ancient Greece, Hippocrates described it as the "Sacred Disease". Our modern understanding of epilepsy as a neurological disorder associated with seizures only originated in the mid-19th century through the research of John Hughlings-Jackson. Classification of epilepsies, epileptic syndromes, and related seizure disorders first appeared 1981 and later in 1989, as described by the International League Against Epilepsy (ILAE). Newer classifications have since been proposed by the same organization; however, these are still rather controversial and have not yet been accepted worldwide. The pathophysiology of epilepsy, including the pharmacological and neurophysiological aspects, has been studied extensively. Epileptogenicity is induced by abnormal cellular excitability that arises from depolarization and hyperpolarization events, as well as from aberrant neuronal networks that develop abnormal synchronization. These events can be studied using mutant epileptogenic animals, such as the GAERS rat model of absence epilepsy. The past 15 years has seen the development of many new drugs for the treatment of epilepsy, thus providing a diverse choice for epileptologists and their patients. However, a better understanding of these drugs is required to improve the therapeutic

  11. [Typological features of behavior and memory in Norway rats selected for absence of aggression toward a man].

    PubMed

    Loskutova, L V; Dubrovina, N I; Pliusnina, I F

    2003-01-01

    Features of behavior and retrieval of passive conditioned avoidance on a new and forgotten stimuli were compared in Wistar rats and Norway rats bred for the absence of aggression toward a man. As distinct from white rats, grey rats were characterized by low anxiety and high locomotor exploratory activity in the elevated plus maze and dark-light chamber. Norway rats demonstrated better avoidance performance with active defensive behavioral strategy than Wistar rats. Latent inhibition during conditioning with a previously forgotten situational stimulus was the same in both rat strains. The results are discussed in terms of the use of grey rats as a model for an in-depth analysis of the mechanisms of memory optimization. PMID:14959488

  12. SWDreader: A Wavelet-Based Algorithm Using Spectral Phase to Characterize Spike-Wave Morphological Variation in Genetic Models of Absence Epilepsy

    PubMed Central

    Richard, CD; Tanenbaum, A; Audit, B; Arneodo, A; Khalil, A; Frankel, WN

    2014-01-01

    Background Spike-wave discharges (SWD) found in neuroelectrical recordings are pathognomonic to absence epilepsy. The characteristic spike-wave morphology of the spike-wave complex (SWC) constituents of SWDs can be mathematically described by a subset of possible spectral power and phase values. Morlet wavelet transform (MWT) generates time-frequency representations well-suited to identifying this SWC-associated subset. New method MWT decompositions of SWDs reveal spectral power concentrated at harmonic frequencies. The phase relationships underlying SWC morphology were identified by calculating the differences between phase values at SWD fundamental frequency and the 2nd, 3rd and 4th harmonics. The three phase differences were then used as coordinates to generate a density distribution in a {360° × 360° × 360°} phase difference space. Strain-specific density distributions were generated from SWDs of mice carrying the Gria4, Gabrg2 or Scn8a mutations to determine whether SWC morphological variants reliably mapped to the same regions of the distribution, and if distribution values could be used to detect SWD. Comparison with existing methods To the best of our knowledge, this algorithm is the first to employ spectral phase to quantify SWC morphology, making it possible to computationally distinguish SWC subtypes and detect SWDs. Results/conclusions Proof-of-concept testing of the SWDreader algorithm shows: (1) a major pattern of variation in SWC morphology maps to one axis of the phase difference distribution, (2) variability between the strain-specific distributions reflects differences in the proportion of SWC subtypes generated during SWD, and (3) regularities in the spectral power and phase profiles of SWCs can be used to detect waveforms possessing SWC-like morphology. PMID:25549550

  13. Beyond the information (not) given: Representations of stimulus absence in rats (Rattus norvegicus).

    PubMed

    Dwyer, Dominic M; Waldmann, Michael R

    2016-08-01

    Questions regarding the nature of nonhuman cognition continue to be of great interest within cognitive science and biology. However, progress in characterizing the relative contribution of "simple" associative and more "complex" reasoning mechanisms has been painfully slow-something that the tendency for researchers from different intellectual traditions to work separately has only exacerbated. This article reexamines evidence that rats respond differently to the nonpresentation of an event than they do if the physical location of that event is covered. One class of explanation for the sensitivity to different types of event absence is that rats' representations go beyond their immediate sensory experience and that covering creates uncertainty regarding the status of an event (thus impacting on the underlying causal model of the relationship between events). A second class of explanation, which includes associative mechanisms, assumes that rats represent only their direct sensory experience and that particular features of the covering procedures provide incidental cues that elicit the observed behaviors. We outline a set of consensus predictions from these two classes of explanation focusing on the potential importance of uncertainty about the presentation of an outcome. The example of covering the food-magazine during the extinction of appetitive conditioning is used as a test case for the derivation of diagnostic tests that are not biased by preconceived assumptions about the nature of animal cognition. (PsycINFO Database Record PMID:27512823

  14. Posttraumatic seizures and epilepsy in adult rats after controlled cortical impact.

    PubMed

    Kelly, Kevin M; Miller, Eric R; Lepsveridze, Eka; Kharlamov, Elena A; Mchedlishvili, Zakaria

    2015-11-01

    Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. Provoked class 3-5 seizures were recorded by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI of the right parietal cortex; none of the 7 animals demonstrated subsequent spontaneous convulsive seizures. Monitoring with video and/or video-EEG was performed on 128 animals at various time points 8-619 days beyond one week following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in 7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually characterized by an initial change in behavior (head raising or animal alerting) followed by motor arrest during an ictal discharge that consisted of high-amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz class 3-5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI-injured, 13 controls) underwent transcardial perfusion for gross and microscopic studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure-function relationships that underlie epileptogenesis and PTE. PMID

  15. Absence epilepsy and the CHD2 gene: an adolescent male with moderate intellectual disability, short-lasting psychoses, and an interstitial deletion in 15q26.1–q26.2

    PubMed Central

    Verhoeven, Willem MA; Egger, Jos IM; Knegt, Alida C; Zuydam, José; Kleefstra, Tjitske

    2016-01-01

    Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2) gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations) and DECIPHER (database of genomic variation and phenotype in humans using ensembl resources), so far, a total of 13 intellectually disabled patients with a genetically proven deletion of the CHD2 gene are described, of whom eleven had a history of severe forms of epilepsy starting from a young age. In this article, a moderately intellectually disabled 15-year-old male with a 15q26.1–q26.2 interstitial deletion is reported, who was referred for analysis of two recent short-lasting psychotic episodes that were nonresponsive to antipsychotic treatment and recurrent disinhibited behaviors since early infancy. Careful interdisciplinary assessment revealed that the psychotic phenomena originated from a previously unrecognized absence epilepsy. Treatment with valproic acid was started which resulted in full remission of psychotic symptoms, and consequently, substantial improvement of behavior. It was concluded that in case of (rare) developmental disorders with genetically proven etiology, a detailed inventory of anamnestic data and description of symptomatology over time may elucidate epilepsy-related psychopathology for which a specific treatment regimen is needed. PMID:27274247

  16. Animal models to study aetiopathology of epilepsy: what are the features to model?

    PubMed

    Guillemain, Isabelle; Kahane, Philippe; Depaulis, Antoine

    2012-09-01

    In order to understand the physiopathology of epilepsies and develop antiepileptic drugs, animal models have been developed. These models appear to be valuable predictors of treatment efficacy; however, several of the currently used models remain questionable and probably inappropriate for the search for new treatments, in particular for epilepsies that cannot be treated by current antiepileptic drugs. In the present review, we report the results of a recent survey conducted by neurologists in charge of an epilepsy programme based at different hospitals in France. The 36 experts were questioned, via the internet, on the most critical features of four prototypic forms of epilepsy (idiopathic generalised epilepsies with convulsive seizures, absence epilepsy, focal epilepsy associated with dysplasia, and focal epilepsy associated with hippocampal sclerosis) that should be taken into account with regards to the relevance of animal models of epilepsy. Their answers suggest that most current models for focal epilepsies associated with either dysplasia or hippocampal sclerosis do not address the most relevant features. The models currently used in mice and rats are discussed in light of the data obtained in our survey. PMID:22947423

  17. Absence of cue-evoked firing in rat dorsolateral striatum neurons

    PubMed Central

    Root, David H.; Tang, Chris C.; Ma, Sisi; Pawlak, Anthony P.; West, Mark O.

    2010-01-01

    The rat dorsolateral striatum (DLS) has been implicated in habit formation. Previous studies in our laboratory found that as animals acquired a motor habit or remained goal-directed, tested by reward devaluation, the vast majority of DLS neurons decreased firing rates during the same responses over training days. However, mixed results have been reported in the literature regarding whether DLS neurons exhibit cue-reactivity. In the present study, we reanalyzed a sample of DLS head movement neurons in a task in which habitual behavior was acquired (dataset of Tang et al, 2007) and found that somatic sensorimotor as well as nonsomatomotor neurons of the DLS exhibited no cue-evoked firing. A second sample of DLS neurons related to licking in a task in which goal-directed behavior occurred (dataset of Tang et al, 2009) was also reanalyzed for cue-evoked correlates. Although behavior was cue-guided, lick neurons did not exhibit cue-evoked firing. Given the complete absence of cue-related firing during habitual or goal-directed behavior, adaptations in DLS firing patterns may be regulated by movement-related learning rather than nonsomatosensory cues, consistent with convergent S1 and M1 afferents to the region. Striatal cue reactivity in the rat is likely mediated within the dorsomedial and ventromedial striatum, in line with associative and limbic afferents to these regions, respectively. PMID:20211654

  18. A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat

    PubMed Central

    Pérès, Isabelle A. A.; Hadid, Rebecca D.; Amada, Naoki; Hill, Charlotte; Williams, Claire; Stanford, Ian M.; Morris, Christopher M.; Jones, Roland S. G.; Whalley, Benjamin J.; Woodhall, Gavin L.

    2016-01-01

    Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles. PMID:26909803

  19. A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat.

    PubMed

    Modebadze, Tamara; Morgan, Nicola H; Pérès, Isabelle A A; Hadid, Rebecca D; Amada, Naoki; Hill, Charlotte; Williams, Claire; Stanford, Ian M; Morris, Christopher M; Jones, Roland S G; Whalley, Benjamin J; Woodhall, Gavin L

    2016-01-01

    Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model's features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles. PMID:26909803

  20. A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy.

    PubMed Central

    Rashid, K; Van der Zee, C E; Ross, G M; Chapman, C A; Stanisz, J; Riopelle, R J; Racine, R J; Fahnestock, M

    1995-01-01

    Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization. Images Fig. 2 PMID:7568161

  1. Chronic treatment with levetiracetam reverses deficits in hippocampal LTP in vivo in experimental temporal lobe epilepsy rats.

    PubMed

    Ge, Yu-Xing; Tian, Xiang-Zhu; Lin, Ying-Ying; Liu, Xue-Yuan

    2016-08-15

    Temporal lobe epilepsy (TLE), the common form of epilepsy in adults, often displays complex partial seizures and cognitive deficits. The underlying mechanisms of such deficits are not yet well understood. Many contributing factors, such as initial epileptogenic lesion, seizure type, age of onset, and treatment side effects have been proposed. Levetiracetam (LEV) is a novel anti-epileptic drug (AED) used to treat partial seizures and idiopathic generalized epilepsy. It has been suggested that LEV exerts antiepileptic properties by modulation of synaptic release of neurotransmitters. However, its neuroprotective effects on learning and memory are not yet well demonstrated. Here we showed the impairment of spatial memory in the pilocarpine-induced experimental TLE rats, which can be improved by LEV. Furthermore, we found chronic LEV treatment partially reversed the SE-induced synaptic dysfunction in hippocampal LTP induction in vivo. In addition, LEV treatment can alleviate the SE-induced abnormal GluR1 phosphorylation at Ser(831) site, which may contribute to the rescue of synaptic transmission. These results indicate the neuroprotective role for LEV while it exhibits an antiseizure effect on experimental epileptic models. PMID:27345386

  2. Xenograft of human umbilical mesenchymal stem cells from Wharton's jelly as a potential therapy for rat pilocarpine-induced epilepsy.

    PubMed

    Huang, Pei-Yu; Shih, Yang-Hsin; Tseng, Yi-jhan; Ko, Tsui-Ling; Fu, Yu-Show; Lin, Yung-Yang

    2016-05-01

    We evaluated the effects of intra-hippocampal transplantation of human umbilical mesenchymal stem cells (HUMSCs) on pilocarpine-treated rats. Sprague-Dawley rats were divided into the following three groups: (1) a normal group of rats receiving only PBS, (2) a status epilepticus (SE) group of rats with pilocarpine-induced SE and PBS injected into the hippocampi, and (3) a SE+HUMSC group of SE rats with HUMSC transplantation. Spontaneous recurrent motor seizures (SRMS) were monitored using simultaneous video and electroencephalographic recordings at two to four weeks after SE induction. The results showed that the number of SRMS within two to four weeks after SE was significantly decreased in SE+HUMSCs rats compared with SE rats. All of the rats were sacrificed on Day 29 after SE. Hippocampal morphology and volume were evaluated using Nissl staining and magnetic resonance imaging. The results showed that the volume of the dorsal hippocampus was smaller in SE rats compared with normal and SE+HUMSCs rats. The pyramidal neuron loss in CA1 and CA3 regions was more severe in the SE rats than in normal and SE+HUMSCs rats. No significant differences were found in the hippocampal neuronal loss or in the number of dentate GABAergic neurons between normal and SE+HUMSCs rats. Compared with the SE rats, the SE+HUMSCs rats exhibited a suppression of astrocyte activity and aberrant mossy fiber sprouting. Implanted HUMSCs survived in the hippocampus and released cytokines, including FGF-6, amphiregulin, glucocorticoid-induced tumor necrosis factors receptor (GITR), MIP-3β, and osteoprotegerin. In an in vitro study, exposure of cortical neurons to glutamate showed a significant decrease in cell viability, which was preventable by co-culturing with HUMSCs. Above all, the expression of human osteoprotegerin and amphiregulin were significantly increased in the media of the co-culture of neurons and HUMSCs. Our results demonstrate the therapeutic benefits of HUMSC transplantation for

  3. Reorganization of supramammillary-hippocampal pathways in the rat pilocarpine model of temporal lobe epilepsy: evidence for axon terminal sprouting.

    PubMed

    Soussi, Rabia; Boulland, Jean-Luc; Bassot, Emilie; Bras, Hélène; Coulon, Patrice; Chaudhry, Farrukh Abbas; Storm-Mathisen, Jon; Ferhat, Lotfi; Esclapez, Monique

    2015-07-01

    In mesial temporal lobe epilepsy (MTLE), spontaneous seizures likely originate from a multi-structural epileptogenic zone, including several regions of the limbic system connected to the hippocampal formation. In this study, we investigate the structural connectivity between the supramammillary nucleus (SuM) and the dentate gyrus (DG) in the model of MTLE induced by pilocarpine in the rat. This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE. Our findings demonstrate a marked reorganization of DG afferents originating from the SuM in pilocarpine-treated rats. This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy. It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG. This reorganization, which reflects an axon terminal sprouting from SuM neurons, could contribute to trigger spontaneous seizures within an altered hippocampal intrinsic circuitry. PMID:24889162

  4. Enriched Environment Altered Aberrant Hippocampal Neurogenesis and Improved Long-Term Consequences After Temporal Lobe Epilepsy in Adult Rats.

    PubMed

    Zhang, Xiaoqian; Liu, Tingting; Zhou, Zhike; Mu, Xiaopeng; Song, Chengguang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

    2015-06-01

    Abnormal hippocampal neurogenesis is thought to contribute to cognitive impairments in chronic temporal lobe epilepsy (TLE). Stromal cell-derived factor-1 (SDF-1) and its specific receptor CXCR4 play important roles in neurogenesis. We investigated whether enriched environment (EE) might be beneficial for TLE. Adult rats were randomly assigned as control rats, rats subjected to status epilepticus (SE), or post-SE rats treated with EE for 30 days. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze. Western blot was used to measure the expression of SDF-1 and CXCR4 in the hippocampus. In the present study, we found the TLE model resulted in aberrant neurogenesis such as reduced proliferation, intensified dendritic development of newborn neurons, as well as spontaneous seizures and cognitive impairments. More importantly, EE treatment significantly increased the cell proliferation and survival, extended the apical dendrites, and delayed the attenuation of the expression of SDF-1 and CXCR4, accompanied by decreased long-term seizure activity and improved cognitive impairments in adult rats after TLE. These results provided morphological evidence that EE might be beneficial for treating TLE. PMID:25946980

  5. Involvement of upregulation of miR-210 in a rat epilepsy model

    PubMed Central

    Chen, Licheng; Zheng, Hao; Zhang, Shimeng

    2016-01-01

    Epilepsy is a common type of neurological disorder with complex etiology. The mechanisms are still not clear. MicroRNAs are endogenous noncoding RNAs with many physiological activities. Multiple microRNAs were abnormally expressed in status epilepticus, including miR-210. In this study, we applied lithium chloride and pilocarpine to induce epileptic activity and aimed to disclose the potential mechanisms. Our data showed that miR-210 was significantly upregulated in hippocampus one day after modeling (P<0.05 vs control) and the high expression of miR-210 lasted for at least 30 days. By contrast, γ-aminobutyric acid (GABA) level significantly decreased concurrently after modeling (P<0.05 vs control). To question whether miR-210 could be a potential therapeutic target for epilepsy, miR-210 inhibitor was administrated through intrahippocampal injection after epilepsy modeling. Our data showed that morphological changes of hippocampal neurons and apoptosis triggered by epilepsy were mitigated by miR-210 inhibition. More importantly, the expressions of GABA-related proteins, including GABAA receptor α1, glutamate decarboxylase, and GABA transporter 1, were significantly elevated after epilepsy modeling in both mRNA and protein levels 3 days postmodeling (P<0.05 vs control), which were mitigated by miR-210 inhibitor treatment (P<0.05 vs model). In addition, epilepsy-induced upregulation of GABA transaminase was alleviated by miR-210 inhibitor. Taken together, these data implicated potential roles of miR-210 in lithium chloride–pilocarpine-induced epilepsy model and miR-210 could serve as a potential therapeutic target in status epilepticus. PMID:27471387

  6. Absence of reactive intermediates in the formation of catechol estrogens by rat liver microsomes.

    PubMed

    Jellinck, P H; Hahn, E F; Fishman, J

    1986-06-15

    Release of 3H2O from regiospecifically labeled estradiol was measured during 2-hydroxylation of this estrogen by rat liver microsomes. The amount of tritium remaining in the isolated catechol estrogen was also determined. Virtually all the tritium was removed from C-2 during the reaction confirming the absence of an NIH shift. About 20% of the tritium at C-1 was also lost without any such change occurring at C-4 or C-6,7 of the steroid molecule. These findings provide evidence for the formation of an arene oxide or o-semiquinone intermediate during the conversion of estradiol to 2-hydroxyestradiol. No indication of adduct formation at either C-1 or C-4 during this biotransformation was obtained although the 2-hydroxylated product was able to react with a nucleophile such as glutathione. The different regiospecificity of tritium loss in the generation of catechol estrogens and in their subsequent reaction leads to the important conclusion that the reactive intermediates in the two processes must be different. The possible role of catechol estrogens in neoplastic transformation is discussed. PMID:3011797

  7. Decreased glutamine synthetase, increased citrulline-nitric oxide cycle activities, and oxidative stress in different regions of brain in epilepsy rat model.

    PubMed

    Swamy, Mummedy; Yusof, Wan Roslina Wan; Sirajudeen, K N S; Mustapha, Zulkarnain; Govindasamy, Chandran

    2011-03-01

    To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2 h and the long term (chronic) group animals were killed after 5 days of single injection of KA (15 mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy. PMID:20960085

  8. Epilepsy - resources

    MedlinePlus

    Resources - epilepsy ... The following organizations are good resources for information on epilepsy : Epilepsy Foundation -- www.efa.org National Institute of Neurologic Disorders and Stroke -- www.ninds.nih.gov/disorders/ ...

  9. Common pediatric epilepsy syndromes.

    PubMed

    Park, Jun T; Shahid, Asim M; Jammoul, Adham

    2015-02-01

    Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common epilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly encountered. BRE remits by age 16 years with many children requiring no treatment. Seizures in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also present with seizures that are self-limited with no associated psychomotor disturbances. Benign familial neonatal convulsions caused by a channelopathy, and inherited in an autosomal dominant manner, have a favorable outcome with spontaneous resolution. Benign idiopathic neonatal seizures, also referred to as "fifth-day fits," are an example of another epilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy are characterized as "benign" idiopathic age-related epilepsies as they have favorable implications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, and have no associated psychomotor disturbances. However, sometimes selected patients may have associated comorbidities such as cognitive and language delay for which the term "benign" may not be appropriate. PMID:25658216

  10. Genetic threshold hypothesis of neocortical spike-and-wave discharges in the rat: An animal model of petit mal epilepsy

    SciTech Connect

    Vadasz, C.; Fleischer, A.; Carpi, D.; Jando, G.

    1995-02-27

    Neocortical high-voltage spike-and-wave discharges (HVS) in the rat are an animal model of petit mal epilepsy. Genetic analysis of total duration of HVS (s/12 hr) in reciprocal F1 and F2 hybrids of F344 and BN rats indicated that the phenotypic variability of HVS cannot be explained by simple, monogenic Mendelian model. Biometrical analysis suggested the presence of additive, dominance, and sex-linked-epistatic effects, buffering maternal influence, and heterosis. High correlation was observed between average duration (s/episode) and frequency of occurrence of spike-and-wave episodes (n/12 hr) in parental and segregating generations, indicating that common genes affect both duration and frequency of the spike-and-wave pattern. We propose that both genetic and developmental - environmental factors control an underlying quantitative variable, which, above a certain threshold level, precipitates HVS discharges. These findings, together with the recent availability of rat DNA markers for total genome mapping, pave the way to the identification of genes that control the susceptibility of the brain to spike-and-wave discharges. 67 refs., 3 figs., 5 tabs.

  11. Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy

    PubMed Central

    Campbell, John N.; Gandhi, Anandh; Singh, Baljinderjit; Churn, Severn B.

    2014-01-01

    Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later. PMID:25580467

  12. Decreased expression of Ras-GRF1 in the brain tissue of the intractable epilepsy patients and experimental rats.

    PubMed

    Zhu, Qiong; Wang, Liang; Xiao, Zheng; Xiao, Fei; Luo, Jing; Zhang, Xiaogang; Peng, Xi; Wang, Xuefeng; Sun, Hongbin

    2013-02-01

    Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) is present mainly at synaptosome and its expression after birth increases in parallel with the development of neuronal circuitry. Evidences suggested that Ras-GRF1 could mediate forms of synaptic plasticity and might participate in the regulation of neuronal excitability and neurite outgrowth though various signal transduction pathway. The aim of this study was to measure Ras-GRF1 expression in brain tissue of patients with drug-refractory temporal lobe epilepsy (TLE) and lithium chloride-pilocarprine kindled rats using double-label immunofluorescence, immunohistochemistry and Western blotting and to discuss the possible role of Ras-GRF1 in TLE. We randomly selected 30 temporal neocortices tissues from patients with TLE and 9 histologically normal temporal neocortices samples from controls. Meanwhile, we investigated the distribution and level of Ras-GRF1 protein expression during the different phases (the acute period, the latent period and the chronic phase) in the epileptic and control rats. Ras-GRF1 was mainly expressed in the plasma membrane and dendrite of neurons, but it was not co-expressed with GFAP-positive astrocytes in the brain tissue of patients and epileptic rats. Compared with controls, Ras-GRF1 expression was significantly decreased in TLE patients. Ras-GRF1 expression in epileptic rats was already reduced at 1 day post-seizures, then gradually decreased during the latent period and reached a minimum level during the chronic phase. These results demonstrated that the decreased expression of Ras-GRF1 could be involved in the pathogenesis of human TLE. PMID:23200899

  13. Changes during pentetrazol-induced epilepsy in rat recorded by simultaneous EEG/MRI at 7T

    NASA Astrophysics Data System (ADS)

    Verhoye, Marleen; Michiels, Ive; Sijbers, Jan; Eelen, Jan; Peeters, Ronald; Van Audekerke, Johan; D'hooge, Rudi; De Deyn, P. P.; Van der Linden, Anne-Marie

    2000-04-01

    Simultaneously acquired EEG and BOLD (Blood Oxygenation level dependent contrast) MRI allowed to study on line the neurophysiological changes in rat brain during epileptic seizures. MRI and EEG data were acquired with a specially designed high quality MR RF-antenna with incorporated non- invasive carbon EEG electrodes. The problem of severe pollution of the EEG data due to MR gradient switching during simultaneous EEG/MRI acquisitions was solved by a specially designed automated effective filtering algorithm. We measured continuously EEG data, and T2*-weighted coronal MRI sections of rat brain before and after the injection of pentetrazol (43 mg/(kg body weight) PTZ; convulsive dose 97%), an epilepsy inductor. In this way, we could correlate the abnormalities in the EEG traces, with changes in the MRI BOLD signal intensities. Immediately after PTZ induction and before epileptic discharges were observed on the EEG traces, the cortex displayed an increase in BOLD signal intensity (increase in blood flow). Much later and correlated with epileptic discharges on the EEG traces, the ventromedial hypothalamic nuclei showed an increased BOLD signal while the BOLD signal intensity dropped in the entire brain, except for the hypothalamus. The decreased BOLD signal reflected general hypoxia and subsequent ischemia as a consequence of the sustained depolarization of neurons during the seizure.

  14. A novel detachable head-mounted device for simultaneous EEG and photoacoustic monitoring of epilepsy in freely moving rats.

    PubMed

    Wang, Bo; Zhou, Junli; Carney, Paul; Jiang, Huabei

    2015-02-01

    The study of neuro-hemodynamic changes in freely moving animals provides for a better understanding of brain dynamics in normal and disease states. While it has been shown that hemodynamic changes are closely related to seizures, methods for detection in freely moving animals are limited. In this work, we integrate photoacoustic sensor technology and electroencephalography into a small portable device that can be attached on the head of wake freely moving animals. We demonstrate chronic simultaneous monitoring of photoacoustic and electroencephalographic signals in an acute seizure model of epilepsy. Our results demonstrate that both the neural and vascular responses during seizures in freely moving rats have characteristics which are observed to be different and more diverse from that of anesthetized rats. This implies that the neurovascular coupling in seizure in free moving animals are more complicated, which calls for more detailed study in future. To the best of our knowledge, this is the first time for hemodynamic monitoring of seizure in free moving animals. This technology also promises for other hemodynamic related research study in freely moving small animals. PMID:25450312

  15. Phase shift in the 24-hour rhythm of hippocampal EEG spiking activity in a rat model of temporal lobe epilepsy

    PubMed Central

    Stanley, David A.; Talathi, Sachin S.; Parekh, Mansi B.; Cordiner, Daniel J.; Zhou, Junli; Mareci, Thomas H.; Ditto, William L.

    2013-01-01

    For over a century epileptic seizures have been known to cluster at specific times of the day. Recent studies have suggested that the circadian regulatory system may become permanently altered in epilepsy, but little is known about how this affects neural activity and the daily pattern of seizures. To investigate, we tracked long-term changes in the rate of spontaneous hippocampal EEG spikes (SPKs) in a rat model of temporal lobe epilepsy. In healthy animals, SPKs oscillated with near 24-h period; however, after injury by status epilepticus, a persistent phase shift of ∼12 h emerged in animals that later went on to develop chronic spontaneous seizures. Additional measurements showed that global 24-h rhythms, including core body temperature and theta state transitions, did not phase shift. Instead, we hypothesized that locally impaired circadian input to the hippocampus might be responsible for the SPK phase shift. This was investigated with a biophysical computer model in which we showed that subtle changes in the relative strengths of circadian input could produce a phase shift in hippocampal neural activity. MRI provided evidence that the medial septum, a putative circadian relay center for the hippocampus, exhibits signs of damage and therefore could contribute to local circadian impairment. Our results suggest that balanced circadian input is critical to maintaining natural circadian phase in the hippocampus and that damage to circadian relay centers, such as the medial septum, may disrupt this balance. We conclude by discussing how abnormal circadian regulation may contribute to the daily rhythms of epileptic seizures and related cognitive dysfunction. PMID:23678009

  16. More Docked Vesicles and Larger Active Zones at Basket Cell-to-Granule Cell Synapses in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Yamawaki, Ruth; Thind, Khushdev

    2016-01-01

    Temporal lobe epilepsy is a common and challenging clinical problem, and its pathophysiological mechanisms remain unclear. One possibility is insufficient inhibition in the hippocampal formation where seizures tend to initiate. Normally, hippocampal basket cells provide strong and reliable synaptic inhibition at principal cell somata. In a rat model of temporal lobe epilepsy, basket cell-to-granule cell (BC→GC) synaptic transmission is more likely to fail, but the underlying cause is unknown. At some synapses, probability of release correlates with bouton size, active zone area, and number of docked vesicles. The present study tested the hypothesis that impaired GABAergic transmission at BC→GC synapses is attributable to ultrastructural changes. Boutons making axosomatic symmetric synapses in the granule cell layer were reconstructed from serial electron micrographs. BC→GC boutons were predicted to be smaller in volume, have fewer and smaller active zones, and contain fewer vesicles, including fewer docked vesicles. Results revealed the opposite. Compared with controls, epileptic pilocarpine-treated rats displayed boutons with over twice the average volume, active zone area, total vesicles, and docked vesicles and with more vesicles closer to active zones. Larger active zones in epileptic rats are consistent with previous reports of larger amplitude miniature IPSCs and larger BC→GC quantal size. Results of this study indicate that transmission failures at BC→GC synapses in epileptic pilocarpine-treated rats are not attributable to smaller boutons or fewer docked vesicles. Instead, processes following vesicle docking, including priming, Ca2+ entry, or Ca2+ coupling with exocytosis, might be responsible. SIGNIFICANCE STATEMENT One in 26 people develops epilepsy, and temporal lobe epilepsy is a common form. Up to one-third of patients are resistant to currently available treatments. This study tested a potential underlying mechanism for previously reported

  17. The inhibition of transforming growth factor beta-activated kinase 1 contributed to neuroprotection via inflammatory reaction in pilocarpine-induced rats with epilepsy.

    PubMed

    Tian, Q; Xiao, Q; Yu, W; Gu, M; Zhao, N; Lü, Y

    2016-06-14

    Recently, more and more studies support that inflammation is involved in the pathogenesis of epilepsy. Although TGFβ signaling is involved in epileptogenesis, whether TGFβ-associated neuroinflammation is sufficient to regulate epilepsy remains unknown to date. Furthermore, tumor necrosis factor-α receptor-associated factor-6 (TRAF6), transforming growth factor beta-activated kinase 1 (TAK1), which are the key elements of TGFβ-associated inflammation, is still unclear in epilepsy. Therefore, the present study aimed to explore the role of TRAF6 and TAK1 in pilocarpine-induced epileptic rat model. Firstly, the gene levels and protein expression of TRAF6 and TAK1 were detected in different time points after pilocarpine-induced status epilepticus (SE). 5z-7-oxozeaenol treatment (TAK1 antagonist) was then performed; the changes in TRAF6, TAK1, phosphorylated-TAK1 (P-TAK1), interleukin-1β (IL-1β) levels, neuronal survival and apoptosis, and seizure activity were detected. Our results showed that expressions of TRAF6 were increased after SE, reached the peak in 7day, maintained at the high level to 30days, and the TAK1, P-TAK1 levels were increased after SE following time. After 5z-7-oxozeaenol treatment in epileptic rats, TRAF6-TAK1-P-TAK1 signaling protein expressions were reduced, inflammatory cytokine IL-1β expression was decreased, neuron survival index was improved, the neuron apoptosis index was decreased and seizure durations were alleviated. In conclusion, the expression of TRAF6 and TAK1 are related to the progression of epilepsy. TAK1 might be a potential intervention target for the treatment of epilepsy via neuroprotection. PMID:27012613

  18. Decreased norepinephrine (NE) uptake in cerebral cortex and inferior colliculus of genetically epilepsy prone (GEP) rats

    SciTech Connect

    Browning, R.A.; Rigler-Daugherty, S.K.; Long, G.; Jobe, P.C.; Wade, D.R.

    1986-03-01

    GEP rats are characterized by an enhanced susceptibility to seizures caused by a variety of stimuli, most notably sound. Pharmacological treatments that reduce the synaptic concentration of NE increase seizure severity in GEP rats while elevations in NE have the opposite effect. GEP rats also display a widespread deficit in brain NE concentration suggesting that their increased seizure susceptibility is related to a deficit in noradrenergic transmission. The authors have compared the kinetics of /sup 3/H-NE uptake in the P/sub 2/ synaptosomal fraction isolated from the cerebral cortex of normal and GEP-rats. Although the apparent Kms were not significantly different (Normal +/- SEM:0.37 +/- 0.13..mu..M; GEP +/- SEM: 0.29 +/- 0.07..mu..M), the Vmax for GEP rats was 48% lower than that of normal rats (Normal +/- SEM: 474 +/- 45 fmole/mg/4min; GEP +/- SEM: 248 +/- 16 fmole/mg/4min). Because of the possible role of the inferior colliculus (IC) in the initiation of sound-induced seizures in GEP rats, the authors measured synaptosomal NE uptake in the IC using a NE concentration of 50 nM. The IC synaptosomal NE uptake was found to be 35% lower in GEP than in normal rats. These findings are consistent with the hypothesis that a deficit in noradrenergic transmission is related to the increased seizure susceptibility of GEP rats.

  19. Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

    PubMed Central

    Alsharafi, Walid A.; Xiao, Bo; Abuhamed, Mutasem M.; Bi, Fang-Fang; Luo, Zhao-Hui

    2015-01-01

    Accumulating evidence is emerging that microRNAs (miRNAs) are key regulators in controlling neuroinflammatory responses that are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE). The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL)-10 as an anti-inflammatory cytokine and miR-187 as a post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE) and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus 2 h, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS) and IL-10-stimulated neurons were performed. Furthermore, we identified the effect of antagonizing miR-187 by its antagomir on IL-10 secretion. Here, we reported that IL-10 secretion and miR-187 expression levels are inversely correlated after SE. In patients with TLE, the expression of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10–dependent manner. On the other hand, antagonizing miR-187 promoted the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE. PMID:26696826

  20. Plic-1, a new target in repressing epileptic seizure by regulation of GABAAR function in patients and a rat model of epilepsy.

    PubMed

    Zhang, Yujiao; Li, Zengyou; Gu, Juan; Zhang, Yanke; Wang, Wei; Shen, Hui; Chen, Guojun; Wang, Xuefeng

    2015-12-01

    Dysfunction of γ-aminobutyric acid A (GABAA) receptors (GABAARs) is a prominent factor affecting intractable epilepsy. Plic-1, an ubiquitin-like protein enriched in the inhibitory synapses connecting GABAARs and the ubiquitin protease system (UPS), plays a key role in the modification of GABAAR functions. However, the relationship between Plic-1 and epileptogenesis is not known. In the present study, we aimed to investigate Plic-1 levels in patients with temporal lobe epilepsy, as well as the role of Plic-1 in regulating onset and progression of epilepsy in animal models. We found that Plic-1 expression was significantly decreased in patients with epilepsy as well as pilocarpine- and pentylenetetrazol (PTZ)-induced rat epileptic models. Intrahippocampal injection of the PePα peptide, which disrupts Plic-1 binding to GABAARs, significantly shortened the latency of seizure onset, and increased the seizure severity and duration in these two epileptic models. Overexpressed Plic-1 through lentivirus transfection into a PTZ model resulted in a reduction in both seizure severity and generalized tonic-clonic seizure duration. Whole-cell clamp recordings revealed that the PePα peptide decreased miniature inhibitory postsynaptic currents (mIPSCs) whereas overexpressed Plic-1 increased mIPSCs in the pyramidal neurons of the hippocampus. These effects can be blocked by picrotoxin, a GABAAR inhibitor. Our results indicate that Plic-1 plays an important role in managing epileptic seizures by enhancing seizure inhibition through regulation of GABAARs at synaptic sites. PMID:26415648

  1. Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight

    NASA Technical Reports Server (NTRS)

    Jiang, Bian; Roy, Roland R.; Navarro, Christine; Edgerton, V. R.

    1993-01-01

    The effect of a 4-day-long spaceflight on the size and the enzyme properties of soleus fibers of rats and the effects of exogenous growth hormone (GH) on the atrophic response of the soleus muscle were investigated in four groups of rats: (1) control, (2) control plus GH treatment, (3) flight, and (4) flight plus GH treatment. Results showed that the fiber size and the type of myosin heavy chain expressed fibers (but not the metabolic properties) of the soleus were affected by four days of weightlessness and that the effects were not ameliorated by the administration of growth hormone.

  2. Reproduction and progeny growth in rats fed clinoptilolite in the presence or absence of dietary cadmium

    SciTech Connect

    Pond, W.G.; Yen, J.T.

    1983-12-01

    The purposes of the experiment reported were to determine the effects of long-term ingestion of clinoptilolite on reproduction in female rats and on the postnatal development of their progeny and to ascertain whether or not clinoptilolite offers protection against the toxic effects of long-term Cd ingestion.

  3. EFFECTS OF 5-FLUOROURACIL ON EMBRYONIC RAT PALATE IN VITRO: FUSION IN THE ABSENCE OF PROLIFERATION

    EPA Science Inventory

    5-Fluorouracil (5-FU) inhibits the enzyme thymidylate synthetase (TS) which results in inhibition of DNA synthesis. 5-FU is teratogenic in many species, inducing cleft palate, limb, and tail defects. n the present study, GD 14 embryonic rat palates were exposed to 5-FU in organ c...

  4. Epilepsy Foundation

    MedlinePlus

    ... Community Conference 2015 Epilepsy Pipeline Community Conference Purple Pumpkin Project Hidden Truths, The Mind Unraveled Downtown Downstairs ... Community Conference 2015 Epilepsy Pipeline Community Conference Purple Pumpkin Project Hidden Truths, The Mind Unraveled Downtown Downstairs ...

  5. Epilepsy - overview

    MedlinePlus

    Epilepsy is a brain disorder in which a person has repeated seizures over time. Seizures are episodes ... Epilepsy occurs when permanent changes in the brain cause it to be too excitable or irritable. As ...

  6. Comparative power spectrum analysis of EEG activity in spontaneously hypertensive and Wistar rats in kainate model of temporal model of epilepsy.

    PubMed

    Tchekalarova, Jana; Kortenska, Lidia; Marinov, Pencho; Boyanov, Kiril

    2016-06-01

    Recently, we have reported that spontaneously hypertensive rats (SHRs) exhibit higher susceptibility than Wistar rats in kainate (KA) model of epilepsy. The aim of the present study is to compare the baseline of EEG signals in SHRs and Wistar rats using Discrete Fourier transform (DFT) during the three phases of KA model (acute, latent and chronic). The SHRs showed higher baseline relative power of delta waves in the left frontal cortex and lower gamma-HF waves in the left frontal and left/right parietal cortex, respectively, compared to Wistar rats. During the acute phase, both absolute and relative power of fast EEG bands (gamma-HF) was lower in the left/right frontal and the left/right parietal cortex in SHRs compared to Wistar rats. During the latent phase, no difference in the power of the investigated bands was detected between the two strains. During the chronic epileptic phase, the SHRs were characterized with higher power of HF oscillations than Wistar rats both in the frontal and parietal cortex without brain lateralization while theta, alpha and beta bands were with diminished power in the left parietal cortex of SHRs compared to normotensive Wistar rats. Taken together, the presented results suggest that the increased delta waves and lower gamma-HF waves in the frontal/parietal cortex are associated with a higher seizure susceptibility of SHRs compared to Wistar rats while fastest oscillations has a critical role in seizure generation and propagation of hypertensive rats. PMID:27040713

  7. Functional glycine receptor maturation in the absence of glycinergic input in dopaminergic neurones of the rat substantia nigra

    PubMed Central

    Mangin, J M; Guyon, A; Eugène, D; Paupardin-Tritsch, D; Legendre, P

    2002-01-01

    The postnatal maturation pattern of glycine receptor channels (GlyRs) expressed by dopaminergic (DA) neurones of the rat substantia nigra pars compacta (SNc) was investigated using single-channel and whole-cell patch-clamp recordings in brain slices from rats aged 7–21 postnatal days (P). In neonatal rats (P7-P10), GlyRs exhibited a main conductance state of 100–110 pS with a mean open time of 16 ms. In juvenile rats (P19-P22), both the GlyR main conductance state (46-55 pS) and the mean open time (6.8 ms) were decreased. In neonatal rats, application of 30 μm picrotoxin, which is known to block homomeric GlyRs, strongly reduced glycine-evoked responses, while it was much less effective in juvenile rats. These results suggest that these GlyRs correspond functionally to α2 homomeric GlyRs in neonatal rats and α1/β heteromeric GlyRs in juvenile rats. A drastic but transient decrease in the glycine responsiveness of DA neurones occurred around P17 concomitant to the functional switch from the homomeric state to the heteromeric state. This age corresponds to a maturation phase for DA neurones. The application of 1 μm gabazine blocked spontaneous or evoked inhibitory synaptic current, while the addition of 1 μm strychnine had no effect, suggesting a lack of functional glycinergic synapses on DA neurones. Although it has been proposed that taurine is co-released with GABA at GABAergic synapses on DA neurones, in the present study the stimulation of GABAergic fibres failed to activate GlyRs. Blockade of taurine transporters and applications of high K+ and hyposmotic solutions were also unable to induce any strychnine-sensitive current. We conclude that functional maturation of GlyRs can occur in the absence of any detectable GlyR activation in DA neurones of the SNc. PMID:12154171

  8. Kainic acid-induced F-344 rat model of mesial temporal lobe epilepsy: gene expression and canonical pathways.

    PubMed

    Sharma, Alok K; Searfoss, George H; Reams, Rachel Y; Jordan, William H; Snyder, Paul W; Chiang, Alan Y; Jolly, Robert A; Ryan, Timothy P

    2009-10-01

    Mesial temporal lobe epilepsy (MTLE) is a severe neurological condition of unknown pathogenesis for which several animal models have been developed. To obtain a better understanding of the underlying molecular mechanisms and identify potential biomarkers of lesion progression, we used a rat kainic acid (KA) treatment model of MTLE coupled with global gene expression analysis to examine temporal (four hours, days 3, 14, or 28) gene regulation relative to hippocampal histopathological changes. The authors recommend reviewing the companion histopathology paper (Sharma et al. 2008) to get a better understanding of the work presented here. Analysis of filtered gene expression data using Ingenuity Pathways Analysis (Ingenuity Systems, http://www.ingenuity.com) revealed that a number of genes pertaining to neuronal plasticity (RhoA, Rac1, Cdc42, BDNF, and Trk), neurodegeneration (Caspase3, Calpain 1, Bax, a Cytochrome c, and Smac/Diablo), and inflammation/immune-response pathways (TNF-alpha, CCL2, Cox2) were modulated in a temporal fashion after KA treatment. Expression changes for selected genes known to have a role in neuronal plasticity were subsequently validated by quantitative polymerase chain reaction (qPCR). Notably, canonical pathway analysis revealed that a number of genes within the axon guidance signaling canonical pathway were up-regulated from Days 3 to 28, which correlated with aberrant mossy fiber (MF) sprouting observed histologically beginning at Day 6. Importantly, analysis of the gene expression data also identified potential biomarkers for monitoring neurodegeneration (Cox2) and neuronal/synaptic plasticity (Kalrn). PMID:19700661

  9. Mapping parahippocampal systems for recognition and recency memory in the absence of the rat hippocampus

    PubMed Central

    Kinnavane, L; Amin, E; Horne, M; Aggleton, J P

    2014-01-01

    The present study examined immediate-early gene expression in the perirhinal cortex of rats with hippocampal lesions. The goal was to test those models of recognition memory which assume that the perirhinal cortex can function independently of the hippocampus. The c-fos gene was targeted, as its expression in the perirhinal cortex is strongly associated with recognition memory. Four groups of rats were examined. Rats with hippocampal lesions and their surgical controls were given either a recognition memory task (novel vs. familiar objects) or a relative recency task (objects with differing degrees of familiarity). Perirhinal Fos expression in the hippocampal-lesioned groups correlated with both recognition and recency performance. The hippocampal lesions, however, had no apparent effect on overall levels of perirhinal or entorhinal cortex c-fos expression in response to novel objects, with only restricted effects being seen in the recency condition. Network analyses showed that whereas the patterns of parahippocampal interactions were differentially affected by novel or familiar objects, these correlated networks were not altered by hippocampal lesions. Additional analyses in control rats revealed two modes of correlated medial temporal activation. Novel stimuli recruited the pathway from the lateral entorhinal cortex (cortical layer II or III) to hippocampal field CA3, and thence to CA1. Familiar stimuli recruited the direct pathway from the lateral entorhinal cortex (principally layer III) to CA1. The present findings not only reveal the independence from the hippocampus of some perirhinal systems associated with recognition memory, but also show how novel stimuli engage hippocampal subfields in qualitatively different ways from familiar stimuli. PMID:25264133

  10. Seizure severity and duration in the cortical stimulation model of experimental epilepsy in rats: a longitudinal study.

    PubMed

    Nelson, Timothy S; Suhr, Courtney L; Lai, Alan; Halliday, Amy J; Freestone, Dean R; McLean, Karen J; Burkitt, Anthony N; Cook, Mark J

    2010-05-01

    The aim of this study was to determine the current intensities necessary to elicit three levels of varying EEG and behavioural phenomena with electrical stimulation, and also to determine the consistency of the EEG and behavioural components of the triggered seizures over time. Electrical stimulation of the primary motor/somatosensory cortex was performed in 16 adult rats with multichannel microwire electrode arrays. Stimulation was delivered at a frequency of 60 Hz (1 ms pulse width), for 2 s duration, as biphasic rectangular pulses over four of the eight available electrode pairs. Current intensity thresholds for interruption of normal behaviour, epileptiform afterdischarge (EAD) longer than 5 s and motor seizures with Racine severity greater than 3 were not correlated to time post-surgery. The Racine threshold was shown to be negatively correlated to the EAD duration and Racine severity of seizures elicited in the following sessions. Seizures were reliably generated in rats through cortical stimulation with microwire electrode arrays and these seizures were not shown to be subject to any kindling type effects up to 53 days post-implantation. Both the electrographic duration and behavioural severity of stimulated seizures remained, on average, constant during this experimental period. Approximately one-third of stimulations did not cause observable motor seizures and of those that did result in seizures, forelimb clonus was the most common manifestation and the mean EAD duration was 18.5 s. No damage beyond that caused by surgical implantation of electrodes was observed in the histological analyses of stimulated and non-stimulated tissue. The consistency, duration and severity of seizures within this timeframe make this cortical stimulation model suitable for investigations into novel therapeutic interventions for epilepsy that require a known seizure focus. PMID:20153951

  11. Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy.

    PubMed

    Gruenbaum, Shaun E; Wang, Helen; Zaveri, Hitten P; Tang, Amber B; Lee, Tih-Shih W; Eid, Tore; Dhaher, Roni

    2015-10-01

    The prevalence of depression and suicide is increased in patients with mesial temporal lobe epilepsy (MTLE); however, the underlying mechanism remains unknown. Anhedonia, a core symptom of depression that is predictive of suicide, is common in patients with MTLE. Glutamine synthetase, an astrocytic enzyme that metabolizes glutamate and ammonia to glutamine, is reduced in the amygdala in patients with epilepsy and depression and in suicide victims. Here, we sought to develop a novel model of anhedonia in MTLE by testing the hypothesis that deficiency in glutamine synthetase in the central nucleus of the amygdala (CeA) leads to epilepsy and comorbid anhedonia. Nineteen male Sprague-Dawley rats were implanted with an osmotic pump infusing either the glutamine synthetase inhibitor methionine sulfoximine [MSO (n=12)] or phosphate buffered saline [PBS (n=7)] into the right CeA. Seizure activity was monitored by video-intracranial electroencephalogram (EEG) recordings for 21days after the onset of MSO infusion. Sucrose preference, a measure of anhedonia, was assessed after 21days. Methionine sulfoximine-infused rats exhibited recurrent seizures during the monitoring period and showed decreased sucrose preference over days when compared with PBS-infused rats (p<0.01). Water consumption did not differ between the PBS-treated group and the MSO-treated group. Neurons were lost in the CeA, but not the medial amygdala, lateral amygdala, basolateral amygdala, or the hilus of the dentate gyrus, in the MSO-treated rats. The results suggest that decreased glutamine synthetase activity in the CeA is a possible common cause of anhedonia and seizures in TLE. We propose that the MSO CeA model can be used for mechanistic studies that will lead to the development and testing of novel drugs to prevent seizures, depression, and suicide in patients with TLE. PMID:26262937

  12. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

    PubMed Central

    Gao, Fei; Gao, Ying; Liu, Yang-feng; Wang, Li; Li, Ya-jun

    2014-01-01

    Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE), malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden. PMID:25419137

  13. Absence of organ specific toxicity in rats treated with Tonica, an aqueous herbal haematinic preparation.

    PubMed

    Martey, Orleans Nii-Korley; Armah, George; Okine, Laud K N-A

    2010-01-01

    The sub-chronic toxicity of Tonica, an aqueous herbal haematinic prepared from the stem barks of Khaya senegalensis, Mitragyna stipulosa and Kigelia africana, was investigated in male Sprague-Dawley rats at 28, 280 and 560 mg kg(-1) day(-1), representing the normal human dose, 10x and 20x that dose, respectively for 6 weeks. The growth rate of animals over the period of treatment and certain serum biochemical and haematological indices as well as urinalysis and weight of selected organs at termination, were determined. Results show that the extract did not affect the weight gain of the animals with time or the mean wet weights of selected organs. Although there were slight but insignificant (p>0.05) elevations in WBC (16-27%) and PLT (8-11%) counts in Tonica-treated animals compared to controls at 10x and 20x the normal dose, most serum biochemical, haematological and urinalysis data indicated no significant differences (p>0.05) between tests and control rats. There were also no changes in the morphology of liver, kidney, lung and heart tissues as a result of Tonica treatment. These findings suggest that Tonica is safe at the dosage regimens administered to the animals in this study, and there appears to be no overt organ specific toxicity associated with it. PMID:21461151

  14. Persistent Hyperactivity of Hippocampal Dentate Interneurons After a Silent Period in the Rat Pilocarpine Model of Epilepsy

    PubMed Central

    Wang, Xiaochen; Song, Xinyu; Wu, Lin; Nadler, J. Victor; Zhan, Ren-Zhi

    2016-01-01

    Profile of GABAergic interneuron activity after pilocarpine-induced status epilepticus (SE) was examined in the rat hippocampal dentate gyrus by analyzing immediate early gene expression and recording spontaneous firing at near resting membrane potential (REM). SE for exact 2 h or more than 2 h was induced in the male Sprague-Dawley rats by an intraperitoneal injection of pilocarpine. Expression of immediate early genes (IEGs) was examined at 1 h, 1 week, 2 weeks or more than 10 weeks after SE. For animals to be examined at 1 h after SE, SE lasted for exact 2 h was terminated by an intraperitoneal injection of diazepam. Spontaneous firing at near the REM was recorded in interneurons located along the border between the granule cell layer and the hilus more than 10 weeks after SE. Results showed that both c-fos and activity-regulated cytoskeleton associated protein (Arc) in hilar GABAergic interneurons were up-regulated after SE in a biphasic manner; they were increased at 1 h and more than 2 weeks, but not at 1 week after SE. Ten weeks after SE, nearly 60% of hilar GABAergic cells expressed c-fos. With the exception of calretinin (CR)-positive cells, percentages of hilar neuronal nitric oxide synthase (nNOS)-, neuropeptide Y (NPY)-, parvalbumin (PV)-, and somatostatin (SOM)-positive cells with c-fos expression are significantly higher than those of controls more than 10 weeks after SE. Without the REM to be more depolarizing and changed threshold potential level in SE-induced rats, cell-attached recording revealed that nearly 90% of hilar interneurons fired spontaneously at near the REM while only 22% of the same cell population did so in the controls. In conclusion, pilocarpine-induced SE eventually leads to a state in which surviving dentate GABAergic interneurons become hyperactive with a subtype-dependent manner; this implies that a fragile balance between excitation and inhibition exists in the dentate gyrus and in addition, the activity-dependent up

  15. Absence of transsynaptic transport in cerebello-thalamo-cortical path of the rat.

    PubMed

    Petrovic-Minic, B; Mojsilovic-Petrovic, J; Holm, S; Mogensen, J; Divac, I

    1994-01-01

    Attempts to visualize the cerebello-thalamo-cortical path in the rat were made with different approaches. We tried (1) double labelling with somatopetal tracing from the motor cortex and somatofugal from the cerebellar nuclei, (2) transmembrane labelling by depositing biocytin or wheat germ agglutinin (WGA) into the motor cortex or cerebellum. WGA was either iodinated with 125I or conjugated with horseradish peroxidase (HRP). The double labelling technique showed an overlap of the tracers in the same thalamic region but no evidence of transsynaptic transport in either direction was obtained. Our results indicate a difference in the organization of this system in primates and rodents, since transsynaptic labelling in the cerebellar nuclei after injections of WGA-HRP conjugate in the monkey motor cortex has been found. PMID:7517613

  16. Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats.

    PubMed

    Holson, J F; Stump, D G; Ulrich, C E; Farr, C H

    1999-09-01

    A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guidelines and with exposure throughout gestation. In the present study, inorganic arsenic, as arsenic trioxide (As(+3), As2O3), was administered via whole-body inhalational exposure to groups of twenty-five Crl:CD(SD)BR female rats for six h per day every day, beginning fourteen days prior to mating and continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As(+3) in the dams prior to embryonal-fetal development. In a preliminary exposure range-finding study, half of the females that had been exposed to arsenic trioxide at 25 mg/m3 died or were euthanized in extremis. In the definitive study, target exposure levels were 0.3, 3.0, and 10.0 mg/m3. Maternal toxicity, which was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational exposure, was observed only at the 10 mg/m3 exposure level. Intrauterine parameters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No treatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m3; the NOAEL for developmental toxicity was greater than or equal to 10 mg/m3, 760 times both the time-weighted average threshold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, when administered via whole-body inhalation to pregnant rats, is not a developmental toxicant. PMID:10496680

  17. GABRB3 mutation, G32R, associated with childhood absence epilepsy alters α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor expression and channel gating.

    PubMed

    Gurba, Katharine N; Hernandez, Ciria C; Hu, Ningning; Macdonald, Robert L

    2012-04-01

    A GABA(A) receptor β3 subunit mutation, G32R, has been associated with childhood absence epilepsy. We evaluated the possibility that this mutation, which is located adjacent to the most N-terminal of three β3 subunit N-glycosylation sites, might reduce GABAergic inhibition by increasing glycosylation of β3 subunits. The mutation had three major effects on GABA(A) receptors. First, coexpression of β3(G32R) subunits with α1 or α3 and γ2L subunits in HEK293T cells reduced surface expression of γ2L subunits and increased surface expression of β3 subunits, suggesting a partial shift from ternary αβ3γ2L receptors to binary αβ3 and homomeric β3 receptors. Second, β3(G32R) subunits were more likely than β3 subunits to be N-glycosylated at Asn-33, but increases in glycosylation were not responsible for changes in subunit surface expression. Rather, both phenomena could be attributed to the presence of a basic residue at position 32. Finally, α1β3(G32R)γ2L receptors had significantly reduced macroscopic current density. This reduction could not be explained fully by changes in subunit expression levels (because γ2L levels decreased only slightly) or glycosylation (because reduction persisted in the absence of glycosylation at Asn-33). Single channel recording revealed that α1β3(G32R)γ2L receptors had impaired gating with shorter mean open time. Homology modeling indicated that the mutation altered salt bridges at subunit interfaces, including regions important for subunit oligomerization. Our results suggest both a mechanism for mutation-induced hyperexcitability and a novel role for the β3 subunit N-terminal α-helix in receptor assembly and gating. PMID:22303015

  18. Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy.

    PubMed

    Fang, Ziyan; Chen, Shuda; Qin, Jiaming; Chen, Bao; Ni, Guanzhong; Chen, Ziyi; Zhou, Jueqian; Li, Ze; Ning, Yuping; Wu, Chuanbin; Zhou, Liemin

    2016-08-01

    P-glycoprotein (Pgp) overexpression in the blood brain barrier (BBB) is hypothesized to lower brain drug concentrations and thus inhibit anticonvulsant effects in drug-resistant epilepsy. Recently, the poly(butylcyanoacrylate) (PBCA) nanoparticle system was shown to overcome the obstacle of the BBB to deliver drugs into the brain. To determine whether pluronic P85-coated phenytoin poly(butylcyanoacrylate) nanoparticles (P85-PHT-PBCA-NPs) target PHT to the brain, PHT-resistant rats overexpressing Pgp in the BBB were screened by response to PHT treatment after chronic temporal lobe epilepsy induced by lithium-pilocarpine, followed by direct verification of PHT transport via measurement of brain PHT concentrations using microdialysis. Thereafter, the PHT-resistant rats were divided into three groups, which were treated with PHT, PHT + tariquidar (TQD), or P85-PHT-PBCA-NPs. PHT + TQD and P85-PHT-PBCA-NPs showed anticonvulsant activity in the PHT-resistant rats and increased the ratio of the area under the curve of the PHT concentrations in the brain/plasma in comparison with that observed in animals subjected to PHT treatment. However, the ratios of the PHT concentrations in the liver/plasma and kidney/plasma following P85-PHT-PBCA-NPs treatment were much lower than those measured following PHT + TQD treatment. Thus, Pgp overexpression decreases therapeutic drug concentrations in the brains of subjects with drug-resistant epilepsy and P85-PHT-PBCA-NPs could increase these drug concentrations. PMID:27162079

  19. Photosensitive epilepsy in children.

    PubMed

    Aso, K; Watanabe, K; Negoro, T; Haga, Y; Kito, M; Maeda, N; Ohki, T

    1994-03-01

    We performed a retrospective analysis of 17 children with photosensitive seizures (PSS) who had been followed for more than 3 years (mean: 9 years). PSS were verified in all patients by simultaneous video-EEG monitoring. The seizures were precipitated by flickering stroboscopes (14 patients) or were induced by patients themselves (3) with head-nodding in front of illumination, blinking at television or close viewing of striped patterns. PSS consisted of myoclonic seizures (eight patients), generalized tonic-clonic convulsions (5), partial seizures (3) or atypical absence (1). According to the International Classification of Epileptic Syndrome, three patients were classified as having severe myoclonic epilepsy in infancy and five as having juvenile myoclonic epilepsy. The remaining nine could not be categorized as any specific epileptic syndrome. Children with age of the onset of epilepsy at 7 years or younger tended to suffer intellectual deficit in addition to intractable seizures. PMID:8044456

  20. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

    PubMed Central

    2011-01-01

    Background Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE) release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ) rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function. Methods Cardiac sympathetic nervous integrity was investigated in vivo via biodistribution of the positron emission tomography radiotracer and NE analogue [11C]meta-hydroxyephedrine ([11C]HED). Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET) expression were evaluated as correlative measurements. Results The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [11C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle. Conclusions Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system signaling in the absence of

  1. Variations in elemental compositions of rat hippocampal formation between acute and latent phases of pilocarpine-induced epilepsy: an X-ray fluorescence microscopy study.

    PubMed

    Chwiej, J; Dulinska, J; Janeczko, K; Appel, K; Setkowicz, Z

    2012-06-01

    There is growing experimental evidence that tracing the elements involved in brain hyperexcitability, excitotoxicity, and/or subsequent neurodegeneration could be a valuable source of data on the molecular mechanisms triggering or promoting further development of epilepsy. The most frequently used experimental model of the temporal lobe epilepsy observed in clinical practice is the one based on pilocarpine-induced seizures. In the frame of this study, the elemental anomalies occurring for the rat hippocampal tissue in acute and silent periods after injection of pilocarpine in rats were compared. X-ray fluorescence microscopy was applied for the topographic and quantitative elemental analysis. The differences in the levels of elements such as P, S, K, Ca, Fe, Cu, and Zn between the rats 3 days (SE72) and 6 h (SE6) after pilocarpine injection as well as naive controls were examined. Comparison of SE72 and control groups showed, for specific areas of the hippocampal formation, lower levels of P, K, Cu, and Zn, and an increase in Ca accumulation. These results as well as further analysis of the differences between the SE72 and SE6 groups confirmed that seizure-induced excitotoxicity as well as mossy fiber sprouting are the mechanisms involved in the neurodegenerative processes which may finally lead to spontaneous seizures in the chronic period of the pilocarpine model. Moreover, in the light of the results obtained, Cu seems to play a very important role in the pathogenesis of epilepsy in this animal model. For all areas analyzed, the levels of this element recorded in the latent period were not only lower than those for controls but were even lower than the levels found in the acute period. The decreased hippocampal accumulation of Cu in the phase of behavior and EEG stabilization, a possible inhibitory effect of this element on excitatory amino acid receptors, and enhanced seizure susceptibility in Menkes disease (an inherited Cu transport disorder leading to Cu

  2. Musicogenic epilepsy.

    PubMed

    Stern, John

    2015-01-01

    Musicogenic epilepsy, which is a form of reflex epilepsy, is characterized by the triggering of epileptic seizures by specific music experiences. Individuals with musicogenic epilepsy differ in the music trigger, but may have similar seizures. Typically, these seizures are focal dyscognitive and have a temporal-lobe origin with a limbic system distribution. As such, the music trigger is likely related to either an emotional or memory aspect of music perception. Investigations into musicogenic epilepsy may lead to a better understanding of seizure propagation within the brain and of neurologic aspects of the music experience. Successful treatment of medication-resistant musicogenic epilepsy has been achieved with anterior temporal-lobe resection. PMID:25726285

  3. Cellular and network mechanisms of genetically-determined absence seizures.

    PubMed

    Pinault, Didier; O'Brien, Terence J

    2005-01-01

    The absence epilepsies are characterized by recurrent episodes of loss of consciousness associated with generalized spike-and-wave discharges, with an abrupt onset and offset, in the thalamocortical system. In the absence of detailed neurophysiological studies in humans, many of the concepts regarding the pathophysiological basis of absence seizures are based on studies in animal models. Each of these models has its particular strengths and limitations, and the validity of findings from these models for the human condition cannot be assumed. Consequently, studies in different models have produced some conflicting findings and conclusions. A long-standing concept, based primarily from studies in vivo in cats and in vitro brain slices, is that these paroxysmal electrical events develop suddenly from sleep-related spindle oscillations. More specifically, it is proposed that the initial mechanisms that underlie absence-related spike-and-wave discharges are located in the thalamus, involving especially the thalamic reticular nucleus. By contrast, more recent studies in well-established, genetic models of absence epilepsy in rats demonstrate that spike-and-wave discharges originate in a cortical focus and develop from a wake-related natural corticothalamic sensorimotor rhythm. In this review we integrate recent findings showing that, in both the thalamus and the neocortex, genetically-determined, absence-related spike-and-wave discharges are the manifestation of hypersynchronized, cellular, rhythmic excitations and inhibitions that result from a combination of complex, intrinsic, synaptic mechanisms. Arguments are put forward supporting the hypothesis that layer VI corticothalamic neurons act as 'drivers' in the generation of spike-and-wave discharges in the somatosensory thalamocortical system that result in corticothalamic resonances particularly initially involving the thalamic reticular nucleus. However an important unresolved question is: what are the cellular and

  4. MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy – comparison with human epileptic samples

    PubMed Central

    Roncon, Paolo; Soukupovà, Marie; Binaschi, Anna; Falcicchia, Chiara; Zucchini, Silvia; Ferracin, Manuela; Langley, Sarah R.; Petretto, Enrico; Johnson, Michael R.; Marucci, Gianluca; Michelucci, Roberto; Rubboli, Guido; Simonato, Michele

    2015-01-01

    The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR-181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis. PMID:26382856

  5. MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy--comparison with human epileptic samples.

    PubMed

    Roncon, Paolo; Soukupovà, Marie; Binaschi, Anna; Falcicchia, Chiara; Zucchini, Silvia; Ferracin, Manuela; Langley, Sarah R; Petretto, Enrico; Johnson, Michael R; Marucci, Gianluca; Michelucci, Roberto; Rubboli, Guido; Simonato, Michele

    2015-01-01

    The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR-181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis. PMID:26382856

  6. Musicogenic epilepsy.

    PubMed

    Berman, I W

    1981-01-10

    Musicogenic epilepsy is a form of temporal lobe epilepsy, and belongs to the group of reflex epilepsies. Convulsions are generally triggered by a specific passage of music. It is not as rare as is generally assumed, and physicians and neurologists were aware of the condition as early as the latter part of the 19th century. Many of its sufferers have above-average musicality. In some patients autonomic manifestations are conspicuous, but their role as preciptation factors is not clear. Electro-encephalographic studies have shown conclusively that musicogenic epilepsy is not hysterical. Most but not all of its victims respond well to anti-ictal medication. Psychotherapy has a place in the treatment of some patients. PMID:7006106

  7. Epilepsy - overview

    MedlinePlus

    ... look at the brain and nervous system. An EEG (electroencephalogram) will be done to check the electrical ... epilepsy surgery, you may need to: Wear an EEG recorder for days or weeks as you go ...

  8. Epilepsy (partial)

    PubMed Central

    2011-01-01

    Introduction About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of starting antiepileptic drug treatment following a single seizure? What are the effects of drug monotherapy in people with partial epilepsy? What are the effects of additional drug treatments in people with drug-resistant partial epilepsy? What is the risk of relapse in people in remission when withdrawing antiepileptic drugs? What are the effects of behavioural and psychological treatments for people with epilepsy? What are the effects of surgery in people with drug-resistant temporal lobe epilepsy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or

  9. Increase in relative deposition of fine particles in the rat lung periphery in the absence of gravity

    PubMed Central

    Borja, Maria G.; Oakes, Jessica M.; Breen, Ellen C.; Olfert, I. Mark; Scadeng, Miriam; Prisk, G. Kim

    2014-01-01

    While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgravity (μG) compared with gravity on the ground (1G), the absence of sedimentation causes fine particles to penetrate deeper in the lung in μG. Using quantitative magnetic resonance imaging (MRI), we determined the effect of gravity on peripheral deposition (DEPperipheral) of fine particles. Aerosolized 0.95-μm-diameter ferric oxide particles were delivered to spontaneously breathing rats placed in plethysmographic chambers both in μG aboard the NASA Microgravity Research Aircraft and at 1G. Following exposure, lungs were perfusion fixed, fluid filled, and imaged in a 3T MR scanner. The MR signal decay rate, R2*, was measured in each voxel of the left lung from which particle deposition (DEP) was determined based on a calibration curve. Regional deposition was assessed by comparing DEP between the outer (DEPperipheral) and inner (DEPcentral) areas on each slice, and expressed as the central-to-peripheral ratio. Total lung deposition tended to be lower in μG compared with 1G (1.01 ± 0.52 vs. 1.43 ± 0.52 μg/ml, P = 0.1). In μG, DEPperipheral was larger than DEPcentral (P < 0.03), while, in 1G, DEPperipheral was not significantly different from DEPcentral. Finally, central-to-peripheral ratio was significantly less in μG than in 1G (P ≤ 0.05). These data show a larger fraction of fine particles depositing peripherally in μG than in 1G, likely beyond the large- and medium-sized airways. Although not measured, the difference in the spatial distribution of deposited particles between μG and 1G could also affect particle retention rates, with an increase in retention for particles deposited more peripherally. PMID:25170069

  10. 1400W, a highly selective inducible nitric oxide synthase inhibitor is a potential disease modifier in the rat kainate model of temporal lobe epilepsy.

    PubMed

    Puttachary, Sreekanth; Sharma, Shaunik; Verma, Saurabh; Yang, Yang; Putra, Marson; Thippeswamy, Achala; Luo, Diou; Thippeswamy, Thimmasettappa

    2016-09-01

    Status epilepticus (SE) initiates epileptogenesis to transform normal brain to epileptic state which is characterized by spontaneous recurrent seizures (SRS). Prior to SRS, progressive changes occur in the brain soon after SE, for example, loss of blood-brain barrier (BBB) integrity, neuronal hyper-excitability (epileptiform spiking), neuroinflammation [reactive gliosis, high levels of reactive oxygen/nitrogen species (ROS/RNS)], neurodegeneration and synaptic re-organization. Our hypothesis was that modification of early epileptogenic events will alter the course of disease development and its progression. We tested the hypothesis in the rat kainate model of chronic epilepsy using a novel disease modifying drug, 1400W, a highly selective inhibitor of inducible nitric oxide synthase (iNOS/NOS-II). In an in vitro mouse brain slice model, using a multi-electrode array system, co-application of 1400W with kainate significantly suppressed kainate-induced epileptiform spiking. In the rats, in vivo, 4h after the induction of SE with kainate, 1400W (20mg/kg, i.p.) was administered twice daily for three days to target early events of epileptogenesis. The rats were subjected to continuous (24/7) video-EEG monitoring, remotely, for six months from epidurally implanted cortical electrodes. The 1400W treatment significantly reduced the epileptiform spike rate during the first 12-74h post-SE, which resulted in >90% reduction in SRS in long-term during the six month period when compared to the vehicle-treated control group (257±113 versus 19±10 episodes). Immunohistochemistry (IHC) of brain sections at seven days and six months revealed a significant reduction in; reactive astrogliosis and microgliosis (M1 type), extravascular serum albumin (a marker for BBB leakage) and neurodegeneration in the hippocampus, amygdala and entorhinal cortex in the 1400W-treated rats when compared to the vehicle control. In the seven day group, hippocampal Western blots revealed downregulation of

  11. Expressions of tumor necrosis factor alpha and microRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy.

    PubMed

    Ashhab, Muhammad Usman; Omran, Ahmed; Kong, Huimin; Gan, Na; He, Fang; Peng, Jing; Yin, Fei

    2013-11-01

    Recently, the role of inflammation has attracted great attention in the pathogenesis of mesial temporal lobe epilepsy (MTLE), and microRNAs start to emerge as promising new players in MTLE pathogenesis. In this study, we investigated the dynamic expression patterns of tumor necrosis factor alpha (TNF-α) and microRNA-155 (miR-155) in the hippocampi of an immature rat model of status epilepticus (SE) and children with MTLE. The expressions of TNF-α and miR-155 were significantly upregulated in the seizure-related acute and chronic stages of MTLE in the immature rat model and also in children with MTLE. Modulation of TNF-α expression, either by stimulation using myeloid-related protein (MRP8) or lipopolysaccharide or inhibition using lenalidomide on astrocytes, leads to similar dynamic changes in miR-155 expression. Our study is the first to focus on the dynamic expression pattern of miR-155 in the immature rat of SE lithium-pilocarpine model and children with MTLE and to detect their relationship at the astrocyte level. TNF-α and miR-155, having similar expression patterns in the three stages of MTLE development, and their relationship at the astrocyte level may suggest a direct interactive relationship during MTLE development. Therefore, modulation of the TNF-α/miR-155 axis may be a novel therapeutic target for the treatment of MTLE. PMID:23636891

  12. Seizures of idiopathic generalized epilepsies.

    PubMed

    Durón, Reyna M; Medina, Marco T; Martínez-Juárez, Iris E; Bailey, Julia N; Perez-Gosiengfiao, Katerina Tanya; Ramos-Ramírez, Ricardo; López-Ruiz, Minerva; Alonso, María Elisa; Ortega, Ramón H Castro; Pascual-Castroviejo, Ignacio; Machado-Salas, Jesús; Mija, Lizardo; Delgado-Escueta, Antonio V

    2005-01-01

    Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in the United States, 20% in Mexico, and 8% in Central America. Here, we review seizure phenotypes across IGE syndromes, their response to treatment and advances in molecular genetics that influence nosology. Our review included the Medline database from 1945 to 2005 and our prospectively collected Genetic Epilepsy Studies (GENESS) Consortium database. Generalized seizures occur with different and similar semiologies, frequencies, and patterns, ages at onset, and outcomes in different IGEs, suggesting common neuroanatomical pathways for seizure phenotypes. However, the same seizure phenotypes respond differently to the same treatments in different IGEs, suggesting different molecular defects across syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate juvenile myoclonic epilepsy as a clinical entity. Refined understanding of seizure phenotypes, their semiology, frequencies, and patterns together with the identification of molecular lesions in IGEs continue to accelerate the development of molecular epileptology. PMID:16302874

  13. Comparative profiles of sodium valproate and ethosuximide on electro-behavioural correlates in gamma-hydroxybutyrate and pentylenetetrazol induced absence seizures in rats.

    PubMed

    Kumaresan, S; David, J; Joseph, T

    2000-10-01

    Sodium valproate (VPA) and ethosuximide (ESM) were compared on behavioural and EEG changes in gamma-hydroxybutyrate (GHB) and pentylenetetrazole (PTZ) rat models of Absence Seizures (AS). Both GHB, 100 mg/kg i.p. and PTZ, 20 mg/kg i.p., produced repetitive episodes of staring and immobility with concomitant 6 to 9 Hz spike and wave discharges (SWDs) in the EEG. The parameters used for drug evaluation were the number and duration of SWDs/hour. Though the number of SWDs/hour produced by GHB and PTZ were not significantly different, the duration of SWDs was significantly longer in GHB treated rats (P < 0.001) VPA and ESM, at 200 mg/kg i.p., reduced SWD number and duration in GHB pretreated rats, whereas ESM, 50 mg/kg i.p., was four times more effective than VPA, 200 mg/kg i.p., in the PTZ model. Phenytoin (PHY) 20 and Carbamazepine (CBZ) 10 mg/kg i.p., worsened AS, a feature which has also been reported clinically. Both rat models of experimental AS can be used to defect potential anti-absence activity in new chemical entities. PMID:11214495

  14. Rats with mild bile duct ligation show hepatic encephalopathy with cognitive and motor impairment in the absence of cirrhosis: effects of alcohol ingestion.

    PubMed

    Giménez-Garzó, Carla; Salhi, Dounia; Urios, Amparo; Ruíz-Sauri, Amparo; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2015-02-01

    Studies in animal models allow identifying mechanisms and treatments for cognitive and motor alterations in hepatic encephalopathy (HE). Liver diseases leading to HE in humans have different aetiologies (alcoholic, viral, etc.). The International Society for Hepatic Encephalopathy points out that satisfactory model for HE resulting from alcoholic cirrhosis are lacking. This work aimed to develop and characterize an animal model for HE in alcoholic liver cirrhosis. To potentiate the effects of alcohol on liver we administered it (5, 8 or 10% in drinking water) to rats showing mild liver damage induced by "mild" bile duct ligation (MBDL), obtained by sectioning 3 out of 5 bile ducts. MBDL rats show increased markers of cholestasis and liver damage, hyperammonemia and inflammation. MBDL rats also show motor in-coordination, hypokinesia, impaired learning ability in a Y maze and reduced spatial memory in the Morris water maze. Ingesting 10% ethanol does not induce relevant liver damage in control rats but potentiates liver damage in MBDL rats. In contrast, ethanol did not enhance the biochemical or neurological alterations in MBDL rats. This supports that the combination of certain levels of hyperammonemia and inflammation is enough to induce mild cognitive impairment, even in the absence of liver cirrhosis. Rats with MBDL and MBDL-OH survived more than 3 months, allowing performing long-term studies on cognitive and motor alterations and on underlying mechanisms. MBDL-OH rats are a good model to study the mechanisms of ethanol-induced liver cirrhosis and the factors making the liver susceptible to ethanol damage. PMID:24838616

  15. Mutations in GABAA receptor subunits associated with genetic epilepsies.

    PubMed

    Macdonald, Robert L; Kang, Jing-Qiong; Gallagher, Martin J

    2010-06-01

    Mutations in inhibitory GABAA receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilepsy in infancy (SMEI). These mutations are found in both translated and untranslated gene regions and have been shown to affect the GABAA receptors by altering receptor function and/or by impairing receptor biogenesis by multiple mechanisms including reducing subunit mRNA transcription or stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking. PMID:20308251

  16. Neurite extension of developing noradrenergic neurons is impaired in genetically epilepsy-prone rats (GEPR-3s): an in vitro study on the locus coeruleus.

    PubMed

    Clough, R W; Peterson, B R; Steenbergen, J L; Jobe, P C; Eells, J B; Browning, R A; Mishra, P K

    1998-01-01

    A primary determinant of seizure susceptibility and severity in genetically epilepsy-prone rats (GEPRs), is a generalized deficiency in the central noradrenergic system of these animals. In particular, this deficiency includes reduced numbers of norepinephrine (NE) synaptic terminals in several brain areas and distinctly fewer NE axons within the auditory tectum. Two strains of GEPRs have been developed: GEPR-3s that have moderately severe clonic seizures and GEPR-9s that have severe tonic seizures culminating in complete hindlimb extension. Seizures in animals of each substrain are preceded by a brief episode of wild running. The developmental profile of NE axonal growth in GEPRs compared to control rats is not known, but may be causally related to NE deficiencies in this seizure model. The present study compared developmental neurite extension of fetal NE neurons in vitro between GEPR-3s and Sprague-Dawley control rats, the strain from which GEPR-3s were originally derived. Neurite arborization of individual NE neurons was assessed by quantitative morphometry following immunocytochemical identification of tyrosine hydroxylase (TH). Preliminary studies using explant and dispersed-cell cultures of control-rat tissues showed that optimal culture parameters to support neuritogenesis of LC neurons included the use of dispersed-cell cultures, Pronectin-F substrate, day-14 gestation donor-tissue, no use of cytosine-arabinofuranoside (ARA-c, a glial mitotic inhibitor) and the presence of co-cultured tectal tissue. Compared to fetal control-rat NE neurons co-cultured with fetal control-rat tectum, NE neurons derived from fetal GEPR-3 LC in co-culture with GEPR-3 tectum exhibited only 30% of the neurite extension of control-rat LC neurons and GEPR-3 LC neurons had a similarly deficient amount of branching. This study suggests, but does not prove, that deficiency in tectal NE in GEPR-3s involves a developmental deficiency in neurite extension from GEPR-3 LC neurons

  17. Antiarrhythmic drugs and epilepsy.

    PubMed

    Borowicz, Kinga K; Banach, Monika

    2014-08-01

    For a long time it has been suspected that epilepsy and cardiac arrhythmia may have common molecular background. Furthermore, seizures can affect function of the central autonomic control centers leading to short- and long-term alterations of cardiac rhythm. Sudden unexpected death in epilepsy (SUDEP) has most likely a cardiac mechanism. Common elements of pathogenesis create a basis for the assumption that antiarrhythmic drugs (AADs) may affect seizure phenomena and interact with antiepileptic drugs (AEDs). Numerous studies have demonstrated anticonvulsant effects of AADs. Among class I AADs (sodium channel blockers), phenytoin is an established antiepileptic drug. Propafenone exerted low anti-electroshock activity in rats. Lidocaine and mexiletine showed the anticonvulsant activity not only in animal models, but also in patients with partial seizures. Among beta-blockers (class II AADs), propranolol was anticonvulsant in models for generalized tonic-clonic and complex partial seizures, but not for myoclonic convulsions. Metoprolol and pindolol antagonized tonic-clonic seizures in DBA/2 mice. Timolol reversed the epileptiform activity of pentylenetetrazol (PTZ) in the brain. Furthermore, amiodarone, the representative of class III AADs, inhibited PTZ- and caffeine-induced convulsions in mice. In the group of class IV AADs, verapamil protected mice against PTZ-induced seizures and inhibited epileptogenesis in amygdala-kindled rats. Verapamil and diltiazem showed moderate anticonvulsant activity in genetically epilepsy prone rats. Additionally, numerous AADs potentiated the anticonvulsant action of AEDs in both experimental and clinical conditions. It should be mentioned, however, that many AADs showed proconvulsant effects in overdose. Moreover, intravenous esmolol and intra-arterial verapamil induced seizures even at therapeutic dose ranges. PMID:24948053

  18. Delirium and epilepsy

    PubMed Central

    Kaplan, Peter W.

    2003-01-01

    Delirium (a state of usually reversible global brain disfunction due to toxic, metabolic, or infectious causes) and epilepsy (a condition of spontaneous, recurrent paroxysmal electrical excitation or dysfunction) are becoming increasingly better understood, and hence easier to diagnose and treat. The clinical features of delirium predominantly involve subacute changes in cognition, awareness, and activity levels, behavioral disturbance, clouding consciousness, and sleep-wake cycle changes. In contrast, epilepsy involves the acute interruption of brain function, often with convulsive activity, falls, and injury. States that may share the clinical features of both, such as nonconvulsive epileptic states, are also important: the cause of brain derangement is one of excessive and abnormal electrical brain activity. In such conditions, the clinical manifestations may resemble states of delirium and confusion, and the absence of convulsive clinical activity is significant. Electroencephalography remains the diagnostic test of choice: it is essential for differentiating these two conditions, enabling the distinctly different treatments and epilepsy. Ongoing research and investigation are essential to better understand the abnormal brat mechanisms underlying delirium, and to develop better tools for objective diagnosis. PMID:22034394

  19. 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. PMID:27304613

  20. Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading

    PubMed Central

    2010-01-01

    Background There are safety concerns regarding widespread consumption of phytosterol and phytostanol supplemented food products. The aim of this study was to determine, in the absence of excess dietary salt, the individual effects of excess accumulation of dietary phytosterols and phytostanols on blood pressure in Wistar Kyoto (WKY) inbred rats that have a mutation in the Abcg5 gene and thus over absorb phytosterols and phytostanols. Methods Thirty 35-day old male WKY inbred rats (10/group) were fed a control diet or a diet containing phytosterols or phytostanols (2.0 g/kg diet) for 5 weeks. The sterol composition of the diets, plasma and tissues were analysed by gas chromatography. Blood pressure was measured by the tail cuff method. mRNA levels of several renal blood pressure regulatory genes were measured by real-time quantitative PCR. Results Compared to the control diet, the phytosterol diet resulted in 3- to 4-fold increases in the levels of phytosterols in plasma, red blood cells, liver, aorta and kidney of WKY inbred rats (P < 0.05). The phytostanol diet dramatically increased (> 9-fold) the levels of phytostanols in plasma, red blood cells, liver, aorta and kidney of these rats (P < 0.05). The phytosterol diet decreased cholesterol levels by 40%, 31%, and 19% in liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet decreased cholesterol levels by 15%, 16%, 20% and 14% in plasma, liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet also decreased phytosterol levels by 29% to 54% in plasma and tissues (P < 0.05). Both the phytosterol and phytostanol diets produced significant decreases in the ratios of cholesterol to phytosterols and phytostanols in plasma, red blood cells, liver, aorta and kidney. Rats that consumed the phytosterol or phytostanol diets displayed significant increases in systolic and diastolic blood pressure compared to rats that consumed the control diet (P < 0.05). The phytosterol diet increased renal

  1. Effect of chronic fluoxetine treatment on audiogenic epilepsy, symptoms of anxiety and depression in rats of four lines.

    PubMed

    Sarkissova, K Yu; Fedotova, I B; Surina, N M; Nikolaev, G M; Perepelkina, O V; Poletaeva, I I

    2016-03-01

    Anxiety (Anx) and depression (Dp) levels were evaluated in rats of 4 lines: 2 of them (KM and "4") exhibited audiogenic seizures (AS), and 2 (Wistar and "0") had no AS. In KM rats (with AS), Anx and Dp levels were higher than in Wistars (without AS), while in "4" and "0" rats with the related genetic background but contrasting in AS severity, Anx and Dp indices were not different. Fluoxetine treatment exerted antidepressant effect in all rat lines irrespective of its effect on AS. Thus, phenotypic expression of AS is not directly associated with the mechanisms of Anx and Dp development. PMID:27193875

  2. Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single “cryptic” episode of focal hippocampal excitation in awake rats

    PubMed Central

    Norwood, Braxton A.; Bumanglag, Argyle V.; Osculati, Francesco; Sbarbati, Andrea; Marzola, Pasquina; Nicolato, Elena; Fabene, Paolo F.; Sloviter, Robert S.

    2010-01-01

    In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called “classic hippocampal sclerosis.” No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive “endstage” pathology resulting from years of spontaneous seizures. We posed the alternate hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30-minute episodes of perforant pathway stimulation in Sprague-Dawley rats increased granule cell paired-pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8-hour episode of reduced-intensity stimulation in Long-Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal-onset seizures began 16–25 days post-injury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically “cryptic” excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. PMID

  3. Genetics of idiopathic generalized epilepsies.

    PubMed

    Gardiner, Mark

    2005-01-01

    The idiopathic generalized epilepsies (IGEs) are considered to be primarily genetic in origin. They encompass a number of rare mendelian or monogenic epilepsies and more common forms which are familial but manifest as complex, non-mendelian traits. Recent advances have demonstrated that many monogenic IGEs are ion channelopathies. These include benign familial neonatal convulsions due to mutations in KCNQ2 or KCNQ3, generalized epilepsy with febrile seizures plus due to mutations in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2 associated with several IGE sub-types. There has also been progress in understanding the non-mendelian IGEs. A haplotype in the Malic Enzyme 2 gene, ME2, increases the risk for IGE in the homozygous state. Five missense mutations have been identified in EFHC1 in 6 of 44 families with JME. Rare sequence variants have been identified in CACNA1H in sporadic patients with childhood absence epilepsy in the Chinese Han population. These advances should lead to new approaches to diagnosis and treatment. PMID:16302872

  4. Photodynamic therapy for epilepsy

    NASA Astrophysics Data System (ADS)

    Zusman, Edie; Sidhu, Manpreet; Coon, Valerie; Scott, Nicholas; Bisland, Stuart; Tsukamoto, Tara

    2006-02-01

    Epilepsy is surgically curable if the seizure focus can be localized and does not include areas of eloquent cortex. Because epileptic cells are indistinct from surrounding brain, resection typically includes normal tissue. Using the rat kindling model of epilepsy, we evaluated Photodynamic Therapy (PDT) as a super-selective lesioning technique. We present a series of pilot studies to evaluate: 1) Protoporphyrin IX (PpIX) fluorescence, 2) the efficacy of PDT to raise seizure thresholds, 3) the safety of PDT using behavioral studies, and 4) histologic results. Bipolar electrodes were chronically implanted into the cortex and animals received successive low-level stimulation generating seizures of increasing severity. Following 5-aminolevulinic acid (ALA) administration, fully kindled rats received electrical stimulation to induce a generalized seizure. Animals were irradiated with laser light focused onto a temporal craniectomy. Our results show: 1) an increase in PpIX fluorescence in the seizure group, 2) PDT treated animals failed to demonstrate seizure activity following repeat stimulation, 3) no statistically significant difference between treated and control animals were observed on behavioral tests, 4) histology showed pyknotic hippocampal pyramidal cells in the CA3 region without areas of obvious necrosis. In conclusion, this is the first report of heightened PpIX-mediated fluorescence in epileptic brain. The selective accumulation of PpIX with laser PDT may provide a less invasive and more precise technique for obliteration of epileptic foci. PDT warrants additional research to determine if this technique may augment or replace existing procedures for the surgical management of epilepsy.

  5. Enduring Effects of Early Life Stress on Firing Patterns of Hippocampal and Thalamocortical Neurons in Rats: Implications for Limbic Epilepsy

    PubMed Central

    Ali, Idrish; O'Brien, Patrick; Kumar, Gaurav; Zheng, Thomas; Jones, Nigel C.; Pinault, Didier; French, Chris; Morris, Margaret J.; Salzberg, Michael R.; O'Brien, Terence J.

    2013-01-01

    Early life stress results in an enduring vulnerability to kindling-induced epileptogenesis in rats, but the underlying mechanisms are not well understood. Recent studies indicate the involvement of thalamocortical neuronal circuits in the progression of kindling epileptogenesis. Therefore, we sought to determine in vivo the effects of early life stress and amygdala kindling on the firing pattern of hippocampus as well as thalamic and cortical neurons. Eight week old male Wistar rats, previously exposed to maternal separation (MS) early life stress or early handling (EH), underwent amygdala kindling (or sham kindling). Once fully kindled, in vivo juxtacellular recordings in hippocampal, thalamic and cortical regions were performed under neuroleptic analgesia. In the thalamic reticular nucleus cells both kindling and MS independently lowered firing frequency and enhanced burst firing. Further, burst firing in the thalamic reticular nucleus was significantly increased in kindled MS rats compared to kindled EH rats (p<0.05). In addition, MS enhanced burst firing of hippocampal pyramidal neurons. Following a stimulation-induced seizure, somatosensory cortical neurons exhibited a more pronounced increase in burst firing in MS rats than in EH rats. These data demonstrate changes in firing patterns in thalamocortical and hippocampal regions resulting from both MS and amygdala kindling, which may reflect cellular changes underlying the enhanced vulnerability to kindling in rats that have been exposed to early life stress. PMID:23825595

  6. Elevation of naloxone-sensitive /sup 3/H-dihydromorphine binding in hippocampal formation of genetically epilepsy-prone rats

    SciTech Connect

    Savage, D.D.; Mills, S.A.; Jobe, P.C.; Reigel, C.E.

    1988-01-01

    /sup 3/H-Dihydromorphine (DHM) binding sites were measured in the brain of non-epileptic control and GEPR rats using in vitro autoradiographic techniques. The number of naloxone-sensitive /sup 3/H-DHM binding sites was increased 38-57% in the pyramidal cell layer of ventral hippocampal CA/sub 3/ and CA/sub 1/ of GEPR-3 and GEPR-9 rats compared to non-epileptic controls. No significant differences in /sup 3/H-DHM binding were observed in dorsal hippocampal formation, lateral entorhinal cortex, lateral geniculate or cerebellum. The results suggest that an increase in the number of opioid receptors in ventral hippocampus of GEPR rats may be one factor contributing to the enhanced sensitivity of GEPR-9 rats to the proconvulsant effects of morphine.

  7. Titanium levels in rats implanted with Ti6Al4V treated samples in the absence of wear.

    PubMed

    Rodríguez, D; Gil, F J; Planell, J A; Jorge, E; Alvarez, L; García, R; Larrea, M; Zapata, A

    1999-12-01

    The effect of implantation time and implant nitriding on titanium ion concentration in several tissues of rats carrying Ti6Al4V implants was studied by means of inductively coupled plasma-mass spectroscopy (ICP-MS). Histological studies were also performed in order to check for tissue degeneration due to the Ti6Al4V implantation. The animals were divided into four groups: one received Ti6Al4V implants, the second received nitrided Ti6Al4V implants, the third group received nitrided and descaled Ti6Al4V implants and the last one was the control group. Half the animals of the implanted groups received the Ti6Al4V implant for 30 days, while the other half received the implant for 120 days. Spleen, muscle, kidney, lung, brain and bone samples were retrieved from these rats as well as the control group. Ion concentration measures did not show significant differences between control and implanted rats for the studied period of time, although histological studies showed minor differences, especially on liver tissue samples. PMID:15347963

  8. Treatment of resistant epilepsy.

    PubMed

    Pickrell, William Owen; Smith, Phil E M

    2014-12-01

    Treatment resistance affects around 20% of people with epilepsy and carries a significant comorbidity. It is important to ensure that the diagnosis of epilepsy is secure and the underlying cause of the epilepsy is investigated thoroughly. Management involves early referral for epilepsy surgery when suitable, optimisation of pharmacological treatment, and consideration of comorbidities such as depression. PMID:25468911

  9. High-Frequency Oscillations and Seizure Generation in Neocortical Epilepsy

    ERIC Educational Resources Information Center

    Worrell, Greg A.; Parish, Landi; Cranstoun, Stephen D.; Jonas, Rachel; Baltuch, Gordon; Litt, Brian

    2004-01-01

    Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60--100 Hz) epileptiform oscillations…

  10. Intellectual Disability and Epilepsy in Down Syndrome

    PubMed Central

    BARCA, Diana; TARTA-ARSENE, Oana; DICA, Alice; ILIESCU, Catrinel; BUDISTEANU, Magdalena; MOTOESCU, Cristina; BUTOIANU, Niculina; CRAIU, Dana

    2014-01-01

    Down Syndrome (DS) is the most common genetic cause of mental retardation, with a reported frequency of epilepsy between 1.4-17% (1). There is a paucity of data in the literature regarding epilepsy in Down syndrome and its relation to intellectual disability. Objectives: The purpose of this article is to analyze the association of epilepsy in children with DS - frequency and type of seizures, treatment, outcome and to compare cognitive impairment of children with DS and epilepsy and DS without epilepsy from our cohort. Methods: A four years systematic retrospective analysis of the database of the Pediatric Neurology Clinic (January 2010 - December 2013) identified a cohort of 39 pediatric cases with DS and neurological symptoms, 9 of them (23%) associating epileptic seizures. Following data were analysed: clinical and neurological examination, type/s of seizures, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), psychological examination, psychiatric evaluation in selected cases, electrocardiography (ECG), cardiac ultrasonography, ophthalmologic examination. Results: 23% (9 patients) of the children with DS of our cohort presented epilepsy. Five patients had epileptic spasms (56%), one of these further developed astatic seizures. Focal seizures were observed in three patients (33%) and absence with eyelid myoclonias in one patient (11%). Two of the nine patients with DS and epilepsy had generalized seizures, both with very good response to levetiracetam (LEV). EEG was abnormal at seizure onset, and was improved after treatment. Of the nine children with DS and epilepsy, two (22%) presented mild mental retardation and seven (78%) had moderate to severe cognitive delay. Of the 30 children with DS and without epilepsy, 21 (70%) had mild mental retardation and 9 (30%) had moderate to severe cognitive impairment. Conclusions: The most frequent epileptic syndrome associated with DS is West syndrome, with good response to specific antiepileptics

  11. Neurological morbidity of severe epilepsy.

    PubMed

    Janz, D

    1988-01-01

    The "severity" of a disease is a relative expression and its definition will vary depending on the perspective of the observer. The patient's subjective perception of the disease, the way it is regarded socially by the community, and the doctor's objective assessment rarely coincide. In fact, they are frequently diametrically opposed. As far as the patient's personal perception of epilepsy is concerned, there has apparently been no satisfactory attempt thus far at a systematic grading of the subjective handicap, despite the growth of interest in psychological matters and the self-help movement. Similarly, social ability or disability cannot be adequately assessed on the basis of medical criteria such as frequency and type of seizures. We present a grading system which will serve as an example of an appropriate method of assessing social abilities, and which will permit the patient's occupational potential to be estimated in relation to the risk of accidents resulting from seizures. From the medical point of view, the impairment of a patient's abilities due to epilepsy is a function of the patient's responsiveness to treatment. We present a critical review of the factors which have an effect on the therapeutic prognosis: the causes of epilepsy, underlying structural lesions, the incidence of convulsive status epilepticus, various types of attacks, and the different epileptic syndromes. Taking two examples--epilepsy presenting in the form of absence and epilepsy with complex focal seizures--we show that ultimately the "severity of epilepsy" can only be defined from the medical standpoint on the basis of several factors whose value is of a predictive nature. PMID:3292232

  12. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  13. Convulsant and subconvulsant doses of norfloxacin in the presence and absence of biphenylacetic acid alter extracellular hippocampal glutamate but not gamma-aminobutyric acid levels in conscious rats.

    PubMed

    Smolders, I; Gousseau, C; Marchand, S; Couet, W; Ebinger, G; Michotte, Y

    2002-02-01

    Fluoroquinolones are antibiotics with central excitatory side effects. These adverse effects presumably result from inhibition of gamma-aminobutyric acid (GABA) binding to GABA(A) receptors. This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA). Nevertheless, it remains questionable whether GABA receptor antagonism alone can explain the convulsant activity potentials of these antimicrobial agents. The present study was undertaken to investigate the possible effects of norfloxacin, both in the absence and in the presence of BPAA, on the extracellular hippocampal levels of GABA and glutamate, the main central inhibitory and excitatory amino acid neurotransmitters, respectively. This in vivo microdialysis approach with conscious rats allows monitoring of behavioral alterations and concomitant transmitter modulation in the hippocampus. Peroral administration of 100 mg of BPAA per kg of body weight had no effect on behavior and did not significantly alter extracellular GABA or glutamate concentrations. Intravenous perfusion of 300 mg of norfloxacin per kg did not change the rat's behavior or the concomitant neurotransmitter levels in about half of the experiments, while the remaining animals exhibited severe seizures. These norfloxacin-induced convulsions did not affect extracellular hippocampal GABA levels but were accompanied by enhanced glutamate concentrations. Half of the rats receiving both 100 mg of BPAA per kg and 50 mg of norfloxacin per kg displayed lethal seizures, while the remaining animals showed no seizure-related behavior. In the latter subgroup, again no significant alterations in extracellular GABA levels were observed, but glutamate overflow remained significantly elevated for at least 3 h. In conclusion, norfloxacin exerts convulsant activity in rats, accompanied by elevations of extracellular hippocampal glutamate levels but not GABA levels, even in the presence of BPAA. PMID:11796360

  14. Convulsant and Subconvulsant Doses of Norfloxacin in the Presence and Absence of Biphenylacetic Acid Alter Extracellular Hippocampal Glutamate but Not Gamma-Aminobutyric Acid Levels in Conscious Rats

    PubMed Central

    Smolders, I.; Gousseau, C.; Marchand, S.; Couet, W.; Ebinger, G.; Michotte, Y.

    2002-01-01

    Fluoroquinolones are antibiotics with central excitatory side effects. These adverse effects presumably result from inhibition of γ-aminobutyric acid (GABA) binding to GABAA receptors. This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA). Nevertheless, it remains questionable whether GABA receptor antagonism alone can explain the convulsant activity potentials of these antimicrobial agents. The present study was undertaken to investigate the possible effects of norfloxacin, both in the absence and in the presence of BPAA, on the extracellular hippocampal levels of GABA and glutamate, the main central inhibitory and excitatory amino acid neurotransmitters, respectively. This in vivo microdialysis approach with conscious rats allows monitoring of behavioral alterations and concomitant transmitter modulation in the hippocampus. Peroral administration of 100 mg of BPAA per kg of body weight had no effect on behavior and did not significantly alter extracellular GABA or glutamate concentrations. Intravenous perfusion of 300 mg of norfloxacin per kg did not change the rat's behavior or the concomitant neurotransmitter levels in about half of the experiments, while the remaining animals exhibited severe seizures. These norfloxacin-induced convulsions did not affect extracellular hippocampal GABA levels but were accompanied by enhanced glutamate concentrations. Half of the rats receiving both 100 mg of BPAA per kg and 50 mg of norfloxacin per kg displayed lethal seizures, while the remaining animals showed no seizure-related behavior. In the latter subgroup, again no significant alterations in extracellular GABA levels were observed, but glutamate overflow remained significantly elevated for at least 3 h. In conclusion, norfloxacin exerts convulsant activity in rats, accompanied by elevations of extracellular hippocampal glutamate levels but not GABA levels, even in the presence of BPAA. PMID:11796360

  15. Olfactory neuroepithelium transplanted onto the parietal cortex of rats: electroolfactogram in absence of connections with the host brain.

    PubMed

    Amemori, T; Soukup, T; Bures

    1987-05-01

    A technique, allowing continuous electrophysiological monitoring of the functional properties of transplanted olfactory neuroepithelium is described. Viability of isolated parts of nasal mucosa obtained from adult rats was tested in vitro. Pieces of olfactory neuroepithelium (2 X 2 mm) were transplanted onto the exposed parietal cortex of adult rats and protected by plastic wells covered with a transparent lid. At one-week intervals the lid was removed and the transplanted epithelium was tested for electrical responses to amyl acetate vapours. Reliable electroolfactograms appeared 3 weeks after transplantation and could be elicited in 60% of transplants (n = 15) during the subsequent 6 weeks but disappeared later. Morphological control at the conclusion of the experiment showed that the transplant consisted of pieces of epithelium forming vesicular or semivesicular structures but not containing olfactory sensory neurons and not connected with the host brain. It is concluded that the method allows recording responses of the transplanted neuroepithelium to olfactory stimuli but does not yield a sufficiently stable preparation for establishing ectopic olfactory input to the brain. PMID:3610502

  16. Animal models of epilepsy: use and limitations

    PubMed Central

    Kandratavicius, Ludmyla; Balista, Priscila Alves; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Umeoka, Eduardo Henrique; Garcia-Cairasco, Norberto; Bueno-Junior, Lezio Soares; Leite, Joao Pereira

    2014-01-01

    Epilepsy is a chronic neurological condition characterized by recurrent seizures that affects millions of people worldwide. Comprehension of the complex mechanisms underlying epileptogenesis and seizure generation in temporal lobe epilepsy and other forms of epilepsy cannot be fully acquired in clinical studies with humans. As a result, the use of appropriate animal models is essential. Some of these models replicate the natural history of symptomatic focal epilepsy with an initial epileptogenic insult, which is followed by an apparent latent period and by a subsequent period of chronic spontaneous seizures. Seizures are a combination of electrical and behavioral events that are able to induce chemical, molecular, and anatomic alterations. In this review, we summarize the most frequently used models of chronic epilepsy and models of acute seizures induced by chemoconvulsants, traumatic brain injury, and electrical or sound stimuli. Genetic models of absence seizures and models of seizures and status epilepticus in the immature brain were also examined. Major uses and limitations were highlighted, and neuropathological, behavioral, and neurophysiological similarities and differences between the model and the human equivalent were considered. The quest for seizure mechanisms can provide insights into overall brain functions and consciousness, and animal models of epilepsy will continue to promote the progress of both epilepsy and neurophysiology research. PMID:25228809

  17. Progressive myoclonus epilepsy.

    PubMed

    Girard, Jean-Marie; Turnbull, Julie; Ramachandran, Nivetha; Minassian, Berge A

    2013-01-01

    The progressive myoclonus epilepsies (PMEs) consist of a group of diseases with myoclonic seizures and progressive neurodegeneration, with onset in childhood and/or adolescence. Lafora disease is a neuronal glycogenosis in which normal glycogen is transformed into starch-like polyglucosans that accumulate in the neuronal somatodendritic compartment. It is caused by defects of two genes of yet unknown function, one encoding a glycogen phosphatase (laforin) and the other an ubiquitin E3 ligase (malin). Early cognitive deterioration, visual seizures affecting over half, and slowing down of EEG basic activity are three major diagnostic clues. Unverricht-Lundborg disease is presently thought to be due to damage to neurons by lysosomal cathepsins and reactive oxygen species due to absence of cystatin B, a small protein that inactivates cathepsins and, by ways yet unknown, quenches damaging redox compounds. Preserved cognition and background EEG activity, action myoclonus early morning and vertex spikes in REM sleep are the diagnostic clues. Sialidosis, with cherry-red spot, neuronopathic Gaucher disease, with paralysis of verticality, and ataxia-PME, with ataxia at onset in the middle of the first decade, are also lysosomal diseases. How the lysosomal defect culminates in myoclonus and epilepsy in these conditions remains unknown. PMID:23622396

  18. The Role of Calcium Channels in Epilepsy.

    PubMed

    Rajakulendran, Sanjeev; Hanna, Michael G

    2016-01-01

    A central theme in the quest to unravel the genetic basis of epilepsy has been the effort to elucidate the roles played by inherited defects in ion channels. The ubiquitous expression of voltage-gated calcium channels (VGCCs) throughout the central nervous system (CNS), along with their involvement in fundamental processes, such as neuronal excitability and synaptic transmission, has made them attractive candidates. Recent insights provided by the identification of mutations in the P/Q-type calcium channel in humans and rodents with epilepsy and the finding of thalamic T-type calcium channel dysfunction in the absence of seizures have raised expectations of a causal role of calcium channels in the polygenic inheritance of idiopathic epilepsy. In this review, we consider how genetic variation in neuronal VGCCs may influence the development of epilepsy. PMID:26729757

  19. [Eponyms and epilepsy (history of Eastern civilizations)].

    PubMed

    Janković, S M; Sokić, D V; Lević, Z M; Susić, V; Drulović, J; Stojsavljević, N; Veskov, R; Ivanus, J

    1996-01-01

    The history of eponyms for epilepsy in the lands of the Eastern globe present the portrait of the attitudes of both the laymen and skilled people towards the disease and patient, as well as to the Nature itself. As opposed to the West which during the Middle ages changed its concepts of epilepsy as the organic brain disease for the sublime 'alchemic' position, the people of the East were more prone to consider from the beginning of their civilization till the XIX century that epilepsy is the consequence of the evanescent spiritual and extracorporal forces which by themselves were out of their reach. As compared to the western civilization, the historical resources are, often as a consequence of a linguistic barriers, more scarce-as consequently is the number of eponyms, but are nevertheless picturesque. The medical science from Babylonian period presumed that epileptic manifestations are the consequence of the demonic or ill spiritual actions. There existed an attitude that at the beginning of an epileptic attack the patient was possessed by a demon (the Akkadic, i.e., Babylonian verb "sibtu" denoting epilepsy, had the meaning "to seize" or "to be obsessed"); at the end of the clonic phase the demon departed from the body. Different demons were responsible for different forms of epilepsy such as nocturnal and children epilepsy, absence epilepsy and pure convulsions, simple and complex automatisms, and gelastic epilepsy. Thus, the doctors from the period of Babylon aside from making primordial classification of epilepsies, knew about their clinical picture (prodromal symptoms and aura, Jackson's epilepsy. Todd's paralysis), postictal phenomena and intericatl emotional instability; provocative factors were also known (sleep deprivation, emotions, as well as alcohol, albeit in a negative sense-as a cure for epilepsy). There is no doubt than in the period of Babylon the clinical picture of serial fits and its progress to status epilepticus were clearly recognized and

  20. Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

    2014-01-01

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

  1. Low Level Chlorpyrifos Exposure Increases Anandamide Accumulation in Juvenile Rat Brain in the Absence of Brain Cholinesterase Inhibition

    PubMed Central

    Carr, Russell L.; Graves, Casey A.; Mangum, Lee C.; Nail, Carole A.; Ross, Matthew K.

    2014-01-01

    The prevailing dogma is that chlorpyrifos (CPF) mediates its toxicity through inhibition of cholinesterase (ChE). However, in recent years, the toxicological effects of developmental CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We hypothesize that the endocannabinoid system may be an important target because of its vital role in nervous system development. We have previously reported that repeated exposure to CPF results in greater inhibition of fatty acid amide hydrolase (FAAH), the enzyme that metabolizes the endocannabinoid anandamide (AEA), than inhibition of either forebrain ChE or monoacylglycerol lipase (MAGL), the enzyme that metabolizes the endocannabinoid 2-arachidonylglycerol (2-AG). This exposure resulted in the accumulation of 2-AG and AEA in the forebrain of juvenile rats; however, even at the lowest dosage level used (1.0 mg/kg), forebrain ChE inhibition was still present. Thus, it is not clear if FAAH activity would be inhibited at dosage levels that do not inhibit ChE. To determine this, 10 day old rat pups were exposed daily for 7 days to either corn oil or 0.5 mg/kg CPF by oral gavage. At 4 and 12 h post-exposure on the last day of administration, the activities of serum ChE and carboxylesterase (CES) and forebrain ChE, MAGL, and FAAH were determined as well as the forebrain AEA and 2-AG levels. Significant inhibition of serum ChE and CES was present at both 4 and 12 h. There was no significant inhibition of the activities of forebrain ChE or MAGL and no significant change in the amount of 2-AG at either time point. On the other hand, while no statistically significant effects were observed at 4 h, FAAH activity was significantly inhibited at 12 h resulting in a significant accumulation of AEA. Although it is not clear if this level of accumulation impacts brain maturation, this study demonstrates that developmental CPF exposure at a level that does not inhibit brain ChE can alter components of

  2. Effects of temperature and ethanol on agonist and antagonist binding to rat heart muscarinic receptors in the absence and presence of GTP.

    PubMed Central

    Waelbroeck, M; Robberecht, P; Chatelain, P; De Neef, P; Christophe, J

    1985-01-01

    The effect of temperature on the binding of four agonists and three antagonists to rat heart muscarinic receptors was studied in the absence and presence of GTP. The binding of agonists to two states (or classes) of receptors, in the absence of GTP, led to enthalpy and entropy changes that decreased sharply above 25 degrees C, suggesting that agonists induced 'isomerization' reactions (large conformational changes and/or receptor-effector association). Both temperature increase and ethanol decreased hydrophobic interactions, thereby hindering binding and/or agonist-induced 'isomerization' reactions. Addition of GTP to the incubation medium also appeared to reverse (or prevent) 'isomerization' reactions. For agonist binding to the low-affinity state, in the presence of GTP, and for antagonist binding, the thermodynamic parameters observed could be readily explained by simple receptor-ligand associations; large entropy increases and small enthalpy increases, provoked by hydrophobic and ionic interactions, were partly neutralized by entropy and enthalpy decreases, due to hydrogen bonds and van der Waals interactions. The muscarinic antagonists used (atropine, n-methylscopolamine and dexetimide), being more hydrophobic molecules than the agonists tested (carbamylcholine, oxotremorine and pilocarpine), induced larger entropy changes or more negative enthalpy changes. PMID:4062907

  3. Effects of temperature and ethanol on agonist and antagonist binding to rat heart muscarinic receptors in the absence and presence of GTP.

    PubMed

    Waelbroeck, M; Robberecht, P; Chatelain, P; De Neef, P; Christophe, J

    1985-10-15

    The effect of temperature on the binding of four agonists and three antagonists to rat heart muscarinic receptors was studied in the absence and presence of GTP. The binding of agonists to two states (or classes) of receptors, in the absence of GTP, led to enthalpy and entropy changes that decreased sharply above 25 degrees C, suggesting that agonists induced 'isomerization' reactions (large conformational changes and/or receptor-effector association). Both temperature increase and ethanol decreased hydrophobic interactions, thereby hindering binding and/or agonist-induced 'isomerization' reactions. Addition of GTP to the incubation medium also appeared to reverse (or prevent) 'isomerization' reactions. For agonist binding to the low-affinity state, in the presence of GTP, and for antagonist binding, the thermodynamic parameters observed could be readily explained by simple receptor-ligand associations; large entropy increases and small enthalpy increases, provoked by hydrophobic and ionic interactions, were partly neutralized by entropy and enthalpy decreases, due to hydrogen bonds and van der Waals interactions. The muscarinic antagonists used (atropine, n-methylscopolamine and dexetimide), being more hydrophobic molecules than the agonists tested (carbamylcholine, oxotremorine and pilocarpine), induced larger entropy changes or more negative enthalpy changes. PMID:4062907

  4. Galactosemia and phantom absence seizures.

    PubMed

    Aydin-Özemir, Zeynep; Tektürk, Pınar; Uyguner, Zehra Oya; Baykan, Betül

    2014-01-01

    Generalized and focal seizures can rarely be seen in galactosemia patients, but absence seizures were not reported previously. An 18-year-old male was diagnosed as galactosemia at the age of 8 months. No family history of epilepsy was present. His absence seizures realized at the age of 9 years. Generalized 3-4 Hz spike-wave discharges were identified in his electroencephalography. Homozygous mutation at exon 6 c. 563A > G was identified. The electroencephalogram of his sibling was unremarkable. Our aim was to present the long-term follow-up of a patient diagnosed with galactosemia, who had phantom absence seizures and typical 3-4 Hz spike-wave discharges in his electroencephalogram to draw attention to this rare association. PMID:25624930

  5. Childhood epilepsy and sleep

    PubMed Central

    Al-Biltagi, Mohammed A

    2014-01-01

    Sleep and epilepsy are two well recognized conditions that interact with each other in a complex bi-directional way. Some types of epilepsies have increased activity during sleep disturbing it; while sleep deprivation aggravates epilepsy due to decreased seizure threshold. Epilepsy can deteriorate the sleep-related disorders and at the same time; the parasomnias can worsen the epilepsy. The secretion of sleep-related hormones can also be affected by the occurrence of seizures and supplementation of epileptic patients with some of these sleep-related hormones may have a beneficial role in controlling epilepsy. PMID:25254184

  6. Excitability and responsiveness of rat barrel cortex neurons in the presence and absence of spontaneous synaptic activity in vivo

    PubMed Central

    Altwegg-Boussac, Tristan; Chavez, Mario; Mahon, Séverine; Charpier, Stéphane

    2014-01-01

    The amplitude and temporal dynamics of spontaneous synaptic activity in the cerebral cortex vary as a function of brain states. To directly assess the impact of different ongoing synaptic activities on neocortical function, we performed in vivo intracellular recordings from barrel cortex neurons in rats under two pharmacological conditions generating either oscillatory or tonic synaptic drive. Cortical neurons membrane excitability and firing responses were compared, in the same neurons, before and after complete suppression of background synaptic drive following systemic injection of a high dose of anaesthetic. Compared to the oscillatory state, the tonic pattern resulted in a more depolarized and less fluctuating membrane potential (Vm), a lower input resistance (Rm) and steeper relations of firing frequency versus injected current (F–I). Whatever their temporal dynamics, suppression of background synaptic activities increased mean Vm, without affecting Rm, and induced a rightward shift of F–I curves. Both types of synaptic drive generated a high variability in current-induced firing rate and patterns in cortical neurons, which was much reduced after removal of spontaneous activity. These findings suggest that oscillatory and tonic synaptic patterns differentially facilitate the input–output function of cortical neurons but result in a similar moment-to-moment variability in spike responses to incoming depolarizing inputs. PMID:24732430

  7. Epilepsy and Mood

    MedlinePlus

    ... Editors David C. Spencer, MD Steven Karceski, MD Epilepsy and mood Update Steven Karceski, MD In their ... important and worrisome topic for peo- ple with epilepsy. In short, a patient may wonder, “ Will the ...

  8. American Epilepsy Society

    MedlinePlus

    ... and pricing here . View the preliminary program here . Epilepsy Currents Generic Substitution of AEDs: Is it Time ... in a multicenter prospective infantile spasms cohort More Epilepsy Professional News AES Releases New Guildeline for Treatment ...

  9. Listening to Epilepsy.

    ERIC Educational Resources Information Center

    Brunquell, Phillip J.

    1994-01-01

    This paper discusses what epilepsy is and what it is not, defines types of epileptic seizures, identifies epilepsy syndromes, discusses antiepileptic drugs, describes seizure surgery, and examines issues of quality of life. (JDD)

  10. Surgery for childhood epilepsy

    PubMed Central

    Jayalakshmi, Sita; Panigrahi, Manas; Nanda, Subrat Kumar; Vadapalli, Rammohan

    2014-01-01

    Approximately 60% of all patients with epilepsy suffer from focal epilepsy syndromes. In about 15% of these patients, the seizures are not adequately controlled with antiepileptic drugs; such patients are potential candidates for surgical treatment and the major proportion is in the pediatric group (18 years old or less). Epilepsy surgery in children who have been carefully chosen can result in either seizure freedom or a marked (>90%) reduction in seizures in approximately two-thirds of children with intractable seizures. Advances in structural and functional neuroimaging, neurosurgery, and neuroanaesthesia have improved the outcomes of surgery for children with intractable epilepsy. Early surgery improves the quality of life and cognitive and developmental outcome and allows the child to lead a normal life. Surgically remediable epilepsies should be identified early and include temporal lobe epilepsy with hippocampal sclerosis, lesional temporal and extratemporal epilepsy, hemispherical epilepsy, and gelastic epilepsy with hypothalamic hamartoma. These syndromes have both acquired and congenital etiologies and can be treated by resective or disconnective surgery. Palliative procedures are performed in children with diffuse and multifocal epilepsies who are not candidates for resective surgery. The palliative procedures include corpus callosotomy and vagal nerve stimulation while deep brain stimulation in epilepsy is still under evaluation. For children with “surgically remediable epilepsy,” surgery should be offered as a procedure of choice rather than as a treatment of last resort. PMID:24791093

  11. Musicogenic epilepsy.

    PubMed Central

    Brien, S E; Murray, T J

    1984-01-01

    A case of musicogenic epilepsy is reported in which the seizures were precipitated by singing voices. It was found that some singers' voices were particularly epileptogenic and that some of their songs, but not others, would precipitate a seizure. A study of the "offending" songs and singers did not reveal a common key, chord, harmonic interval, pitch or rhythm, and the emotional feeling or intensity of the music did not seem to be relevant. However, the voices that caused the seizures had a throaty, "metallic" quality. Such a singing voice results from incorrect positioning of the larynx such that it is not allowed to descend fully during singing; consequently, the vowel sounds produced must be manipulated by the lips or jaw to be distinguished. This trait is most common in singers with a low voice range who sing softly and use a microphone. It is not seen in trained operatic or musical theatre singers. The results of repeated testing showed that the seizures in this patient were caused by listening to singers who positioned the larynx incorrectly. PMID:6498678

  12. Current and emerging treatments for absence seizures in young patients

    PubMed Central

    Vrielynck, Pascal

    2013-01-01

    In this report, we review the pharmacological and non-pharmacological treatments of the different absence seizure types as recently recognized by the International League Against Epilepsy: typical absences, atypical absences, myoclonic absences, and eyelid myoclonia with absences. Overall, valproate and ethosuximide remain the principal anti-absence drugs. Typical absence seizures exhibit a specific electroclinical semiology, pathophysiology, and pharmacological response profile. A large-scale comparative study has recently confirmed the key role of ethosuximide in the treatment of childhood absence epilepsy, more than 50 years after its introduction. No new antiepileptic drug has proven major efficacy against typical absences. Of the medications under development, brivaracetam might be an efficacious anti-absence drug. Some experimental drugs also show efficacy in animal models of typical absence seizures. The treatment of other absence seizure types is not supported with a high level of evidence. Rufinamide appears to be the most promising new antiepileptic drug for atypical absences and possibly for myoclonic absences. The efficacy of vagal nerve stimulation should be further evaluated for atypical absences. Levetiracetam appears to display a particular efficacy in eyelid myoclonia with absences. Finally, it is important to remember that the majority of antiepileptic drugs, whether they be old or new, may aggravate typical and atypical absence seizures. PMID:23885176

  13. Association of Microtubule Dynamics with Chronic Epilepsy.

    PubMed

    Xu, Xin; Hu, Yida; Xiong, Yan; Li, Zhonggui; Wang, Wei; Du, Chao; Yang, Yong; Zhang, Yanke; Xiao, Fei; Wang, Xuefeng

    2016-09-01

    Approximately 30 % of epilepsy cases are refractory to current pharmacological treatments through unknown mechanisms. Much work has been done on the role of synaptic components in the pathogenesis of epilepsy, but relatively little attention has been given to the potential role of the microtubules. We investigated the level of microtubule dynamic in 30 human epileptic tissues and two different chronic epilepsy rat models. The administration of microtubule-modulating agent attenuated the progression of chronic epilepsy. By contrast, microtubule-depolymerizing agent aggravated the progression of chronic epilepsy. The electrophysiological index by whole-cell clamp was used to investigate the neuronal excitation and inhibitory synaptic transmission in brain slices after administration of microtubule-modulating agent and microtubule-depolymerizing agent. Interestingly, we found that microtubule-modulating agent significantly increased the frequency of action potential firing in interneurons, and significantly promoted the amplitudes and frequencies of miniature inhibitory postsynaptic currents. Microtubule-depolymerizing agent had an opposite effect. These findings suggest that modulating hyperdynamic microtubules may take an anti-epileptic effect via postsynaptic mechanisms in interneurons. It could represent a potential pharmacologic target in epilepsy treatment. PMID:26377107

  14. Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus.

    PubMed

    Miller, Laurence L; Altarifi, Ahmad A; Negus, S Stevens

    2015-10-01

    Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. PMID:26375515

  15. Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

    PubMed Central

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  16. Effects of site-specific infusions of methionine sulfoximine on the temporal progression of seizures in a rat model of mesial temporal lobe epilepsy.

    PubMed

    Dhaher, Roni; Wang, Helen; Gruenbaum, Shaun E; Tu, Nathan; Lee, Tih-Shih W; Zaveri, Hitten P; Eid, Tore

    2015-09-01

    Glutamine synthetase (GS) in astrocytes is critical for metabolism of glutamate and ammonia in the brain, and perturbations in the anatomical distribution and activity of the enzyme are likely to adversely affect synaptic transmission. GS is deficient in discrete regions of the hippocampal formation in patients with mesial temporal lobe epilepsy (MTLE), a disorder characterized by brain glutamate excess and recurrent seizures. To investigate the role of site-specific inhibition of GS in MTLE, we chronically infused the GS inhibitor methionine sulfoximine (MSO) into one of the following areas of adult laboratory rats: (1) the angular bundle, n=6; (2) the deep entorhinal cortex (EC), n=7; (3) the stratum lacunosum-moleculare of CA1, n=7; (4) the molecular layer of the subiculum, n=10; (5) the hilus of the dentate gyrus, n=6; and (6) the lateral ventricle, n=6. Twelve animals were infused with phosphate buffered saline (PBS) into the same areas to serve as controls. All infusions were unilateral, and animals were monitored by continuous video-intracranial EEG recordings for 3 weeks to capture seizure activity. All animals infused with MSO into the entorhinal-hippocampal area exhibited recurrent seizures that were particularly frequent during the first 3 days of infusion and that continued to recur for the entire 3 week recording period. Only a fraction of animals infused with MSO into the lateral ventricle had recurrent seizures, which occurred at a lower frequency compared with the other MSO infused group. Infusion of MSO into the hilus of the dentate gyrus resulted in the highest total number of seizures over the 3-week recording period. Infusion of MSO into all brain regions studied, with the exception of the lateral ventricle, led to a change in the composition of seizure severity over time. Low-grade (stages 1-3) seizures were more prevalent early during infusion, while severe (stages 4-5) seizures were more prevalent later. Thus, the site of GS inhibition within

  17. Mutant GABA(A) receptor subunits in genetic (idiopathic) epilepsy.

    PubMed

    Hirose, Shinichi

    2014-01-01

    The γ-aminobutyric acid receptor type A (GABAA receptor) is a ligand-gated chloride channel that mediates major inhibitory functions in the central nervous system. GABAA receptors function mainly as pentamers containing α, β, and either γ or δ subunits. A number of antiepileptic drugs have agonistic effects on GABAA receptors. Hence, dysfunctions of GABAA receptors have been postulated to play important roles in the etiology of epilepsy. In fact, mutations or genetic variations of the genes encoding the α1, α6, β2, β3, γ2, or δ subunits (GABRA1, GABRA6, GABRB2, GABRB3, GABRG2, and GABRD, respectively) have been associated with human epilepsy, both with and without febrile seizures. Epilepsy resulting from mutations is commonly one of following, genetic (idiopathic) generalized epilepsy (e.g., juvenile myoclonic epilepsy), childhood absence epilepsy, genetic epilepsy with febrile seizures, or Dravet syndrome. Recently, mutations of GABRA1, GABRB2, and GABRB3 were associated with infantile spasms and Lennox-Gastaut syndrome. These mutations compromise hyperpolarization through GABAA receptors, which is believed to cause seizures. Interestingly, most of the insufficiencies are not caused by receptor gating abnormalities, but by complex mechanisms, including endoplasmic reticulum (ER)-associated degradation, nonsense-mediated mRNA decay, intracellular trafficking defects, and ER stress. Thus, GABAA receptor subunit mutations are now thought to participate in the pathomechanisms of epilepsy, and an improved understanding of these mutations should facilitate our understanding of epilepsy and the development of new therapies. PMID:25194483

  18. [Epilepsy care network].

    PubMed

    Otsuki, Taisuke

    2014-05-01

    Build-up of community health coalition system is now an essential part of medicine. However, little attention has been paid to epilepsy care in Japan, which resulted in a chaotic and difficult situation to find epilepsy-care physicians in the community. The reason is that responsible medical specialty in charge has been ambiguous historically in Japan and a lack of post-in-charge in the government to plan epilepsy care system is aggravating this condition. To solve this issue, epilepsy care network connecting the primary, secondary and tertiary epilepsy care physicians should be established and open to the community. In this context, our Epilepsy Care Network-Japan was started on July 2012 proposing a new epilepsy care algorithm suitable for our complex medical community. PMID:24912299

  19. Acute and chronic pharmacological models of generalized absence seizures.

    PubMed

    Cortez, Miguel A; Kostopoulos, George K; Snead, O Carter

    2016-02-15

    This article reviews the contribution of pharmacologically induced acute and chronic animal models to our understanding of epilepsies featuring non-convulsive generalized seizures, the typical and atypical absence seizures. Typical absences comprise about 5% of all epilepsies regardless of age and the atypical ones are even more common. Although absence epilepsy was thought to be relatively benign, children with childhood epilepsy (CAE) turn out to have a high rate of pretreatment attention deficits that persist despite seizure freedom. The phenomenon of the absence seizure has long attracted research interest because of the clear temporal relationship of the conspicuous EEG rhythm of 3 Hz generalized spike and wave discharges (GSWD) and the parallel transient "loss of consciousness" characterizing these seizures which is time-locked with the GSWD. Indeed, clinical epileptologists, basic scientists and neurophysiologists have long recognized in GSWD a unique electrographic and behavioral marker of the genetic predisposition to most types of epilepsy. Interestingly, the subject is still controversial since it has recently been proposed that both classification terms of CAE currently in use: idiopathic and primary generalized, be abandoned - a point of debate. Both issues - underlying mechanisms and focal origin of absence seizures - may be further enlightened by observations in valid animal models. PMID:26343323

  20. [Current management of epilepsy].

    PubMed

    Mizobuchi, Masahiro

    2013-09-01

    Epilepsy is one of the most common neurological disorders. Global neurological knowledge is essential for differential diagnosis of epileptic syndromes due to the diversity of ictal semiology, causes and syndromes. Neurologists play an important role in planning the medical care for patients with epilepsy, as medication is the most fundamental therapeutic strategy. Some patients with early-onset epilepsy require joint care by pediatric neurologists, those with intractable epilepsy by neurosurgeons, and those with psychological comorbidity by psychiatrists, and neurologists should play a coordinating role. While there is a great need for neurologists to participate in epilepsy care, neurologists in Japan currently do not participate substantially in the epilepsy management system. It is necessary to train more neurologists who can provide epilepsy care and conduct basic and clinical research on epilepsy by providing continuous education on epilepsy for general neurologists as well as pre- and post-graduate medical students. Most of the patients who require long-term treatment experience many medical problems and social handicaps, such as adverse effects of medication, social stigma, educational disadvantages and difficulties in obtaining driver's license. To improve the quality of life of patients with epilepsy, it is desirable to build broad medical-social networks participated by patients, doctors, neurological nurses, psychologists, social workers, school teachers, managers of employment support facilities and care givers. PMID:24018740

  1. The mean age of petit mal epilepsy

    PubMed Central

    Syeda, Afsarunnesa; Karim, Md. Rezaul

    2016-01-01

    Objective: Petit mal epilepsy or absence seizures involve brief, sudden lapses of consciousness and most often occurs in people under age of 20 years. This study was done to find out the most likely significant age affected by petit mal epilepsy and whether they had higher rate of behavioral, educational, and social problems. Materials and Methods: We run tests on total 32 patients (male 16 and female 16) from newborns to 20 years of age. Results: The most affected ages were from 4 to 9 years and both genders were equally affected. They have higher rate of behavioral, educational, and social problems, and most likely recovering ages from the disease were from 15 to 20 years. Conclusion: These findings could contribute in diagnosis and treatment of Petit Mal Epilepsy, as it often misinterpreted as daydreaming or inattention.

  2. Genetics Home Reference: Northern epilepsy

    MedlinePlus

    ... Understand Genetics Home Health Conditions Northern epilepsy Northern epilepsy Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Northern epilepsy is a genetic condition that causes recurrent seizures ( ...

  3. Christianity and epilepsy.

    PubMed

    Owczarek, K; Jędrzejczak, J

    2013-01-01

    Epileptic seizures have been known from time immemorial. Throughout the ages, however, ideas concerning the aetiology and treatment of epilepsy have changed considerably. Epilepsy is mentioned many times in the Pentateuch, where it is portrayed as a mysterious condition, whose symptoms, course and contingencies evade rational laws and explanations. In the Middle Ages, the accepted view which prevailed in social consciousness was that patients with epilepsy were possessed by Satan and other impure spirits. One common method of treatment of epileptic seizures was to submit the patient to cruel exorcisms. Patients were frequently injured in the process and some of them even died. Our understanding of epilepsy and its social consequences has improved considerably within the last century. The most significant progress as far as diagnosis and treatment of epilepsy is concerned took place in the last four decades of the twentieth century. Although we now know much more about epilepsy than we used to, this knowledge is still insufficiently popularized. PMID:23821425

  4. Pediatric epilepsy syndromes.

    PubMed

    Wirrell, Elaine; Nickels, Katherine C

    2010-06-01

    Epilepsy syndromes denote specific constellations of clinical seizure type(s), EEG findings, and other characteristic clinical features. Most syndromes recognized in epilepsy are genetic and developmental disorders that begin in the pediatric years. Epilepsy syndromes are divided into idiopathic (primary) types, in which the presumed etiology is genetic, versus symptomatic (secondary) types, in which there is either an underlying etiology that is known or presumed based on other evidence of brain dysfunction. Epilepsies are also classified by those with generalized seizures and those with localization-related seizures. Identification of a specific syndrome is important to define the best treatment and accurately prognosticate long-term outcome for children with epilepsy. In this chapter, clinical and electrographic features as well as inheritance patterns of common pediatric epilepsy syndromes are discussed. PMID:22810315

  5. Sleep, epilepsy, and autism.

    PubMed

    Accardo, Jennifer A; Malow, Beth A

    2015-06-01

    The purpose of this review article is to explore the links between sleep and epilepsy and the treatment of sleep problems in children with autism spectrum disorder (ASD). Epilepsy and sleep have bidirectional relationships, and problems with both are highly prevalent in children with ASD. Literature is reviewed to support the view that sleep is particularly important to address in the context of ASD. Identification and management of sleep disorders may improve seizure control and challenging behaviors. In closing, special considerations for evaluating and treating sleep disorders in children with ASD and epilepsy are reviewed. This article is part of a Special Issue entitled "Autism and Epilepsy". PMID:25496798

  6. PCDH19-related epilepsy and Dravet Syndrome: Face-off between two early-onset epilepsies with fever sensitivity.

    PubMed

    Trivisano, Marina; Pietrafusa, Nicola; Ciommo, Vincenzo di; Cappelletti, Simona; Palma, Luca de; Terracciano, Alessandra; Bertini, Enrico; Vigevano, Federico; Specchio, Nicola

    2016-09-01

    Aim of this study is to compare PCDH19-related epilepsy and Dravet Syndrome (DS) in order to find out differences between these two infantile epilepsies with fever sensitivity. We retrospectively reviewed the medical records of 15 patients with PCDH19-related epilepsy and 19 with DS. Comparisons were performed with Fisher's exact test or Student's t-test. Females prevailed in PCDH19-related epilepsy. Epilepsy onset was earlier in DS (5.0+2.1 vs 11.2+7.0months; p<0.05). The second seizure/cluster occurred after a longer latency in PCDH19-related epilepsy rather than in DS (10.1±13.6 vs 2.2±2.1months; p<0.05). Seizures were mainly single and prolonged seizures in DS, and brief and clustered in PCDH19-related epilepsy. Myoclonic and clonic seizures have been found only in DS. Other types of seizures were found in both epilepsies with a prevalence of GTCS and atypical absences in DS, and focal motor and hypomotor seizures in PCDH19-related epilepsy. Seizures with affective symptoms have been confirmed to be typical of PCDH19-related epilepsy. Status Epilepticus equally occurred in both groups. Photosensitivity was detected only in DS. No differences were found about the presence of intellectual disabilities and behavioral disturbances. We were able to find out some distinctive features, which could address the diagnosis towards DS or PCDH19-related epilepsy, since first manifestation. These considerations suggest to definitively considering PCDH19 gene as cause of a proper epileptic phenotype. PMID:27371789

  7. Investigation of the possible association of NEDD4-2 (NEDD4L) gene with idiopathic photosensitive epilepsy.

    PubMed

    Vanli-Yavuz, Ebru Nur; Ozdemir, Ozkan; Demirkan, Ayse; Catal, Suzin; Bebek, Nerses; Ozbek, Ugur; Baykan, Betul

    2015-09-01

    NEDD4-2 alias NEDD4L (neural precursor cell expressed, developmentally downregulated) gene was reported as a candidate gene for epileptic photo-sensitivity. We aimed to investigate this possible association of NEDD4-2 variants with idiopathic photosensitive epilepsy. Consecutive patients who had been followed up at our epilepsy center and diagnosed with idiopathic epilepsy according to ILAE criteria and clear-cut photoparoxysmal responses in their electroencephalograms and 100 ethnically matched healthy subjects were included in the study. The regions around previously reported three variants, namely, S233L, E271A and H515P were tracked with DHPLC and the samples showing variations were sequenced. 81 patients (63 females) aged between 12-63 years (45 had juvenile myoclonic epilepsy, 11 childhood absence epilepsy, 14 juvenile absence epilepsy, 7 late onset idiopathic generalized epilepsy, 1 unclassified idiopathic generalized epilepsy, and 3 patients with idiopathic photosensitive occipital lobe epilepsy) were included in this study. We found only one heterozygous S233L variant in a 23-year-old man who has photosensitive form of juvenile absence epilepsy and pattern sensitivity to striped carpets. Other two variants were not found in any of the other patients and controls. Our results suggest that three screened NEDD4-2 variants do not play a leading role in the pathogenesis of photosensitive epilepsy in the Turkish population. PMID:25542253

  8. Genes, Seizures & Epilepsy

    ERIC Educational Resources Information Center

    Goldman, Alica M.

    2006-01-01

    The chance that someone will develop any disease is influenced by heredity and environment. Epilepsy is not an exception. Everybody inherits a unique degree of susceptibility to seizures. About 3 percent of the United States population is prone to seizures and will get epilepsy at some point of their lives (1). Two thirds of the people with…

  9. Epilepsy and Life Performance

    ERIC Educational Resources Information Center

    Rodin, Ernst A.; And Others

    1977-01-01

    To aid in developing classifications of epileptics that would be predictive of day to day functioning, 369 epileptics were classified as having epilepsy only or epilepsy associated with intellectual disturbances or organic mental syndrome, other neurological handicap, or behavioral problems. (GW)

  10. Epilepsy treatment and creativity.

    PubMed

    Zubkov, Sarah; Friedman, Daniel

    2016-04-01

    Creativity can be defined as the ability to understand, develop, and express, in a systematic fashion, novel orderly relationships. It is sometimes difficult to separate cognitive skills requisite for the creative process from the drive that generates unique new ideas and associations. Epilepsy itself may affect the creative process. The treatment of epilepsy and its comorbidities, by altering or disrupting the same neural networks through antiseizure drugs (ASDs), treatment of epilepsy comorbidities, ablative surgery, or neurostimulation may also affect creativity. In this review, we discuss the potential mechanisms by which treatment can influence the creative process and review the literature on the consequences of therapy on different aspects of creativity in people with epilepsy. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID:26831642

  11. Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures.

    PubMed

    Venzi, Marcello; David, François; Bellet, Joachim; Cavaccini, Anna; Bombardi, Cristiano; Crunelli, Vincenzo; Di Giovanni, Giuseppe

    2016-09-01

    Absence seizures (ASs) are the hallmark of childhood/juvenile absence epilepsy. Monotherapy with first-line anti-absence drugs only controls ASs in 50% of patients, indicating the need for novel therapeutic targets. Since serotonin family-2 receptors (5-HT2Rs) are known to modulate neuronal activity in the cortico-thalamo-cortical loop, the main network involved in AS generation, we investigated the effect of selective 5-HT2AR and 5-HT2CR ligands on ASs in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well established polygenic rat model of these non-convulsive seizures. GAERS rats were implanted with fronto-parietal EEG electrodes under general anesthesia, and their ASs were later recorded under freely moving conditions before and after intraperitoneal administration of various 5-HT2AR and 5-HT2CR ligands. The 5-HT2A agonist TCB-2 dose-dependently decreased the total time spent in ASs, an effect that was blocked by the selective 5-HT2A antagonist MDL11,939. Both MDL11,939 and another selective 5-HT2A antagonist (M100,907) increased the length of individual seizures when injected alone. The 5-HT2C agonists lorcaserin and CP-809,101 dose-dependently suppressed ASs, an effect blocked by the selective 5-HT2C antagonist SB 242984. In summary, 5-HT2ARs and 5-HT2CRs negatively control the expression of experimental ASs, indicating that selective agonists at these 5-HT2R subtypes might be potential novel anti-absence drugs. PMID:27085605

  12. Experimental absence seizures: potential role of gamma-hydroxybutyric acid and GABAB receptors.

    PubMed

    Bernasconi, R; Lauber, J; Marescaux, C; Vergnes, M; Martin, P; Rubio, V; Leonhardt, T; Reymann, N; Bittiger, H

    1992-01-01

    We have investigated whether the pathogenesis of spontaneous generalized non-convulsive seizures in rats with genetic absence epilepsy is due to an increase in the brain levels of gamma-hydroxybutyric acid (GHB) or in the rate of its synthesis. Concentrations of GHB or of its precursor gamma-butyrolactone (GBL) were measured with a new GC/MS technique which allows the simultaneous assessment of GHB and GBL. The rate of GHB synthesis was estimated from the increase in GHB levels after inhibition of its catabolism with valproate. The results of this study do not indicate significant differences in GHB or GBL levels, or in their rates of synthesis in rats showing spike-and-wave discharges (SWD) as compared to rats without SWD. Binding data indicate that GHB, but not GBL, has a selective, although weak affinity for GABAB receptors (IC50 = 150 microM). Similar IC50 values were observed in membranes prepared from rats showing SWD and from control rats. The average GHB brain levels of 2.12 +/- 0.23 nmol/g measured in the cortex and of 4.28 +/- 0.90 nmol/g in the thalamus are much lower than the concentrations necessary to occupy a major part of the GABAB receptors. It is unlikely that local accumulations of GHB reach concentrations 30-70-fold higher than the average brain levels. After injection of 3.5 mmol/kg GBL, a dose sufficient to induce SWD, brain concentrations reach 240 +/- 31 nmol/g (Snead, 1991) and GHB could thus stimulate the GABAB receptor. Like the selective and potent GABAB receptor agonist R(-)-baclofen, GHB causes a dose-related decrease in cerebellar cGMP. This decrease and the increase in SWD caused by R(-)-baclofen were completely blocked by the selective and potent GABAB receptor antagonist CGP 35348, whereas only the increase in the duration of SWD induced by GHB was totally antagonized by CGP 35348. The decrease in cerebellar cGMP levels elicited by GHB was only partially antagonized by CGP 35348. These findings suggest that all effects of R

  13. Infections, inflammation and epilepsy.

    PubMed

    Vezzani, Annamaria; Fujinami, Robert S; White, H Steve; Preux, Pierre-Marie; Blümcke, Ingmar; Sander, Josemir W; Löscher, Wolfgang

    2016-02-01

    Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled "epilepsy." Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered. PMID:26423537

  14. Prevalence and associated features of epilepsy in adults with Down's syndrome.

    PubMed

    McVicker, R W; Shanks, O E; McClelland, R J

    1994-04-01

    The aim of this study was to establish the prevalence of epilepsy in persons with Down's syndrome aged 19 years and over. A total of 191 adults with Down's syndrome were identified, giving a prevalence of 0.76/1000 (95% CI 0.75 to 0.77). Of these, 18 had epilepsy, giving a prevalence of 9.4% (95% CI 5.3% to 13.5%). The prevalence of epilepsy increased with age, reaching 46% in those over 50. The neurophysiological (EEG) findings of the epilepsy group were compared with those of a control group of Down's syndrome adults without epilepsy. Paroxysmal abnormalities consistent with a diagnosis of epilepsy were found in 80% of the epilepsy group, compared with only 13% of controls (P < 0.001). Epilepsy of late onset was associated with diffuse EEG abnormalities and clinical evidence of dementia. The age distribution and EEG findings suggest two independent processes in the causation of epilepsy: late-onset epilepsy associated with clinical evidence of dementia, and early-onset epilepsy in the absence of dementia. PMID:8038944

  15. Magnetoencephalography in pediatric epilepsy

    PubMed Central

    Kim, Hunmin; Chung, Chun Kee

    2013-01-01

    Magnetoencephalography (MEG) records the magnetic field generated by electrical activity of cortical neurons. The signal is not distorted or attenuated, and it is contactless recording that can be performed comfortably even for longer than an hour. It has excellent and decent temporal resolution, especially when it is combined with the patient's own brain magnetic resonance imaging (magnetic source imaging). Data of MEG and electroencephalography are not mutually exclusive and it is recorded simultaneously and interpreted together. MEG has been shown to be useful in detecting the irritative zone in both lesional and nonlesional epilepsy surgery. It has provided valuable and additive information regarding the lesion that should be resected in epilepsy surgery. Better outcomes in epilepsy surgery were related to the localization of the irritative zone with MEG. The value of MEG in epilepsy surgery is recruiting more patients to epilepsy surgery and providing critical information for surgical planning. MEG cortical mapping is helpful in younger pediatric patients, especially when the epileptogenic zone is close to the eloquent cortex. MEG is also used in both basic and clinical research of epilepsy other than surgery. MEG is a valuable diagnostic modality for diagnosis and treatment, as well as research in epilepsy. PMID:24244211

  16. Autoimmune and inflammatory epilepsies.

    PubMed

    Nabbout, Rima

    2012-09-01

    The role of immunity and inflammation in epilepsy have long been suggested by the anticonvulsant activity of steroids in some infancy and childhood epilepsies. The role of fever and infection in exacerbating seizures due to possible proinflammatory molecules, the increased frequency of seizures in systemic autoimmune diseases like systemic lupus erythematous, and, recently, the detection of autoantibodies in some unexplained epilepsies reinforced the causal place of immunity and inflammation in epilepsies with unknown etiology. In this article, we summarize epilepsies where clinical and biologic data strongly support the pathogenic role of autoantibodies (e.g., limbic encephalitides, N-methyl-d-aspartate [NMDA] encephalitis) and epilepsies where immune-mediated inflammation occurs, but the full pathogenic cascade is either not clear (e.g., Rasmussen's encephalitis) or only strongly hypothesized (idiopathic hemiconvulsion-hemiplegia syndrome [IHHS] and fever-induced refractory epilepsy in school-aged children [FIRES]). We emphasize the electroclinical features that would help to diagnose these conditions, allowing early immunomodulating therapy. Finally, we raise some questions that remain unclear regarding diagnosis, mechanisms, and future therapies. PMID:22946722

  17. Mitochondrial disease and epilepsy.

    PubMed

    Rahman, Shamima

    2012-05-01

    Mitochondrial respiratory chain disorders are relatively common inborn errors of energy metabolism, with a combined prevalence of one in 5000. These disorders typically affect tissues with high energy requirements, and cerebral involvement occurs frequently in childhood, often manifesting in seizures. Mitochondrial diseases are genetically heterogeneous; to date, mutations have been reported in all 37 mitochondrially encoded genes and more than 80 nuclear genes. The major genetic causes of mitochondrial epilepsy are mitochondrial DNA mutations (including those typically associated with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS] and myoclonic epilepsy with ragged red fibres [MERRF] syndromes); mutations in POLG (classically associated with Alpers syndrome but also presenting as the mitochondrial recessive ataxia syndrome [MIRAS], spinocerebellar ataxia with epilepsy [SCAE], and myoclonus, epilepsy, myopathy, sensory ataxia [MEMSA] syndromes in older individuals) and other disorders of mitochondrial DNA maintenance; complex I deficiency; disorders of coenzyme Q(10) biosynthesis; and disorders of mitochondrial translation such as RARS2 mutations. It is not clear why some genetic defects, but not others, are particularly associated with seizures. Epilepsy may be the presenting feature of mitochondrial disease but is often part of a multisystem clinical presentation. Mitochondrial epilepsy may be very difficult to manage, and is often a poor prognostic feature. At present there are no curative treatments for mitochondrial disease. Individuals with mitochondrial epilepsy are frequently prescribed multiple anticonvulsants, and the role of vitamins and other nutritional supplements and the ketogenic diet remain unproven. PMID:22283595

  18. Art and epilepsy surgery.

    PubMed

    Ladino, Lady Diana; Hunter, Gary; Téllez-Zenteno, José Francisco

    2013-10-01

    The impact of health and disease has led many artists to depict these themes for thousands of years. Specifically, epilepsy has been the subject of many famous works, likely because of the dramatic and misunderstood nature of the clinical presentation. It often evokes religious and even mythical processes. Epilepsy surgical treatment has revolutionized the care of selected patients and is a relatively recent advance. Epilepsy surgery has been depicted in very few artistic works. The first portrait showing a potential surgical treatment for patients with epilepsy was painted in the 12th century. During the Renaissance, Bosch famously provided artistic commentary on traditional beliefs in "The stone of madness". Several of these works demonstrate a surgeon extracting a stone from a patient's head, at one time believed to be the source of all "folly", including epileptic seizures, psychosis, intellectual disability, depression, and a variety of other illnesses. There are some contemporary art pieces including themes around epilepsy surgery, all of them depicting ancient Inca Empire procedures such as trepanning. This article reviews the most relevant artistic works related with epilepsy surgery and also its historical context at the time the work was produced. We also present a painting from the Mexican artist Eduardo Urbano Merino that represents the patient's journey through refractory epilepsy, investigations, and ultimately recovery. Through this work, the artist intends to communicate hope and reassurance to patients going through this difficult process. PMID:23933914

  19. Epilepsy is Dancing.

    PubMed

    Tuft, Mia; Gjelsvik, Bergljot; Nakken, Karl O

    2015-10-01

    In "Epilepsy is Dancing", in Antony and the Johnsons' album "The Crying Light"(2009), the lyrics and accompanying music video depicts an epileptic seizure in which the person is transferred to another beautiful and magical world. This may be called "enchanted epilepsy"; i.e., the experience of epilepsy as deeply nourishing and (positively) transforming, is conveyed not only in the lyrics but also the visual and auditory qualities of the video. The seizure in the video gives associations to Shakespeare's "A Midsummer Night's dream". If epilepsy appears in music lyrics, the focus is mostly on negative aspects of the illness, such as horror, fear and repulsive sexuality associated with the fits [1,2]. Contradictory to these lyrics, Anthony and the Johnsons' song is an example of a positive portrayal of epilepsy. It is open to a multitude of meanings, emotional valence and appraisal of epilepsy. By widening the experiential range associated with epileptic seizures, these lyrics highlight the inherently construed nature of epileptic experience. The song stands out in several ways. First, it describes epilepsy in positive terms, prioritising the euphoric, ecstatic, potentially empowering and enhancing aspects of epileptic seizures. Second, the lyrics and accompanying video point to divine experiences associated with epileptic seizures. Through the lyrics and the music video we are, as an audience, able to sense a snicket of an epileptic seizure, but also the universal experience of loosing control. PMID:26398488

  20. PRRT2 mutation in Japanese children with benign infantile epilepsy.

    PubMed

    Okumura, Akihisa; Shimojima, Keiko; Kubota, Tetsuo; Abe, Shinpei; Yamashita, Shintaro; Imai, Katsumi; Okanishi, Tohru; Enoki, Hideo; Fukasawa, Tatsuya; Tanabe, Takuya; Dibbens, Leanne M; Shimizu, Toshiaki; Yamamoto, Toshiyuki

    2013-08-01

    Mutations in PRRT2 genes have been identified as a major cause of benign infantile epilepsy and/or paroxysmal kinesigenic dyskinesia. We explored mutations in PRRT2 in Japanese patients with BIE as well as its related conditions including convulsion with mild gastroenteritis and benign early infantile epilepsy. We explored PRRT2 mutations in Japanese children who had had unprovoked infantile seizures or convulsion with mild gastroenteritis. The probands included 16 children with benign infantile epilepsy, 6 children with convulsions with mild gastroenteritis, and 2 siblings with benign early infantile epilepsy. In addition, we recruited samples from family members when PRRT2 mutation was identified in the proband. Statistical analyses were performed to identify differences in probands with benign infantile epilepsy according to the presence or absence of PRRT2 mutation. Among a total of 24 probands, PRRT2 mutations was identified only in 6 probands with benign infantile epilepsy. A common insertion mutation, c.649_650insC, was found in 5 families and a novel missense mutation, c.981C>G (I327M), in one. The family history of paroxysmal kinesigenic dyskinesia was more common in probands with PRRT2 mutations than in those without mutations. Our study revealed that PRRT2 mutations are common in Japanese patients with benign infantile epilepsy, especially in patients with a family history of paroxysmal kinesigenic dyskinesia. PMID:23131349

  1. Mitochondrial diseases and epilepsy.

    PubMed

    Bindoff, Laurence A; Engelsen, Bernt A

    2012-09-01

    The mitochondrial respiratory chain is the final common pathway for energy production. Defects affecting this pathway can give rise to disease that presents at any age and affects any tissue. However, irrespective of genetic defect, epilepsy is common and there is a significant risk of status epilepticus. This review summarizes our current understanding of the epilepsy that occurs in mitochondrial disease, focusing on three of the most common disorders: mitochondrial myopathy encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy and ragged-red fibers (MERRF), and polymerase gamma (POLG) related disease. In addition, we review the pathogenesis and possible treatment of these disorders. PMID:22946726

  2. Epilepsy and law.

    PubMed

    Beran, Roy G

    2008-05-01

    Epilepsy can define who one is rather than the diagnosis one has. It may be considered under the rubric of disability with legislative protection against discrimination. Those seeking remedy should investigate alternative dispute resolution in preference to litigation. Many areas of the life of a person with epilepsy deserve examination when considering epilepsy and law. Just some of these include: duty of care; informed consent; driving; research; social interactions; insurance; recreational pursuits; employment; and privacy. This article examines the legal implications and ramifications of these selected topics, acknowledging that the limited scope of the article has only exposed the tip of the iceberg to encourage further exploration. PMID:18234559

  3. Seizure and Psychosocial Outcomes of Childhood and Juvenile Onset Generalized Epilepsies: Wolf in Sheep's Clothing, or Well-Dressed Wolf?

    PubMed

    Nickels, Katherine

    2015-01-01

    Studies of generalized electroclinical syndromes can provide guidance regarding long-term seizure, cognitive, and psychosocial outcomes. Childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and idiopathic generalized epilepsy with generalized tonic-clonic seizures alone are electroclinical syndromes typically associated with normal intellect and good response to antiseizure medications. However, studies have demonstrated significantly poorer psychosocial outcomes than expected for these syndromes, regardless of seizure control. Potential causes for this include underlying abnormalities in social skills, social stigma, and underlying abnormalities in brain development and maturation. PMID:26316843

  4. MRI volumetry shows increased anterior thalamic volumes in patients with absence seizures.

    PubMed

    Betting, Luiz Eduardo; Mory, Susana Barreto; Lopes-Cendes, Iscia; Li, Li Min; Guerreiro, Marilisa M; Guerreiro, Carlos A M; Cendes, Fernando

    2006-05-01

    The interaction between thalamus and cortex appears to be critical to the pathophysiology of idiopathic generalized epilepsies (IGEs). The objective of this study was to investigate thalamic volumes of a group of patients with IGEs using high-resolution MRI. Thalamic segmentation was performed by the same rater, who was unaware of the diagnosis. Thalamic volumes were divided into anterior half and posterior half. One hundred forty-seven patients were scanned (71 with juvenile myoclonic epilepsy, 49 with generalized tonic-clonic seizures only, and 27 with absence epilepsy). Subgroup analyses with corrections for multiple comparisons showed that, when compared with those of controls, anterior thalamic volumes were increased in patients with absence epilepsy and juvenile myoclonic epilepsy with absence seizures, but not in patients with generalized tonic-clonic seizures only and juvenile myoclonic epilepsy without absence seizures. Our results demonstrated that the anterior thalamus is structurally different in patients with IGEs and absence seizures as compared with patients with IGEs without absence seizures. PMID:16530016

  5. Epilepsy: new advances.

    PubMed

    Moshé, Solomon L; Perucca, Emilio; Ryvlin, Philippe; Tomson, Torbjörn

    2015-03-01

    Epilepsy affects 65 million people worldwide and entails a major burden in seizure-related disability, mortality, comorbidities, stigma, and costs. In the past decade, important advances have been made in the understanding of the pathophysiological mechanisms of the disease and factors affecting its prognosis. These advances have translated into new conceptual and operational definitions of epilepsy in addition to revised criteria and terminology for its diagnosis and classification. Although the number of available antiepileptic drugs has increased substantially during the past 20 years, about a third of patients remain resistant to medical treatment. Despite improved effectiveness of surgical procedures, with more than half of operated patients achieving long-term freedom from seizures, epilepsy surgery is still done in a small subset of drug-resistant patients. The lives of most people with epilepsy continue to be adversely affected by gaps in knowledge, diagnosis, treatment, advocacy, education, legislation, and research. Concerted actions to address these challenges are urgently needed. PMID:25260236

  6. Neuropsychological advocacy and epilepsy.

    PubMed

    Loring, David W; Hermann, Bruce P; Cohen, Morris J

    2010-04-01

    Neuropsychologists are in a unique position to be active advocates for patients with epilepsy given their unique understanding of the behavioral and cognitive effects associated the disease, its progression, and its treatment. Neuropsychologists communicate the cognitive and behavioral consequences of epilepsy and its long-term implications to patients, family, school, and employers. In this article we review factors influencing the neuropsychological profile of patients with epilepsy, and discuss common behavioral comorbidities, as well as special issues associated with school placement and long-term planning. We also include a seizure action plan, which is designed to be both an educational tool for individuals with limited epilepsy knowledge, and a way to minimize stigma associated with an event should a seizure occur during school or work. PMID:19214828

  7. The Student with Epilepsy.

    ERIC Educational Resources Information Center

    Anspaugh, David J.; And Others

    1980-01-01

    This article discusses epilepsy, its treatment, and its effects for teachers who have epileptic students in their classes. Epileptic students must be made to feel that they can participate in all facets of school life. (CJ)

  8. Epilepsy and Pregnancy

    MedlinePlus

    ... pregnant women who don't have epilepsy. These complications include: Vaginal bleeding The possibility that your seizures may occur more often Preeclampsia (a condition during pregnancy that is a combination ...

  9. Epilepsy or seizures - discharge

    MedlinePlus

    ... Fenichel GM, Jankovic J, Mazziotta JC, eds. Bradley's Neurology in Clinical Practice . 6th ed. Philadelphia, PA: Elsevier ... Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology . 2009 Jul14;73( ...

  10. Magnetoencephalography and Epilepsy Research

    NASA Astrophysics Data System (ADS)

    Rose, D. F.; Smith, P. D.; Sato, S.

    1987-10-01

    Magnetoencephalography is the detection of the magnetic field distribution across the surface of the head, which is generated by a neuronal discharge within the brain. Magnetoencephalography is used in clinical epilepsy to localize the epileptogenic region prior to its surgical removal. A discussion of the instrumentation based on the superconducting quantum interference device that is used for detecting the magnetic field distribution, the analytical techniques, current research, and future directions of magnetoencephalography in epilepsy research is presented.

  11. 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. PMID:26786403

  12. Glucose metabolism transporters and epilepsy: only GLUT1 has an established role.

    PubMed

    Hildebrand, Michael S; Damiano, John A; Mullen, Saul A; Bellows, Susannah T; Oliver, Karen L; Dahl, Hans-Henrik M; Scheffer, Ingrid E; Berkovic, Samuel F

    2014-02-01

    The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy. PMID:24483274

  13. [Epilepsy and Szondi test].

    PubMed

    Andrade, L

    1976-05-01

    After having briefly recalled the different studies of epilepsy done on the basis of the Szondi test, the author proposes to study the drive structure of three groups of epileptics (19 cases of primary generalized epilepsy, 18 cases of partial temporal lobe epilepsy, 31 cases of partial non-temporal epilepsy) with the purpose of finding possible differences in psychological drive among the three groups and, at the same time, evaluating the test's capacity for discrimination by using the statistical method. The three groups show the same type of profile generally characterized by an extreme need for acceptance and affection (h + !, C- + !) counteracted by a strong repression (hy - !, k -) resulting in agressiveness (s + !). However, statistical analysis (chi square test), the drive formula, the drive class and the EKP showed that, beyond this shared area, there are differences among the three groups. The author then attempts to sort out the meaning of these differences. Finally, based on certain passages from Szondi as well as the test results, the author puts forward an hypothesis linking the psychological drive problematic in primary generalized epilepsies to a very early disturbance in the history of the individual's psychic development, the origins of which would go back to a split in the unity between mother and child. On the other hand, drive disturbances in partial epilepsies would be considered secondary to the illness. PMID:788602

  14. Epilepsy and homicide

    PubMed Central

    Pandya, Neil S; Vrbancic, Mirna; Ladino, Lady Diana; Téllez-Zenteno, José F

    2013-01-01

    Purpose We report the rare case of a patient with intractable epilepsy and escalating aggression, resulting in murder, who had complete resolution of her seizures and explosive behavior following a right temporal lobectomy. Patients and methods We searched the available literature from 1880 to 2013 for cases of epilepsy being used as a court defense for murder and collected information regarding the final sentencing outcomes. We selected 15 papers with a total of 50 homicides. Results We describe the case of a 47-year-old woman with drug-resistant right temporal epilepsy who developed increasing emotional lability, outbursts of anger and escalating violent behavior culminating in a violent murder. The patient was imprisoned while awaiting trial. In the interim, she underwent a successful temporal lobectomy with full resolution of seizures, interictal rage and aggressive behaviors. After the surgery, her charges were downgraded and she was transferred to a psychiatric facility. Conclusion The aggressive behavior associated with epilepsy has been described in the literature for over a century. A link between epilepsy and aggression has been disproportionally emphasized. These patients share some common characteristics: they are usually young men with a long history of epilepsy and lower than average intelligence. The violent act is postictal, sudden-onset, more likely to occur after a cluster of seizures and is usually related with alcohol abuse. PMID:23700367

  15. Epilepsy, cognition and behavior.

    PubMed

    Gulati, Sheffali; Yoganathan, Sangeetha; Chakrabarty, Biswaroop

    2014-10-01

    Epilepsy is defined as two or more unprovoked seizures. Epileptic patients have intellectual disability and behavioral co-morbidities to the tune of up to 25 and 75% respectively. Various factors like underlying etiology, socioeconomic environment at home, age at onset, seizure semiology, seizure descriptors like duration, severity and frequency, therapy related adverse effects secondary to antiepileptic drugs and epilepsy surgery have been implicated for the causation of cognitive and behavioral impairment in epilepsy. Cognitive epilepsy has emerged as a specific entity. This may manifest as a transient behavioral or cognitive change, insidous onset subacute to chronic encephalopathy or more catastrophic in the form of nonconvulsive status epilepticus. Cognitive impairment seen in epileptic children include difficulties in learning, memory, problem solving as well as concept formation. Anxiety, depression and attention deficit hyperkinetic disorders are the most common psychiatric co-morbidities seen. Investigating a child with epilepsy for cognitive and behavioral impairment is difficult as these tests would require cooperation from the patient's side to a significant extent. A rational approach towards treatment would be judicious selection of antiepileptic drugs, treatment of underlying cause, appropriate management of behavioral co-morbidities including psychopharmacotherapy and a trial of immunotherapy (particularly in cognitive epilepsies), wherever appropriate. PMID:25073691

  16. A critical evaluation of the gamma-hydroxybutyrate (GHB) model of absence seizures.

    PubMed

    Venzi, Marcello; Di Giovanni, Giuseppe; Crunelli, Vincenzo

    2015-02-01

    Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the γ-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs. PMID:25403866

  17. A Critical Evaluation of the Gamma-Hydroxybutyrate (GHB) Model of Absence Seizures

    PubMed Central

    Venzi, Marcello; Di Giovanni, Giuseppe; Crunelli, Vincenzo

    2015-01-01

    Typical absence seizures (ASs) are nonconvulsive epileptic events which are commonly observed in pediatric and juvenile epilepsies and may be present in adults suffering from other idiopathic generalized epilepsies. Our understanding of the pathophysiological mechanisms of ASs has been greatly advanced by the availability of genetic and pharmacological models, in particular the γ-hydroxybutyrate (GHB) model which, in recent years, has been extensively used in studies in transgenic mice. GHB is an endogenous brain molecule that upon administration to various species, including humans, induces not only ASs but also a state of sedation/hypnosis. Analysis of the available data clearly indicates that only in the rat does there exist a set of GHB-elicited behavioral and EEG events that can be confidently classified as ASs. Other GHB activities, particularly in mice, appear to be mostly of a sedative/hypnotic nature: thus, their relevance to ASs requires further investigation. At the molecular level, GHB acts as a weak GABA-B agonist, while the existence of a GHB receptor remains elusive. The pre- and postsynaptic actions underlying GHB-elicited ASs have been thoroughly elucidated in thalamus, but little is known about the cellular/network effects of GHB in neocortex, the other brain region involved in the generation of ASs. PMID:25403866

  18. Absence of Change in Total Daily Energy Expenditure (EE(sub TD)) in Young and Mature Rats During 14 Days of Hypergravity

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Moran, M. M.; Stein, T. P.; Hoban-Higgins, T. M.; Fuller, P.; Fuller, C. A.; Dalton, Bonnie P. (Technical Monitor)

    1999-01-01

    Effect of age on the response of EE(sub TD) to an increase in gravity was assessed in young (Y; 1.5 month old) and mature (M; 8 month old) Sprague-Dawley rats. Rats were implanted with transmitters to monitor activity, and metabolism was determined by the double labeled water technique. Daily food intake was measured. For each age, rats (n=8 per treatment) were exposed to centrifugation at 2G, or remained at 1G. There was a difference in EE(sub TD) between age groups, 182 plus or minus 11 and 143 plus or minus 5 kcal/kg/day in Y and M, respectively. This difference was attributed in part to a lower activity level in M animals, 48% of Y rats. After day 6 there was no effect on EE(sub TD) of exposure to 2G, or on food intake per 100g BW. Prior studies show a 20% increase in resting EE with hypergravity. In our study the level of activity was reduced to 41% of 1G in both age groups during 2G. For Y at 1G resting EE accounted for 78% of the EE(sub TD) and activity 22%, while at 2G resting EE was 96% of EE(sub TD) and activity 4%. M rats had similar changes. Independent of age, with exposure to hypergravity EE(sub TD) is maintained by behavioral changes.

  19. Obesity and its association with generalised epilepsy, idiopathic syndrome, and family history of epilepsy.

    PubMed

    Ladino, Lady D; Hernández-Ronquillo, Lizbeth; Téllez-Zenteno, José F

    2014-09-01

    Aim. Previous studies support the concept that obesity is a common comorbid condition in patients with epilepsy (PWE). In this study, we present the body mass index (BMI) and data from a survey to assess physical activity in a sample of PWE from an epilepsy clinic. Methods. Between June of 2011 and January of 2013, 100 PWE from an adult epilepsy clinic were included. We obtained BMI, waist circumference, and information regarding physical activity using a standardised questionnaire. Clinical, demographic, electrographic, and imaging parameters were collected from charts. Results. Mean age of patients was 40 ± 14 (18-77) years. The BMI distribution was as follows: 2 patients (2%) underweight, 26 (26%) normal weight, 34 (34%) overweight, 25 (25%) obese, and 13 (13%) with morbid obesity. In our study, obesity was defined as having a BMI ≥ 30. We found 38 (38%) patients in this range. There was no difference in the rate of drug-resistant epilepsy between obese and non-obese patients (55 vs. 55%; p=0.05). Leisure time habit was reported in 82% of obese patients and 79% of patients without obesity. Overall, the most frequent activity was walking (70%). Factors associated with obesity were generalised epilepsy (OR: 2.7, 1.1-6.6; p=0.012), idiopathic syndrome (OR: 2.7, 1.04-7; p=0.018), and family history of epilepsy (OR: 6.1, 1.5-24.2; p=0.002). Conclusion. Our study suggests an association between obesity, idiopathic generalised epilepsy, and family history of epilepsy. Our study shows that PWE are physically active and there is no clear relation between exercise and obesity. We could not identify any association between drug-resistant epilepsy and obesity. Absence of direct comparison with a control non-epileptic population; a cross-sectional design not allowing evaluation of a causal association among variables; and reliance on self-reported physical activity are to be considered as limitations of the present study. PMID:25179745

  20. Using Relevance Feedback to Distinguish the Changes in EEG During Different Absence Seizure Phases.

    PubMed

    Li, Jing; Liu, Xianzeng; Ouyang, Gaoxiang

    2016-07-01

    We carried out a series of statistical experiments to explore the utility of using relevance feedback on electroencephalogram (EEG) data to distinguish between different activity states in human absence epilepsy. EEG recordings from 10 patients with absence epilepsy are sampled, filtered, selected, and dissected from seizure-free, preseizure, and seizure phases. A total of 112 two-second 19-channel EEG epochs from 10 patients were selected from each phase. For each epoch, multiscale permutation entropy of the EEG data was calculated. The feature dimensionality was reduced by linear discriminant analysis to obtain a more discriminative and compact representation. Finally, a relevance feedback technique, that is, direct biased discriminant analysis, was applied to 68 randomly selected queries over nine iterations. This study is a first attempt to apply the statistical analysis of relevance feedback to the distinction of different EEG activity states in absence epilepsy. The average precision in the top 10 returned results was 97.5%, and the standard deviation suggested that embedding relevance feedback can effectively distinguish different seizure phases in absence epilepsy. The experimental results indicate that relevance feedback may be an effective tool for the prediction of different activity states in human absence epilepsy. The simultaneous analysis of multichannel EEG signals provides a powerful tool for the exploration of abnormal electrical brain activity in patients with epilepsy. PMID:25245133

  1. Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

    PubMed Central

    Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

    2014-01-01

    Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

  2. Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy.

    PubMed

    Carletti, Fabio; Gambino, Giuditta; Rizzo, Valerio; Ferraro, Giuseppe; Sardo, Pierangelo

    2016-05-01

    The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our results showed that the TRPV1 agonist, capsaicin, increased epileptic outcomes; whilst antagonizing TRPV1 with capsazepine exerts a protective role on paroxysmal discharge. When capsaicin is co-administered with WIN effective dose of 10mg/kg is able to reduce its antiepileptic strength, especially on the triggering of MDA response. Accordingly, capsazepine at the protective dose of 2mg/kg managed to potentiate WIN antiepileptic effects, when co-treated. Moreover, WIN subeffective dose of 5mg/kg was turned into effective when capsazepine comes into play. This evidence suggests that systemic administration of TRPV1-active drugs influences electrically induced epilepsy, with a noticeable protective activity for capsazepine. Furthermore, results from the pharmacological interaction with WIN support an interplay between cannabinoid and TRPV1 signaling that could represent a promising approach for a future pharmacological strategy to challenge hyperexcitability-based diseases. PMID:26970948

  3. ADHD, Methylphenidate, and Childhood Epilepsy.

    PubMed

    Sharma, Rahul; Plioplys, Sigita

    2016-06-01

    Investigators from the Department of Functional Neurology, Epileptology and Epilepsy Institute (IDEE), and the Lyon's University Hospital examined the clinical determinants of ADHD severity in children with epilepsy (CWE) along with the response to treatment with methylphenidate (MPH). PMID:27617408

  4. 77 FR 59197 - Epilepsy Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-26

    ... HUMAN SERVICES Health Resources and Services Administration Epilepsy Program AGENCY: Health Resources... to the Epilepsy Foundation of America. SUMMARY: The Health Resources and Services Administration will be issuing noncompetitive supplemental funding under the Maternal and Child Health Bureau's...

  5. Voxel-based morphometry in patients with idiopathic generalized epilepsies.

    PubMed

    Betting, Luiz Eduardo; Mory, Susana Barreto; Li, Li Min; Lopes-Cendes, Iscia; Guerreiro, Marilisa M; Guerreiro, Carlos A M; Cendes, Fernando

    2006-08-15

    Idiopathic generalized epilepsies (IGE) are a group of frequent age-related epilepsy syndromes. IGE are clinically characterized by generalized tonic-clonic, myoclonic and absence seizures. According to predominant seizure type and age of onset, IGE are divided in subsyndromes: childhood absence and juvenile absence epilepsy (AE), juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures on awakening (GTCS). The limits between these subsyndromes are not well defined, supporting the existence of only one major syndrome. Visual assessment of routine magnetic resonance imaging (MRI) in patients with IGE is normal. MRI voxel-based morphometry (VBM) uses automatically segmented gray and white matter for comparisons, eliminating the investigator bias. We used VBM to study 120 individuals (47 controls, 44 with JME, 24 with AE and 15 with GTCS) to investigate the presence of subtle structural abnormalities in IGE subsyndromes. VBM was performed searching for abnormalities on gray matter concentration (GMC) between patients groups and controls. Compared to controls, JME presented increased GMC in frontobasal region and AE showed increased GMC in the superior mesiofrontal region. The GTCS group did not differ from controls. There were no areas of reduced GMC with the statistical level selected. Region of interest analysis showed increased GMC in the anterior portion of the thalamus in patients with absence seizures. Our results support subtle GMC abnormalities in patients with JME and AE when compared to controls. These findings suggest the existence of different patterns of cortical abnormalities in IGE subsyndromes. PMID:16702001

  6. In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats.

    PubMed

    Hurst, Robert E; Van Gordon, Samuel; Tyler, Karl; Kropp, Bradley; Towner, Rheal; Lin, HsuehKung; Marentette, John O; McHowat, Jane; Mohammedi, Ehsan; Greenwood-Van Meerveld, Beverley

    2016-05-01

    Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 ± 1.1 vs. 2.6 ± 1.1 vs 1.2 ± 0.5 and 1.01 ± 0.7 kΩ·cm(2) in the PS-treated and ChABC-treated rat bladders (P = 0.0016 and P = 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. PMID:26911855

  7. Rational management of epilepsy.

    PubMed

    Viswanathan, Venkataraman

    2014-09-01

    Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country. PMID:24871077

  8. Epilepsy and physical exercise.

    PubMed

    Pimentel, José; Tojal, Raquel; Morgado, Joana

    2015-02-01

    Epilepsy is one of the commonest neurologic diseases and has always been associated with stigma. In the interest of safety, the activities of persons with epilepsy (PWE) are often restricted. In keeping with this, physical exercise has often been discouraged. The precise nature of a person's seizures (or whether seizures were provoked or unprovoked) may not have been considered. Although there has been a change in attitude over the last few decades, the exact role of exercise in inducing seizures or aggravating epilepsy still remains a matter of discussion among experts in the field. Based mainly on retrospective, but also on prospective, population and animal-based research, the hypothesis that physical exercise is prejudicial has been slowly replaced by the realization that physical exercise might actually be beneficial for PWE. The benefits are related to improvement of physical and mental health parameters and social integration and reduction in markers of stress, epileptiform activity and the number of seizures. Nowadays, the general consensus is that there should be no restrictions to the practice of physical exercise in people with controlled epilepsy, except for scuba diving, skydiving and other sports at heights. Whilst broader restrictions apply for patients with uncontrolled epilepsy, individual risk assessments taking into account the seizure types, frequency, patterns or triggers may allow PWE to enjoy a wide range of physical activities. PMID:25458104

  9. 5-HT1A receptor gene silencers Freud-1 and Freud-2 are differently expressed in the brain of rats with genetically determined high level of fear-induced aggression or its absence.

    PubMed

    Kondaurova, Elena M; Ilchibaeva, Tatiana V; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2016-09-01

    Serotonin 5-HT1A receptor is known to play a crucial role in the mechanisms of genetically defined aggression. In its turn, 5-HT1A receptor functional state is under control of multiple factors. Among others, transcriptional factors Freud-1 and Freud-2 are known to be involved in the repression of 5-HT1A receptor gene expression. However, implication of these factors in the regulation of behavior is unclear. Here, we investigated the expression of 5-HT1A receptor and silencers Freud-1 and Freud-2 in the brain of rats selectively bred for 85 generations for either high level of fear-induced aggression or its absence. It was shown that Freud-1 and Freud-2 levels were different in aggressive and nonaggressive animals. Freud-1 protein level was decreased in the hippocampus, whereas Freud-2 protein level was increased in the frontal cortex of highly aggressive rats. There no differences in 5-HT1A receptor gene expression were found in the brains of highly aggressive and nonaggressive rats. However, 5-HT1A receptor protein level was decreased in the midbrain and increased in the hippocampus of highly aggressive rats. These data showed the involvement of Freud-1 and Freud-2 in the regulation of genetically defined fear-induced aggression. However, these silencers do not affect transcription of the 5-HT1A receptor gene in the investigated rats. Our data indicate the implication of posttranscriptional rather than transcriptional regulation of 5-HT1A receptor functional state in the mechanisms of genetically determined aggressive behavior. On the other hand, the implication of other transcriptional regulators for 5-HT1A receptor gene in the mechanisms of genetically defined aggression could be suggested. PMID:27150226

  10. Factors affecting epilepsy development and epilepsy prognosis in cerebral palsy.

    PubMed

    Mert, Gulen Gul; Incecik, Faruk; Altunbasak, Sakir; Herguner, Ozlem; Mert, Mustafa Kurthan; Kiris, Nurcihan; Unal, Ilker

    2011-08-01

    A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy. PMID:21763948

  11. The Epilepsy Foundation's 4th Biennial Epilepsy Pipeline Update Conference.

    PubMed

    French, Jacqueline A; Schachter, Steven C; Sirven, Joseph; Porter, Roger

    2015-05-01

    On June 5 and 6, 2014, the Epilepsy Foundation held its 4th Biennial Epilepsy Pipeline Update Conference, an initiative of the Epilepsy Therapy Project, which showcased the most promising epilepsy innovations from health-care companies and academic laboratories dedicated to pioneering and advancing drugs, biologics, technologies, devices, and diagnostics for epilepsy. Speakers and attendees included emerging biotech and medical technology companies, major pharmaceutical and device companies, as well as investigators and innovators at the cutting-edge of epilepsy. The program included panel discussions on collaboration between small and large companies, how to get products in need of funding to the marketplace, who is currently funding epilepsy and CNS innovation, and how the NIH facilitates early-stage drug development. Finally, the conference featured the third annual "Shark Tank" competition. The presentations are summarized in this paper, which is followed by a compilation of the meeting poster abstracts. PMID:25922152

  12. Medical Marijuana for Epilepsy?

    PubMed

    Kolikonda, Murali K; Srinivasan, Kavitha; Enja, Manasa; Sagi, Vishwanath; Lippmann, Steven

    2016-01-01

    Treatment-refractory epilepsy remains an important clinical problem. There is considerable recent interest by the public and physicians in using medical marijuana or its derivatives to treat seizures. The endocannabinoid system has a role in neuronal balance and ictal control. There is clinical evidence of success in diminishing seizure frequencies with cannabis derivatives, but also documentation about exacerbating epilepsy or of no discernible effect. There are lay indications and anecdotal reports of success in attenuating the severity of epilepsy, but without solid investigational corroboration. Marijuana remains largely illegal, and may induce adverse consequences. Clinical applications are not approved, thus are restricted and only recommended in selected treatment unresponsive cases, with appropriate monitoring. PMID:27354925

  13. Cannabinoids and Epilepsy.

    PubMed

    Rosenberg, Evan C; Tsien, Richard W; Whalley, Benjamin J; Devinsky, Orrin

    2015-10-01

    Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies. PMID:26282273

  14. Neuroimaging of epilepsy.

    PubMed

    Cendes, Fernando; Theodore, William H; Brinkmann, Benjamin H; Sulc, Vlastimil; Cascino, Gregory D

    2016-01-01

    Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454

  15. Gliotoxin causes apoptosis and necrosis of rat Kupffer cells in vitro and in vivo in the absence of oxidative stress: Exacerbation by caspase and serine protease inhibition

    PubMed Central

    Anselmi, Kristin; Stolz, Donna B.; Nalesnik, Michael; Watkins, Simon C.; Kamath, Ravindra; Gandhi, Chandrashekhar R.

    2009-01-01

    Background/Aims A potential application of gliotoxin therapy for liver fibrosis was suggested by its apoptotic effect on fibrogenic activated stellate cells. We investigated if gliotoxin exerts similar effects on hepatic macrophages Kupffer cells. Methods Effects of gliotoxin on Kupffer cells isolated from the normal liver and in vivo following its administration to CCl4–induced cirrhotic rats were studied. Results Gliotoxin caused apoptosis of cultured Kupffer cells, the effect being apparent at 0.3 μM concentration within 1 hour; longer incubation caused necrosis. This effect was associated with mitochondroial cytochrome c release, caspase-3 activation and ATP depletion. Interestingly, inhibition of caspase-3 and serine proteases accelerated and augmented gliotoxin-induced cell death via necrosis. Gliotoxin stimulated nuclear translocation of NFκB, and phosphorylation of p38, ERK1/2 and JNK MAP kinases, but these signaling molecules were not involved in gliotoxin-induced death of Kupffer cells. In vivo administration of gliotoxin to cirrhotic rats caused apoptosis of Kupffer cells, stellate cells and hepatocytes. In control rats, the effect was minimal on the nonparenchymal cells and not apparent on hepatocytes. Conclusions In the fibrotic liver, gliotoxin nonspecifically causes death of hepatic cell types. Modification of gliotoxin molecule may be necessary for selective targeting and elimination of activated stellate cells. PMID:17466404

  16. Emu Oil Reduces Small Intestinal Inflammation in the Absence of Clinical Improvement in a Rat Model of Indomethacin-Induced Enteropathy

    PubMed Central

    Abimosleh, Suzanne M.; Tran, Cuong D.; Howarth, Gordon S.

    2013-01-01

    Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. Aim. We investigated EO for its potential to attenuate NSAID-enteropathy in rats. Methods. Male Sprague Dawley rats (n = 10/group) were gavaged with Water, Olive Oil (OO), or EO (0.5 mL; days 0–12) and with 0.5 mL Water or the NSAID, Indomethacin (8 mg/kg; days 5–12) daily. Disease activity index (DAI), 13C-sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. P < 0.05 was considered significant. Results. In Indomethacin-treated rats, DAI was elevated (days 10–12) and SBT values (56%) and thymus weight (55%) were decreased, relative to normal controls. Indomethacin increased duodenum (68%), colon (24%), SI (48%), caecum (48%), liver (51%) and spleen (88%) weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. Conclusions. EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin-induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy. PMID:23573127

  17. Growing up with epilepsy: A two-year investigation of cognitive development in children with new onset epilepsy

    PubMed Central

    Hermann, Bruce P.; Jones, Jana E.; Sheth, Raj; Koehn, Monica; Becker, Tara; Fine, Jason; Allen, Chase A.; Seidenberg, Michael

    2010-01-01

    Purpose To characterize patterns and determinants of normal and abnormal cognitive development in children with new onset epilepsy compared to healthy controls. Methods Longitudinal (2-year) cognitive growth was examined in 100 children, age 8-18 years, including healthy controls (n=48) and children with new onset epilepsy (n=52). Cognitive maturation was examined as a function of the presence/absence of two neurobehavioral comorbitiies (Attention Deficit Hyperactivity Disorder and/or Academic Problems) identified at the time of epilepsy diagnosis. Groups were compared across a comprehensive neuropsychological battery assessing intelligence, academic achievement, language, memory, executive function and psychomotor speed. Results Children with new onset epilepsy without neurobehavioral comorbidities were comparable to healthy controls at baseline, rate of cognitive development, and follow-up assessment across all neuropsychological domains. In contrast, the presence of neurobehavioral comorbidities were associated with significantly worse baseline and prospective cognitive trajectories across all cognitive domains, especially executive functions. Conclusion The presence of neurobehavioral comorbidities at the time of epilepsy onset is a major marker of abnormal cognitive development both prior to and after the onset of epilepsy. PMID:18785880

  18. LGI2 Truncation Causes a Remitting Focal Epilepsy in Dogs

    PubMed Central

    Seppälä, Eija H.; Jokinen, Tarja S.; Fukata, Masaki; Fukata, Yuko; Webster, Matthew T.; Karlsson, Elinor K.; Kilpinen, Sami K.; Steffen, Frank; Dietschi, Elisabeth; Leeb, Tosso; Eklund, Ranja; Zhao, Xiaochu; Rilstone, Jennifer J.; Lindblad-Toh, Kerstin; Minassian, Berge A.; Lohi, Hannes

    2011-01-01

    One quadrillion synapses are laid in the first two years of postnatal construction of the human brain, which are then pruned until age 10 to 500 trillion synapses composing the final network. Genetic epilepsies are the most common neurological diseases with onset during pruning, affecting 0.5% of 2–10-year-old children, and these epilepsies are often characterized by spontaneous remission. We previously described a remitting epilepsy in the Lagotto romagnolo canine breed. Here, we identify the gene defect and affected neurochemical pathway. We reconstructed a large Lagotto pedigree of around 34 affected animals. Using genome-wide association in 11 discordant sib-pairs from this pedigree, we mapped the disease locus to a 1.7 Mb region of homozygosity in chromosome 3 where we identified a protein-truncating mutation in the Lgi2 gene, a homologue of the human epilepsy gene LGI1. We show that LGI2, like LGI1, is neuronally secreted and acts on metalloproteinase-lacking members of the ADAM family of neuronal receptors, which function in synapse remodeling, and that LGI2 truncation, like LGI1 truncations, prevents secretion and ADAM interaction. The resulting epilepsy onsets at around seven weeks (equivalent to human two years), and remits by four months (human eight years), versus onset after age eight in the majority of human patients with LGI1 mutations. Finally, we show that Lgi2 is expressed highly in the immediate post-natal period until halfway through pruning, unlike Lgi1, which is expressed in the latter part of pruning and beyond. LGI2 acts at least in part through the same ADAM receptors as LGI1, but earlier, ensuring electrical stability (absence of epilepsy) during pruning years, preceding this same function performed by LGI1 in later years. LGI2 should be considered a candidate gene for common remitting childhood epilepsies, and LGI2-to-LGI1 transition for mechanisms of childhood epilepsy remission. PMID:21829378

  19. Behavioral Effects of Phencyclidine on Nicotine Self-Administration and Reinstatement in the Presence or Absence of a Visual Stimulus in Rats

    PubMed Central

    Swalve, Natashia; Pittenger, Steven T.; Bevins, Rick A.; Li, Ming

    2015-01-01

    Rationale Tobacco use is a serious health problem in the United States and this problem is potentiated in patients with schizophrenia. The reward system is implicated in schizophrenia and may contribute to the high comorbidity between nicotine use and schizophrenia but very little research has been done on the topic. The reward-enhancement effect of nicotine has been shown to be important in nicotine use, but there have been no studies on this effect in animal models of schizophrenia. Objectives This study was designed to determine the effects of phencyclidine, used to model negative symptoms of schizophrenia, on self-administration of nicotine with or without a co-occurring sensory reinforcer [i.e., visual stimulus (VS)] in rats. Methods Phencyclidine (2.0 mg/kg) was administered before each of 7 nicotine self-administration sessions (0.01 mg/kg/inf) after which rats (n=8–9 per group) were given 7 days of extinction without phencyclidine pretreatment. Reinstatement using phencyclidine (2.0 mg/kg), nicotine (0.2 mg/kg), and yohimbine (1.25 mg/kg, a pharmacological stressor) were tested after extinction to determine if previous exposure to phencyclidine would alter reinstatement of active lever pressing. Results Phencyclidine initially decreased nicotine self-administration, but only in the groups with a concurrent VS. This decrease in self-administration dissipated after 5 days. During reinstatement, rats that had previously received phencyclidine during self-administration with a VS were more sensitive to stress-induced reinstatement than any other group. Conclusions These results show a transitory effect of phencyclidine on nicotine self-administration. Phencyclidine may induce a potential sensitivity to pharmacological stressors contributing to reinstatement of nicotine. PMID:25845436

  20. Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model

    PubMed Central

    van Luijtelaar, Gilles; Mishra, Asht M.; Edelbroek, Peter; Coman, Daniel; Frankenmolen, Nikita; Schaapsmeerders, Pauline; Covolato, Giulio; Danielson, Nathan; Niermann, Hannah; Janeczko, Kryzstof; Kiemeneij, Anne; Burinov, Julija; Bashyal, Chhitij; Coquillette, Madeline; Lüttjohann, Annika; Hyder, Fahmeed; Blumenfeld, Hal; van Rijn, Clementina M.

    2014-01-01

    The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike–wave discharges, SWD and afterdischarges), white matter changes representing extra corticothalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2–3 or 4–5), or ethosuximide for 4 months (2–5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment. Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy. PMID:23978468

  1. Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).

    PubMed

    Rektor, Ivan; Schachter, Steven C; Arzy, Shahar; Baloyannis, Stavros J; Bazil, Carl; Brázdil, Milan; Engel, Jerome; Helmstaedter, Gerhard; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kesner, Ladislav; Komárek, Vladimír; Krämer, Günter; Leppik, Ilo E; Mann, Michael W; Mula, Marco; Risse, Gail L; Stoker, Guy W; Kasteleijn-Nolst Trenité, Dorothée G A; Trimble, Michael; Tyrliková, Ivana; Korczyn, Amos D

    2013-08-01

    Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art. PMID:23764495

  2. Clinical aspects of juvenile myoclonic epilepsy.

    PubMed

    Genton, Pierre; Thomas, Pierre; Kasteleijn-Nolst Trenité, Dorothee G A; Medina, Marco Tulio; Salas-Puig, Javier

    2013-07-01

    Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise. PMID:23756488

  3. Dreams and epilepsy.

    PubMed

    Reami, D O; Silva, D F; Albuquerque, M; Campos, C J

    1991-01-01

    The relationship between dreams and epilepsy is illustrated by two patients whose awake epileptic seizures and recurrent dreams during night sleep had similar content. In both of our cases the EEG showed right anterior temporal spike discharge, suggesting a role for the temporal lobe in the association between dreams and seizures. PMID:1985830

  4. Epilepsy and brain tumors.

    PubMed

    Englot, Dario J; Chang, Edward F; Vecht, Charles J

    2016-01-01

    Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70-80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60-75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20-50% of patients with meningioma and 20-35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60-90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

  5. Absence of long-term behavioral effects after sub-chronic administration of low doses of methamidophos in male and female rats.

    PubMed

    Temerowski, M; van der Staay, F J

    2005-01-01

    Putative long-term learning and memory effects of low-dose exposure to the cholinesterase inhibitor organophosphate methamidophos (Tamaron) early in life were studied in two parallel studies in middle-aged rats. Methamidophos was administered via the drinking water to female and male Wistar rats using nominal concentrations of 0 (control), 0.5, 1.5 and 4.5 ppm active ingredient for 16 weeks. Animals were then maintained for a recovery period of about 14 months without treatment. They were tested in the standard and repeated acquisition version of the Morris water escape task in two series of tests starting 33 and 55 weeks after termination of the methamidophos treatment. Functional observations and motor activity measurements preceded each series of testing. Exposure to methamidophos was confirmed by measurement of brain cholinesterase (ChE-B) at the end of the 16 weeks of treatment in satellite animals. At 4.5 ppm a biologically relevant reduction in ChE-B activity was observed without clinical signs of intoxication (males: 66%, females: 64% of control activity). Mid- and low-dose exposure to methamidophos revealed ChE-B activity of 90% and 100% in males and 88% and 97% in females, respectively. General examinations of the animals during treatment revealed no clinical signs suggesting cholinergic stimulation. Functional observations and motor activity measurements exhibited no relevant differences between treatment groups and controls. Neither the performance in the standard Morris water escape task that predominantly measures spatial reference memory, nor in the repeated acquisition task in the Morris tank, which predominantly measures spatial working memory, was affected by treatment with methamidophos. A small number of statistically significant differences were noted in the mean performance level between treatment groups, or between treatment by sex groups in both versions of the Morris task. However, these findings appeared to be idiosyncratic for a

  6. NMDA receptors trigger neurosecretion of 5-HT within dorsal raphé nucleus of the rat in the absence of action potential firing

    PubMed Central

    de Kock, C P J; Cornelisse, L N; Burnashev, N; Lodder, J C; Timmerman, A J; Couey, J J; Mansvelder, H D; Brussaard, A B

    2006-01-01

    Activity and calcium-dependent release of neurotransmitters from the somatodendritic compartment is an important signalling mechanism between neurones throughout the brain. NMDA receptors and vesicles filled with neurotransmitters occur in close proximity in many brain areas. It is unknown whether calcium influx through these receptors can trigger the release of somatodendritic vesicles directly, or whether postsynaptic action potential firing is necessary for release of these vesicles. Here we addressed this question by studying local release of serotonin (5-HT) from dorsal raphé nucleus (DRN) neurones. We performed capacitance measurements to monitor the secretion of vesicles in giant soma patches, in response to short depolarizations and action potential waveforms. Amperometric measurements confirmed that secreted vesicles contained 5-HT. Surprisingly, two-photon imaging of DRN neurones in slices revealed that dendritic calcium concentration changes in response to somatic firing were restricted to proximal dendritic areas. This implied that alternative calcium entry pathways may dominate the induction of vesicle secretion from distal dendrites. In line with this, transient NMDA receptor activation, in the absence of action potential firing, was sufficient to induce capacitance changes. By monitoring GABAergic transmission onto DRN 5-HT neurones in slices, we show that endogenous NMDA receptor activation, in the absence of postsynaptic firing, induced release of 5-HT, which in turn increased the frequency of GABAergic inputs through activation of 5-HT2 receptors. We propose here that calcium influx through NMDA receptors can directly induce postsynaptic 5-HT release from DRN neurones, which in turn may facilitate GABAergic input onto these cells. PMID:17053037

  7. Analysis of Genetically Complex Epilepsies

    PubMed Central

    Ottman, Ruth

    2006-01-01

    During the last decade, great progress has been made in the discovery of genes that influence risk for epilepsy. However, these gene discoveries have been in epilepsies with Mendelian modes of inheritance, which comprise only a tiny fraction of all epilepsy. Most people with epilepsy have no affected relatives, suggesting that the great majority of all epilepsies are genetically complex: multiple genes contribute to their etiology, none of which has a major effect on disease risk. Gene discovery in the genetically complex epilepsies is a formidable task. It is unclear which epilepsy phenotypes are most advantageous to study, and chromosomal localization and mutation detection are much more difficult than in Mendelian epilepsies. Association studies are very promising for the identification of complex epilepsy genes, but we are still in the earliest stages of their application in the epilepsies. Future studies should employ very large sample sizes to ensure adequate statistical power, clinical phenotyping methods of the highest quality, designs and analytic techniques that control for population stratification, and state-of-the-art molecular methods. Collaborative studies are essential to achieve these goals. PMID:16359464

  8. Absence of adverse effects of sodium metabisulphite in manufactured biscuits: results of subacute (28-days) and subchronic (85-days) feeding studies in rats.

    PubMed

    Ribera, D; Jonker, D; Narbonne, J F; O'Brien, J; Antignac, E

    2001-02-01

    Sulphites are extensively used in the food and drinks industry. Their toxicity has been previously evaluated by addition to the diet or drinking water of laboratory animals. Because interactions between sulphites and food constituents occur, the present work was conducted to determine the subacute and subchronic toxicity of sulphite-bound compounds in a finished product: manufactured biscuits. The studies were performed on Sprague Dawley, rats for 28 and 85 days of dietary exposure. Diets were prepared from sulphited or untreated (controls) biscuits with the addition of sugar, protein, vitamins and minerals according to the nutritional requirements of the animals. Groups of 10 male and 10 female rats were administered diets containing sulphited biscuits at levels of 0, 10, 35 and 75%, corresponding to 10-15, 35-45, 150-170 and 310-340 mg SO2/kg diet. In both studies, no death or clinical abnormalities were reported. Growth rate, food consumption and food conversion efficiency were not affected by treatment. No dose-related changes were observed for haematology, clinical chemistry, ocular examination, renal-function, urinalysis, organ weights or gross and microscopic examinations. The liver concentrations of vitamins A, B1, C and E were not significantly changed except for an increase in vitamin E in high-dose males after 28 days' exposure. Based on these data, the no-observed-adverse-effect level (NOAEL) of sulphites in baked biscuits was judged to be 310 mg SO2/kg diet or 25 mg/kg body weight/day. PMID:11288907

  9. Epilepsy - what to ask your doctor - child

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000222.htm Epilepsy - what to ask your doctor - child To use ... this page, please enable JavaScript. Your child has epilepsy. Children with epilepsy have seizures. A seizure is ...

  10. Genetics Home Reference: pyridoxine-dependent epilepsy

    MedlinePlus

    ... Home Health Conditions pyridoxine-dependent epilepsy pyridoxine-dependent epilepsy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Pyridoxine-dependent epilepsy is a condition that involves seizures beginning in ...

  11. Genetics Home Reference: Lafora progressive myoclonus epilepsy

    MedlinePlus

    ... Conditions Lafora progressive myoclonus epilepsy Lafora progressive myoclonus epilepsy Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures ( ...

  12. Epilepsy - what to ask your doctor - adult

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000221.htm Epilepsy - what to ask your doctor - adult To use ... on this page, please enable JavaScript. You have epilepsy. People with epilepsy have seizures. A seizure is ...

  13. Epilepsy Surgery for Pediatric Epilepsy: Optimal Timing of Surgical Intervention

    PubMed Central

    SUGANO, Hidenori; ARAI, Hajime

    2015-01-01

    Pediatric epilepsy has a wide variety of etiology and severity. A recent epidemiological study suggested that surgery might be indicated in as many as 5% of the pediatric epilepsy population. Now, we know that effective epilepsy surgery can result in seizure freedom and improvement of psychomotor development. Seizure control is the most effective way to improve patients neurologically and psychologically. In this review, we look over the recent evidence related to pediatric epilepsy surgery, and try to establish the optimal surgical timing for patients with intractable epilepsy. Appropriate surgical timing depends on the etiology and natural history of the epilepsy to be treated. The most common etiology of pediatric intractable epilepsy patients is malformation of cortical development (MCD) and early surgery is recommended for them. Patients operated on earlier than 12 months of age tended to improve their psychomotor development compared to those operated on later. Recent progress in neuroimaging and electrophysiological studies provide the possibility of very early diagnosis and comprehensive surgical management even at an age before 12 months. Epilepsy surgery is the only solution for patients with MCD or other congenital diseases associated with intractable epilepsy, therefore physicians should aim at an early and precise diagnosis and predicting the future damage, consider a surgical solution within an optimal timing. PMID:25925754

  14. CHD2 variants are a risk factor for photosensitivity in epilepsy.

    PubMed

    Galizia, Elizabeth C; Myers, Candace T; Leu, Costin; de Kovel, Carolien G F; Afrikanova, Tatiana; Cordero-Maldonado, Maria Lorena; Martins, Teresa G; Jacmin, Maxime; Drury, Suzanne; Krishna Chinthapalli, V; Muhle, Hiltrud; Pendziwiat, Manuela; Sander, Thomas; Ruppert, Ann-Kathrin; Møller, Rikke S; Thiele, Holger; Krause, Roland; Schubert, Julian; Lehesjoki, Anna-Elina; Nürnberg, Peter; Lerche, Holger; Palotie, Aarno; Coppola, Antonietta; Striano, Salvatore; Gaudio, Luigi Del; Boustred, Christopher; Schneider, Amy L; Lench, Nicholas; Jocic-Jakubi, Bosanka; Covanis, Athanasios; Capovilla, Giuseppe; Veggiotti, Pierangelo; Piccioli, Marta; Parisi, Pasquale; Cantonetti, Laura; Sadleir, Lynette G; Mullen, Saul A; Berkovic, Samuel F; Stephani, Ulrich; Helbig, Ingo; Crawford, Alexander D; Esguerra, Camila V; Kasteleijn-Nolst Trenité, Dorothee G A; Koeleman, Bobby P C; Mefford, Heather C; Scheffer, Ingrid E; Sisodiya, Sanjay M

    2015-05-01

    Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2.17 × 10(-5)). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3.50 × 10(-4)). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into

  15. CHD2 variants are a risk factor for photosensitivity in epilepsy

    PubMed Central

    Myers, Candace T.; Leu, Costin; de Kovel, Carolien G. F.; Afrikanova, Tatiana; Cordero-Maldonado, Maria Lorena; Martins, Teresa G.; Jacmin, Maxime; Drury, Suzanne; Krishna Chinthapalli, V.; Muhle, Hiltrud; Pendziwiat, Manuela; Sander, Thomas; Ruppert, Ann-Kathrin; Møller, Rikke S.; Thiele, Holger; Krause, Roland; Schubert, Julian; Lehesjoki, Anna-Elina; Nürnberg, Peter; Lerche, Holger; Palotie, Aarno; Coppola, Antonietta; Striano, Salvatore; Gaudio, Luigi Del; Boustred, Christopher; Schneider, Amy L.; Lench, Nicholas; Jocic-Jakubi, Bosanka; Covanis, Athanasios; Capovilla, Giuseppe; Veggiotti, Pierangelo; Piccioli, Marta; Parisi, Pasquale; Cantonetti, Laura; Sadleir, Lynette G.; Mullen, Saul A.; Berkovic, Samuel F.; Stephani, Ulrich; Helbig, Ingo; Crawford, Alexander D.; Esguerra, Camila V.; Kasteleijn-Nolst Trenité, Dorothee G. A.

    2015-01-01

    Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2·17 × 10−5). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3·50 × 10−4). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research

  16. Epilepsy associated tumors: Review article

    PubMed Central

    Giulioni, Marco; Marucci, Gianluca; Martinoni, Matteo; Marliani, Anna Federica; Toni, Francesco; Bartiromo, Fiorina; Volpi, Lilia; Riguzzi, Patrizia; Bisulli, Francesca; Naldi, Ilaria; Michelucci, Roberto; Baruzzi, Agostino; Tinuper, Paolo; Rubboli, Guido

    2014-01-01

    Long-term epilepsy associated tumors (LEAT) represent a well known cause of focal epilepsies. Glioneuronal tumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly arising in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic network with complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation. PMID:25405186

  17. Epilepsy in the developing world.

    PubMed

    Carpio, Arturo; Hauser, W Allen

    2009-07-01

    Developing countries (DCs) and developed countries have geographic, economic, and social differences. The prevalence and incidence of epilepsy are higher in DCs than in developed countries. However, within DCs, given the high incidence of epilepsy, the prevalence is relatively low, which may be due to high mortality for people with epilepsy (PWE). Neurocysticercosis is one of the main causes of symptomatic epilepsy in many DCs. Prognosis in DCs seems similar to that in developed countries. Because phenobarbital and phenytoin are available and inexpensive, they are the drugs most often used in DCs. The cost of newer antiepileptic drugs and the limited availability of resources for epilepsy care in DCs mean that care for PWE in DCs is marginalized and that many people receive no pharmacologic treatment. The most cost-effective way to decrease the treatment gap in DCs would be to deliver the epilepsy services through primary health care. PMID:19515285

  18. Confronting the stigma of epilepsy.

    PubMed

    Thomas, Sanjeev V; Nair, Aparna

    2011-07-01

    Stigma and resultant psychosocial issues are major hurdles that people with epilepsy confront in their daily life. People with epilepsy, particularly women, living in economically weak countries are often ill equipped to handle the stigma that they experience at multiple levels. This paper offers a systematic review of the research on stigma from sociology and social psychology and details how stigma linked to epilepsy or similar conditions can result in stereotyping, prejudice and discrimination. We also briefly discuss the strategies that are most commonly utilized to mitigate stigma. Neurologists and other health care providers, social workers, support groups and policy makers working with epilepsy need to have a deep understanding of the social and cultural perceptions of epilepsy and the related stigma. It is necessary that societies establish unique determinants of stigma and set up appropriate strategies to mitigate stigma and facilitate the complete inclusion of people with epilepsy as well as mitigating any existing discrimination. PMID:22028525

  19. Confronting the stigma of epilepsy

    PubMed Central

    Thomas, Sanjeev V.; Nair, Aparna

    2011-01-01

    Stigma and resultant psychosocial issues are major hurdles that people with epilepsy confront in their daily life. People with epilepsy, particularly women, living in economically weak countries are often ill equipped to handle the stigma that they experience at multiple levels. This paper offers a systematic review of the research on stigma from sociology and social psychology and details how stigma linked to epilepsy or similar conditions can result in stereotyping, prejudice and discrimination. We also briefly discuss the strategies that are most commonly utilized to mitigate stigma. Neurologists and other health care providers, social workers, support groups and policy makers working with epilepsy need to have a deep understanding of the social and cultural perceptions of epilepsy and the related stigma. It is necessary that societies establish unique determinants of stigma and set up appropriate strategies to mitigate stigma and facilitate the complete inclusion of people with epilepsy as well as mitigating any existing discrimination. PMID:22028525

  20. Epilepsy associated tumors: Review article.

    PubMed

    Giulioni, Marco; Marucci, Gianluca; Martinoni, Matteo; Marliani, Anna Federica; Toni, Francesco; Bartiromo, Fiorina; Volpi, Lilia; Riguzzi, Patrizia; Bisulli, Francesca; Naldi, Ilaria; Michelucci, Roberto; Baruzzi, Agostino; Tinuper, Paolo; Rubboli, Guido

    2014-11-16

    Long-term epilepsy associated tumors (LEAT) represent a well known cause of focal epilepsies. Glioneuronal tumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly arising in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic network with complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation. PMID:25405186

  1. [Progress in molecular genetics of epilepsy].

    PubMed

    Tang, Beisha; Zhang, Yuhu

    2002-12-01

    Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function. PMID:12476426

  2. Spontaneous Periodontitis Development in Diabetic Rats Involves an Unrestricted Expression of Inflammatory Cytokines and Tissue Destructive Factors in the Absence of Major Changes in Commensal Oral Microbiota

    PubMed Central

    Claudino, Marcela; Gennaro, Gabriela; Cestari, Tania Mary; Spadella, César Tadeu; Garlet, Gustavo Pompermaier; Assis, Gerson Francisco

    2012-01-01

    Diabetes mellitus is a heterogeneous group of disorders, in which hyperglycemia is a main feature. The objective was to evaluate the involvement of RAGE, inflammatory cytokines, and metalloproteinases in spontaneous periodontitis triggered by diabetes induction. Immunohistochemical procedures for MMP-2, MMP-9, TNF-α, IL-1β, IL-6, RANKL, and RAGE were performed in rats after 1, 3, 6, 9, and 12 months of diabetes induction. Total DNA was extracted from paraffin-embedded tissues and evaluated by Real-TimePCR for 16S total bacterial load and specific periodontopathogens. Our data did not demonstrate differences in microbiological patterns between groups. In diabetic groups, an increase in RAGE-positive cells was detected at 6, 9, and 12 months, while TNF-alpha-stained cells were more prevalent at 6 and 12 months. In experimental groups, IL-β-positive cells were increased after 12 months, IL-6 stained cells were increased at 9 and 12 months, and RANKL-positive cells at 9 months. Diabetes resulted in widespread expression of RAGE, followed by expression of proinflammatory mediators, without major alterations in oral microbial profile. The pervasive expression of cytokines suggests that spontaneous periodontitis development may be independent of microbial stimulation and may be triggered by diabetes-driven imbalance of homeostasis. PMID:22611374

  3. Neuropathology of Temporal Lobe Epilepsy

    PubMed Central

    Al Sufiani, Fahd; Ang, Lee Cyn

    2012-01-01

    Pathologic findings in surgical resections from patients with temporal lobe epilepsy include a wide range of diagnostic possibilities that can be categorized into different groups on the basis of etiology. This paper outlines the various pathologic entities described in temporal lobe epilepsy, including some newly recognized epilepsy-associated tumors, and briefly touch on the recent classification of focal cortical dysplasia. This classification takes into account coexistent pathologic lesions in focal cortical dysplasia. PMID:22957233

  4. [Dietary therapy of epilepsy].

    PubMed

    Imai, Katsumi; Ishihara, Eiko; Ikeda, Hiroko

    2014-05-01

    Reappraisal of ketogenic diets (KD) were delayed in Japan compared to USA and Korea. The reasons are unknown, but possible explanations are (1) Japanese food culture prefers rice and less fat and (2) ACTH therapy is preferred for West syndrome in Japan. Since Japanese child neurologists were surprised at dramatic effects on glucose transporter 1 deficiency syndrome (Glut-1DS) in 2003, KD have been slowly accepted for treatment of epilepsy in Japan. New generation KD including modified Atkins diet (mAD) are preferred to classical KD. KD can be causal therapy in Glut-1DS and some of mitochondrial disorders, though anti-epileptic drugs are symptomatic therapy. KD can alleviate intractable seizures in epilepsies with brain malformation in addition to West syndrome and Dravet syndrome, etc. KD may work for brain tumor, cancer, neurodegenerative disorders including Alzheimer's disease. C7-8 triglycerides or fatty acid esters are under development as medicines replacing KD. PMID:24912289

  5. Burns and epilepsy.

    PubMed

    Berrocal, M

    1997-01-01

    This is a report of the first descriptive analytic study of a group of 183 burn patients, treated in the Burn Unit at the University Hospital of Cartagena, Colombia during the period since January 1985 until December 1990. There is presented experience with the selected group of 24 patients in whom the diagnosis of burn was associated with epilepsy. There is also analysed and described the gravity of the scars sequels, neurological disorders, the complication of the burn and an impact of this problem on the patient, his (her) family and the community. It is very important to report that there was found Neurocisticercosis in 66.6% of the group of burn patients with epilepsy, and it is probably the first risk factor of burn in this group. PMID:9212488

  6. Inflammation and Epilepsy

    PubMed Central

    Vezzani, Annamaria

    2005-01-01

    In recent years, increasing evidence has indicated that immune and inflammatory reactions occur in brain in various central nervous system (CNS) diseases. Furthermore, inflammatory processes, such as the production of proinflammatory cytokines and related molecules, have been described in brain after seizures induced in experimental models and in clinical cases of epilepsy. Although little is known about the role of inflammation in epilepsy, it has been hypothesized that activation of the innate immune system and associated inflammatory reactions in brain may mediate some of the molecular and structural changes occurring during and after seizure activity. Whether the innate immune response that takes place in epileptic tissue is beneficial or noxious to the CNS is still an open and intriguing question that should be addressed by further investigations. PMID:16059445

  7. Childhood epilepsy in Ilorin, Nigeria.

    PubMed

    Ojuawo, A; Joiner, K T

    1997-02-01

    Ninety eight children with epilepsy attending the Neurology clinic, University of Ilorin Teaching Hospital over a two year period were studied prospectively. Males were more affected than females in a ratio of 5:3. Generalised tonic-clonic seizures accounted for 62.2% of the cases, and partial seizures for 17.4%. Infantile spasms were seen exclusively in infants less than two years old and absence and generalised seizures in children more than three years of age. Skull radiography showed abnormal findings in 11.2%. Ectroencephalography showed typical findings in 43.9%. Hemiplegia was the most common neurological sequelae (30.3%). Other sequelae include hyperactivity, irrational behaviour, expressive aphasia, mental subnormality, deafness, and blindness in that order. Therapy with a single appropriate anticonvulsant was usually effective for seizure control except in some patients with focal seizures, infantile spasms, severely delayed developmental milestones and prolonged seizures. Poor drug compliance remains the major constraint to adequate seizure control, further compounded in this environment by nonavailability of drugs and unaffordable costs. PMID:9185388

  8. Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy.

    PubMed

    Sivakumar, Siddharth S; Namath, Amalia G; Tuxhorn, Ingrid E; Lewis, Stephen J; Galán, Roberto F

    2016-04-01

    We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy. PMID:26888110

  9. Lennox-Gastaut syndrome and epilepsy with myoclonic-astatic seizures.

    PubMed

    Kaminska, Anna; Oguni, Hirokazu

    2013-01-01

    Among nonsymptomatic epilepsies exhibiting several types of generalized seizures in children two syndromes were progressively identified: epilepsy with myoclonic-astatic seizures (MAE) and nonsymptomatic Lennox-Gastaut syndrome (LGS). Various approaches based on etiology, electroclinical semiology, and mathematical analysis have progressively helped to distinguish these two conditions. Both conditions preferentially affect boys. The course is stereotyped in MAE, characterized by progressive worsening of epilepsy, usual pharmacoresistance at onset and tonic-clonic seizures, myoclonus and frequent episodes of myoclonic status epilepticus. EEG shows 3Hz spike wave bursts characteristic of idiopathic generalized epilepsy together with slowing of the tracing. In LGS, major seizures are mainly atypical absences and tonic seizures with 0.5-2Hz slow spike-waves and eventually focal anomalies. Prognosis in both syndromes ranges from recovery without sequelae to pharmacoresistant epilepsy that has improved over the past 2 decades with the new generation antiepileptic compounds. Iatrogenic factors may contribute to the poor prognosis, mainly in MAE. Pathophysiology remains speculative for both syndromes: although both share factors of brain maturation, MAE is probably mainly related to genetic predisposition whereas LGS results from some unidentified cortical brain malformation. In unfavorable cases, there may therefore be a continuum between both syndromes. They need to be distinguished from other epilepsy syndromes and inborn errors of metabolism that begin in the same age range: atypical idiopathic benign epilepsy, frontal lobe epilepsy with secondary bisynchrony, ring chromosome 20, ceroid lipofuscinosis, and nonsymptomatic late-onset spasms. PMID:23622212

  10. Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy

    PubMed Central

    Reddy, Doodipala Samba

    2016-01-01

    Catamenial epilepsy is a type of refractory epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of catamenial epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual catamenial epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of catamenial epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of catamenial epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for catamenial epilepsy. PMID:27147973

  11. Potassium Channels in Epilepsy.

    PubMed

    Köhling, Rüdiger; Wolfart, Jakob

    2016-01-01

    This review attempts to give a concise and up-to-date overview on the role of potassium channels in epilepsies. Their role can be defined from a genetic perspective, focusing on variants and de novo mutations identified in genetic studies or animal models with targeted, specific mutations in genes coding for a member of the large potassium channel family. In these genetic studies, a demonstrated functional link to hyperexcitability often remains elusive. However, their role can also be defined from a functional perspective, based on dynamic, aggravating, or adaptive transcriptional and posttranslational alterations. In these cases, it often remains elusive whether the alteration is causal or merely incidental. With ∼80 potassium channel types, of which ∼10% are known to be associated with epilepsies (in humans) or a seizure phenotype (in animals), if genetically mutated, a comprehensive review is a challenging endeavor. This goal may seem all the more ambitious once the data on posttranslational alterations, found both in human tissue from epilepsy patients and in chronic or acute animal models, are included. We therefore summarize the literature, and expand only on key findings, particularly regarding functional alterations found in patient brain tissue and chronic animal models. PMID:27141079

  12. Progressive myoclonic epilepsies

    PubMed Central

    Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico

    2014-01-01

    Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized. PMID:24384641

  13. Nonpharmacological treatment of epilepsy.

    PubMed

    Saxena, V S; Nadkarni, V V

    2011-07-01

    Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG) biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine). Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70-80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment. PMID:22028523

  14. Purinergic signaling in epilepsy.

    PubMed

    Rassendren, François; Audinat, Etienne

    2016-09-01

    Until recently, analysis of the mechanisms underlying epilepsy was centered on neuron dysfunctions. Accordingly, most of the available pharmacological treatments aim at reducing neuronal excitation or at potentiating neuronal inhibition. These therapeutic options can lead to obvious secondary effects, and, moreover, seizures cannot be controlled by any known medication in one-third of the patients. A purely neurocentric view of brain functions and dysfunctions has been seriously questioned during the past 2 decades because of the accumulation of experimental data showing the functional importance of reciprocal interactions between glial cells and neurons. In the case of epilepsy, our current knowledge of the human disease and analysis of animal models clearly favor the involvement of astrocytes and microglial cells during the progression of the disease, including at very early stages, opening the way to the identification of new therapeutic targets. Purinergic signaling is a fundamental feature of neuron-glia interactions, and increasing evidence indicates that modifications of this pathway contribute to the functional remodeling of the epileptic brain. This Review discusses the recent experimental results indicating the roles of astrocytic and microglial P2X and P2Y receptors in epilepsy. © 2016 Wiley Periodicals, Inc. PMID:27302739

  15. Nonpharmacological treatment of epilepsy

    PubMed Central

    Saxena, V. S.; Nadkarni, V. V.

    2011-01-01

    Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG) biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine). Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70–80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment. PMID:22028523

  16. [Genetics of idiopathic epilepsies].

    PubMed

    Weber, Y G; Lerche, H

    2013-02-01

    Idiopathic epilepsies are genetically determined. They are characterized by the observed seizure types, an age-dependent onset, electroencephalographic criteria and concomitant symptoms, such as movement disorders or developmental delay. The main subtypes are the idiopathic (i) generalized, (ii) the focal epilepsies including the benign syndromes of early childhood and (iii) the epileptic encephalopathies as well as the fever-associated syndromes. In recent years, an increasing number of mutations have been identified in genes encoding ion channels, proteins associated to the vesical synaptic cycle or proteins involved in energy metabolism. These mechanisms are pathophysiologically plausible as they influence neuronal excitability. The large number of genetic defects in epilepsy complicates the genetic diagnostic analysis but novel genetic methods are available covering all known genes at a reasonable price. The proof of a genetic defect leads to a definitive diagnosis, is important for the prognostic and genetic counselling and may influence therapeutic decisions in some cases, so that genetic diagnostic testing is becoming increasingly more important and meaningful in many cases in daily clinical practice. PMID:23392265

  17. The epilepsy of Dostoevsky.

    PubMed

    Kiloh, L G

    1986-01-01

    The evidence in favour of a diagnosis of limbic epilepsy in the case of Dostoevsky is reviewed. Independent records from numerous biographical sources support the widely held view that Dostoevsky had frequent convulsive episodes, that the episodes began in childhood and continued throughout his life and that Dostoevsky himself was able accurately to record the premonitory aura and sequelae of such episodes. In addition the increasing memory impairment he suffered both for recent and remote events from the age of 40 supports the presence of progressive brain damage. This information renders implausible the analytic interpretations of Freud and his followers, that Dostoevsky's epilepsy was hysterical in origin, where epileptiform somatization was presumed to dispose of excessive psychic excitation, and that this process had its roots in Dostoevsky's unconscious hatred of his father and latent homosexuality. Nevertheless, Dostoevsky's neuroticism is clearly supported by his life-long hypochondriasis, obsessionality, paranoid traits, tendency to reactive depressions, and experience of quasi-hallucinatory episodes which were probably not epileptic in origin. Neither his epilepsy nor his neuroticism can explain or detract from the profundity and wisdom of the literary monuments which clearly attest Dostoevsky's ample genius. PMID:3085083

  18. Understanding of Epilepsy by Children and Young People with Epilepsy

    ERIC Educational Resources Information Center

    Lewis, Ann; Parsons, Sarah

    2008-01-01

    There is a striking dearth of studies focusing sensitively and in depth on the mainstream educational experiences of children with epilepsy, as viewed by those children themselves. The one-year project (2006-7) reported here addresses that gap. Children's perceptions about mainstream teachers' understanding of epilepsy and school-based needs are…

  19. Regionally specific expression of high-voltage-activated calcium channels in thalamic nuclei of epileptic and non-epileptic rats.

    PubMed

    Kanyshkova, Tatyana; Ehling, Petra; Cerina, Manuela; Meuth, Patrick; Zobeiri, Mehrnoush; Meuth, Sven G; Pape, Hans-Christian; Budde, Thomas

    2014-07-01

    The polygenic origin of generalized absence epilepsy results in dysfunction of ion channels that allows the switch from physiological asynchronous to pathophysiological highly synchronous network activity. Evidence from rat and mouse models of absence epilepsy indicates that altered Ca(2+) channel activity contributes to cellular and network alterations that lead to seizure activity. Under physiological circumstances, high voltage-activated (HVA) Ca(2+) channels are important in determining the thalamic firing profile. Here, we investigated a possible contribution of HVA channels to the epileptic phenotype using a rodent genetic model of absence epilepsy. In this study, HVA Ca(2+) currents were recorded from neurons of three different thalamic nuclei that are involved in both sensory signal transmission and rhythmic-synchronized activity during epileptic spike-and-wave discharges (SWD), namely the dorsal part of the lateral geniculate nucleus (dLGN), the ventrobasal thalamic complex (VB) and the reticular thalamic nucleus (NRT) of epileptic Wistar Albino Glaxo rats from Rijswijk (WAG/Rij) and non-epileptic August Copenhagen Irish (ACI) rats. HVA Ca(2+) current densities in dLGN neurons were significantly increased in epileptic rats compared with non-epileptic controls while other thalamic regions revealed no differences between the strains. Application of specific channel blockers revealed that the increased current was carried by L-type Ca(2+) channels. Electrophysiological evidence of increased L-type current correlated with up-regulated mRNA and protein expression of a particular L-type channel, namely Cav1.3, in dLGN of epileptic rats. No significant changes were found for other HVA Ca(2+) channels. Moreover, pharmacological inactivation of L-type Ca(2+) channels results in altered firing profiles of thalamocortical relay (TC) neurons from non-epileptic rather than from epileptic rats. While HVA Ca(2+) channels influence tonic and burst firing in ACI and WAG

  20. The Music Student with Epilepsy

    ERIC Educational Resources Information Center

    Murdock, Matthew C.; Morgan, Joseph A.; Laverghetta, Thomas S.

    2012-01-01

    The teacher-student relationship can afford the music educator an opportunity to be the first to identify behaviors associated with epilepsy. A case of a student with epilepsy, based on the authors' experience, is described in which the music educators were the first and only individuals to become aware of a change in the student's behavior, after…

  1. Hippocampal Hyperexcitability is Modulated by Microtubule-Active Agent: Evidence from In Vivo and In Vitro Epilepsy Models in the Rat

    PubMed Central

    Carletti, Fabio; Sardo, Pierangelo; Gambino, Giuditta; Liu, Xin-An; Ferraro, Giuseppe; Rizzo, Valerio

    2016-01-01

    The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological models of epileptiform activity in the rat hippocampus. To this aim, we used in vivo maximal dentate activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to assess the effects of nocodazole (NOC) and paclitaxel (PAC), that respectively destabilize and stabilize microtubule structures. In particular, in the MDA paroxysmal discharge is electrically induced, whereas the HEBA is obtained by altering extracellular ionic concentrations. Our results provided evidence that NOC 10 μM was able to reduce the severity of MDA seizures, without inducing neurotoxicity as verified by the immunohistochemical assay. In some cases, paroxysmal discharge was completely blocked during the maximal effect of the drug. These data were also in agreement with the outcomes of in vitro HEBA, since NOC markedly decreased burst activity that was even silenced occasionally. In contrast, PAC at 10 μM did not exert a clear action in both paradigms. The present study, targeting cellular mechanisms not much considered so far, suggests the possibility that microtubule-active drugs could modulate brain hyperexcitability. This contributes to the hypothesis that cytoskeleton function may affect synaptic processes, relapsing on bioelectric aspects of epileptic activity. PMID:26903814

  2. Hippocampal Hyperexcitability is Modulated by Microtubule-Active Agent: Evidence from In Vivo and In Vitro Epilepsy Models in the Rat.

    PubMed

    Carletti, Fabio; Sardo, Pierangelo; Gambino, Giuditta; Liu, Xin-An; Ferraro, Giuseppe; Rizzo, Valerio

    2016-01-01

    The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological models of epileptiform activity in the rat hippocampus. To this aim, we used in vivo maximal dentate activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to assess the effects of nocodazole (NOC) and paclitaxel (PAC), that respectively destabilize and stabilize microtubule structures. In particular, in the MDA paroxysmal discharge is electrically induced, whereas the HEBA is obtained by altering extracellular ionic concentrations. Our results provided evidence that NOC 10 μM was able to reduce the severity of MDA seizures, without inducing neurotoxicity as verified by the immunohistochemical assay. In some cases, paroxysmal discharge was completely blocked during the maximal effect of the drug. These data were also in agreement with the outcomes of in vitro HEBA, since NOC markedly decreased burst activity that was even silenced occasionally. In contrast, PAC at 10 μM did not exert a clear action in both paradigms. The present study, targeting cellular mechanisms not much considered so far, suggests the possibility that microtubule-active drugs could modulate brain hyperexcitability. This contributes to the hypothesis that cytoskeleton function may affect synaptic processes, relapsing on bioelectric aspects of epileptic activity. PMID:26903814

  3. Auras in generalized epilepsy

    PubMed Central

    Carlson, Chad; Bluvstein, Judith; Chong, Derek J.; Friedman, Daniel; Kirsch, Heidi E.

    2014-01-01

    Objective: We studied the frequency of auras in generalized epilepsy (GE) using a detailed semistructured diagnostic interview. Methods: In this cross-sectional study, participants with GE were drawn from the Epilepsy Phenome/Genome Project (EPGP). Responses to the standardized diagnostic interview regarding tonic-clonic (grand mal) seizures were then examined. This questionnaire initially required participants to provide their own description of any subjective phenomena before their “grand mal seizures.” Participants who provided answers to these questions were considered to have an aura. All participants were then systematically queried regarding a list of specific symptoms occurring before grand mal seizures, using structured (closed-ended) questions. Results: Seven hundred ninety-eight participants with GE were identified, of whom 530 reported grand mal seizures. Of these, 112 (21.3%) reported auras in response to the open-ended question. Analysis of responses to the closed-ended questions suggested that 341 participants (64.3%) experienced at least one form of aura. Conclusions: Auras typically associated with focal epilepsy were reported by a substantial proportion of EPGP subjects with GE. This finding may support existing theories of cortical and subcortical generators of GE with variable spread patterns. Differences between responses to the open-ended question and closed-ended questions may also reflect clinically relevant variation in patient responses to history-taking and surveys. Open-ended questions may underestimate the prevalence of specific types of auras and may be in part responsible for the underrecognition of auras in GE. In addition, structured questions may influence participants, possibly leading to a greater representation of symptoms. PMID:25230998

  4. Unnecessary polypharmacy for epilepsy.

    PubMed Central

    Shorvon, S D; Reynolds, E H

    1977-01-01

    A retrospective survey of 50 adult epileptic outpatients who were taking two anticonvulsants drugs showed that seizure control had improved in the six months after the introduction of the second drug in only 36%. When blood concentrations of the two anticonvulsants were subsequently measured improvement in seizure control was found to be significantly related to the presence of optimum blood concentrations of at least one drug. Much unnecessary polypharmacy in the treatment of epilepsy could be avoided by ensuring an optimum blood concentration of one drug before considering the addition of a second. PMID:406001

  5. Molecular mechanisms of epilepsy

    PubMed Central

    Staley, Kevin

    2015-01-01

    Decades of experimental work have established an imbalance of excitation and inhibition as the leading mechanism of the transition from normal brain function to seizure. In epilepsy, these transitions are rare and abrupt. Transition processes incorporating positive feedback, such as activity-dependent disinhibition, could provide these unique timing features. A rapidly expanding array of genetic etiologies will help delineate the molecular mechanism(s). This delineation will entail quite a bit of cell biology. The genes discovered to date are currently more remarkable for their diversity than their similarities. PMID:25710839

  6. Mapping preictal networks preceding childhood absence seizures using magnetoencephalography.

    PubMed

    Jacobs-Brichford, Eliza; Horn, Paul S; Tenney, Jeffrey R

    2014-10-01

    The electrographic hallmark of childhood absence seizures is 3 Hz generalized spike and wave discharges; however, there is likely a focal thalamic or cortical onset that cannot be detected using scalp electroencephalography (EEG). The purpose of this study was to study the earliest preictal changes in children with absence epilepsy. In this report, magnetoencephalography recordings of 44 absence seizures recorded from 12 children with drug-naïve childhood absence seizures were used to perform time frequency analysis and source localization prior to the onset of the seizures. Evidence of preictal magnetoencephalography frequency changes were detected a mean of 694 ms before the initial spike on the EEG. A consistent pattern of focal sources was present in the frontal cortex and thalamus during this preictal period, but source localization occurred synchronously so that independent activity between the 2 structures could not be distinguished. PMID:24532809

  7. Psychiatric comorbidities among patients with epilepsy in Montenegro.

    PubMed

    Vujisić, Slavica; Vodopić, Sanja; Radulović, Ljiljana; Injac-Stevović, Lidija

    2014-12-01

    The aim of this study was to evaluate the prevalence of psychiatric comorbidities, depression and anxiety, among patients with epilepsy in the outpatient Clinic for Epilepsy, Clinical Centre of Montenegro. Patients aged 18 and above with a diagnosis of epilepsy for at least one year were consecutively enrolled during a six-month period. Patients anonymously filled out a questionnaire which included data on the gender, age, education, marital status and degree of seizure control. The Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A) were used to evaluate the presence or absence of anxiety and depression. Total number of study patients was 70, including 52 patients with partial seizures and 18 patients with generalized tonic-clonic seizures. The mean patient age was 37 ± 7.92 years. The prevalence of depression in our sample was 32.8%, whereas the prevalence of anxiety was 21.4%. Patients with partial seizures were more depressed, while those with idiopathic generalized seizures were more anxious (p < 0.01). Depression was associated with a lower educational level, unemployment and poor seizure control (p < 0.05). The number of antiepileptic drugs showed a trend towards negative association with depression (p = 0.005). Anxiety was associated with the level of education and uncontrolled seizures (p < 0.01). Neither depression nor anxiety was associated with age, gender, marital status, age at onset and duration of epilepsy. Psychiatric disorders among patients with epilepsy are quite common but yet under-recognized. Therefore, appropriate recognition and efficient treatment of these disorders in patients with epilepsy might improve their quality of life and could consequently lead to better treatment success. PMID:25868308

  8. Segregation analysis of juvenile myoclonic epilepsy

    SciTech Connect

    Weissbecker, K.A.; Delgado-Escueta, A.V.; Medina, M.T.

    1994-09-01

    Juvenile myoclonic epilepsy (JME) is a non-progressive epilepsy characterized by involuntary jerks and an adolescent age of onset. There conflicting reports regarding the mode of inheritance of JME - polygenic, autosomal recessive, and two-locus models have all been proposed. We performed a segregation analysis of 53 nuclear families of JME probands using the Elston and Stewart algorithm (S.A.G.E version 2.1). Relatives of the proband were classified as affected if they had a confirmed history of JME, absence or grand mal epilepsy, or if they were clinically asymptomatic but had 3.5-6 Hz multispike wave complexes on electroencephalography. Using these criteria, 40 relatives were affected in addition to the 53 probands. All Mendelian models were rejected when compared to the unrestricted model which estimated transmission probabilities. The environmental models were also rejected. Of the Mendelian modes, the most parsimonious model was the autosomal recessive model with 53% penetrance and a rate of sporadic cases of 0.0039. We conclude that although there is evidence for a genetic component contributing to the familiality of JME, this component can not be explained by a single major gene. These results, along with contradictory reports regarding the linkage of JME to the short arm of chromosome 6, suggest the presence of genetic heterogeneity and/or a more complex mode of inheritance, such as a two-locus model. Since lod score linkage analyses are dependent on the assumption of a single major gene mode, these findings emphasize the necessity of performing non-parametric linkage analyses when studying JME.

  9. Recognizing and preventing epilepsy-related mortality

    PubMed Central

    Spruill, Tanya; Thurman, David; Friedman, Daniel

    2016-01-01

    Epilepsy is associated with a high rate of premature mortality from direct and indirect effects of seizures, epilepsy, and antiseizure therapies. Sudden unexpected death in epilepsy (SUDEP) is the second leading neurologic cause of total lost potential life-years after stroke, yet SUDEP may account for less than half of all epilepsy-related deaths. Some epilepsy groups are especially vulnerable: individuals from low socioeconomic status groups and those with comorbid psychiatric illness die more often than controls. Despite clear evidence of an important public health problem, efforts to assess and prevent epilepsy-related deaths remain inadequate. We discuss factors contributing to the underestimation of SUDEP and other epilepsy-related causes of death. We suggest the need for a systematic classification of deaths directly due to epilepsy (e.g., SUDEP, drowning), due to acute symptomatic seizures, and indirectly due to epilepsy (e.g., suicide, chronic effects of antiseizure medications). Accurately estimating the frequency of epilepsy-related mortality is essential to support the development and assessment of preventive interventions. We propose that educational interventions and public health campaigns targeting medication adherence, psychiatric comorbidity, and other modifiable risk factors may reduce epilepsy-related mortality. Educational campaigns regarding sudden infant death syndrome and fires, which kill far fewer Americans than epilepsy, have been widely implemented. We have done too little to prevent epilepsy-related deaths. Everyone with epilepsy and everyone who treats people with epilepsy need to know that controlling seizures will save lives. PMID:26674330

  10. Priorities in pediatric epilepsy research

    PubMed Central

    Baca, Christine B.; Loddenkemper, Tobias; Vickrey, Barbara G.; Dlugos, Dennis

    2013-01-01

    The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of patient-centered and patient-driven mandates for developing best practices in care, particularly for epilepsy beginning under age 3 years. The workshop brought together parents, representatives of voluntary advocacy organizations, physicians, allied health professionals, researchers, and administrators to identify priority areas for pediatric epilepsy care and research including implementation and testing of interventions designed to improve care processes and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure control but also behavioral, academic, and social functioning; 2) early and accurate diagnosis and optimal treatment; 3) role and involvement of parents (communication and shared decision-making); and 4) integration of school and community organizations with epilepsy care delivery. Key factors influencing pediatric epilepsy care included the child's impairments and seizure presentation, parents, providers, the health care system, and community systems. Care was represented as a sequential process from initial onset of seizures to referral for comprehensive evaluation when needed. We considered an alternative model in which comprehensive care would be utilized from onset, proactively, rather than reactively after pharmacoresistance became obvious. Barriers, including limited levels of evidence about many aspects of diagnosis and management, access to care—particularly epilepsy specialty and behavioral health care—and implementation, were identified. Progress hinges on coordinated research efforts that systematically address gaps in knowledge and overcoming barriers to access and implementation. The stakes are considerable, and the potential benefits for reduced burden of refractory epilepsy and lifelong disabilities may be enormous. PMID:23966254

  11. The office management of epilepsy.

    PubMed

    Camfield, Peter; Camfield, Carol

    2006-12-01

    Epilepsy in children is mostly diagnosed and treated in an ambulatory office setting. This article reviews the literature and offers opinions about the best practice from the time of diagnosis through to remission and beyond. The diagnosis and assignment of an epilepsy syndrome may be difficult, and even experts disagree in many cases. Regular review of the basic diagnosis and semiology of seizures is suggested throughout treatment. Workup should always include an electroencephalogram and usually magnetic resonance imaging. Antiepileptic drugs (AEDs) suppress seizures but appear to have little effect on long-term remission, and the choice of AED is for the most part arbitrary with most AEDs having a similar success rate when used as the first drug. Families have a great need for accurate information, and their ability to cope with the unpredictable nature of seizures may be assisted by "rescue" home benzodiazepines. Surveillance for drug toxicity and side effects is a critical clinical skill that is not assisted by routine blood tests or AED serum levels. Most children with epilepsy do not have many seizures and need not have significant restrictions on their activities. In the long run, comorbidities (especially learning and behavior problems) have a greater impact on social function than the epilepsy. Management of these problems may extend well beyond remission of the epilepsy. The child neurologist needs to prepare children with persistent epilepsy for transfer to adult epilepsy services. PMID:17178350

  12. Genetic Causes of Generalized Epilepsies.

    PubMed

    Helbig, Ingo

    2015-06-01

    Generalized epilepsies, particularly the idiopathic or genetic generalized epilepsies (GGEs), represent some of the most common epilepsies. Clinical genetic data including family studies and twin studies provide compelling evidence for a prominent genetic impact. The first decade of the 21st century was marked by progress in understanding the basic biology of generalized epilepsies including generalized/genetic epilepsies with febrile seizures plus (GEFS+) and GGE through studies of large families, discovering causative mutations in SCN1A, SCN1B, GABRG2, and GABRA1. Subsequently, recurrent microdeletions at 15q13.3, 16p13.11, and 15q11.2 were found to be relevant risk factors for nonfamilial GGE. Genes for epileptic encephalopathies such as SLC2A1 were rediscovered in GGE, highlighting the biological continuum between different epilepsies. Genome-wide studies examining common genetic risk factors identified common variants in SCN1A, indicating a convergence of shared pathophysiological pathways in various types of epilepsies. In the era of next-generation sequencing, however, the GGEs appear more complex than expected, and small or moderately sized studies give only a limited genetic perspective. Thus, there is a strong impetus for large collaborative investigations on an international level. PMID:26060908

  13. Neurosteroids and epilepsy

    PubMed Central

    Biagini, Giuseppe; Panuccio, Gabriella; Avoli, Massimo

    2016-01-01

    Purpose of review Neurosteroids are a family of compounds synthesized directly in the brain by transforming cholesterol into pregnenolone, which is then converted to compounds such as allopregnanolone and allotetrahydrodeoxycorticosterone. In view of their ability to modulate neurotransmission, neurosteroids may influence the clinical course of epileptic disorders. In this review, we highlight two emerging properties of neurosteroids, that is, their anticonvulsant and antiepileptogenic activities. Recent findings It has been shown that fluctuations in neurosteroid synthesis, such as those seen in response to stress or during the ovarian cycle, determine an increase in seizure threshold. Moreover, increased neurosteroid synthesis, presumably occurring in glial cells during epileptogenesis, delays the appearance of recurrent spontaneous seizures in an animal model of temporal lobe epilepsy; such an effect may be due to augmented tonic γ-aminobutyric acid type A receptor-mediated inhibition. Finally, clinical trials with ganaxolone, an allopregnanolone analogue, have demonstrated beneficial effects in pharmacoresistant epileptic patients, whereas finasteride – which interferes with neurosteroid synthesis – facilitates seizures in catamenial epilepsy. Summary The overall evidence suggests that neurosteroids may represent a novel therapeutic strategy in epileptic disorders and a future perspective to control epileptogenicity. PMID:20160650

  14. Progressive myoclonic epilepsy.

    PubMed

    Satishchandra, P; Sinha, S

    2010-01-01

    Progressive myoclonic epilepsy (PME) is a disease complex and is characterized by the development of relentlessly progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. It encompasses different diagnostic entities and the common causes include Lafora body disease, neuronal ceroid lipofuscinoses, Unverricht-Lundborg disease, myoclonic epilepsy with ragged-red fiber (MERRF) syndrome, sialidoses, dentato-rubro-pallidal atrophy, storage diseases, and some of the inborn errors of metabolism, among others. Recent advances in this area have clarified molecular genetic basis, biological basis, and natural history, and also provided a rational approach to the diagnosis. Most of the large studies related to PME are from south India from a single center, National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore. However, there are a few case reports and small series about Lafora body disease, neuronal ceroid lipofuscinoses and MERRF from India. We review the clinical and research experience of a cohort of PME patients evaluated at NIMHANS over the last two decades, especially the phenotypic, electrophysiologic, pathologic, and genetic aspects. PMID:20739785

  15. Natural approaches to epilepsy.

    PubMed

    Gaby, Alan R

    2007-03-01

    This article reviews research on the use of diet, nutritional supplements, and hormones in the treatment of epilepsy. Potentially beneficial dietary interventions include identifying and treating blood glucose dysregulation, identifying and avoiding allergenic foods, and avoiding suspected triggering agents such as alcohol, aspartame, and monosodium glutamate. The ketogenic diet may be considered for severe, treatment-resistant cases. The Atkins diet (very low in carbohydrates) is a less restrictive type of ketogenic diet that may be effective in some cases. Nutrients that may reduce seizure frequency include vitamin B6, magnesium, vitamin E, manganese, taurine, dimethylglycine, and omega-3 fatty acids. Administration of thiamine may improve cognitive function in patients with epilepsy. Supplementation with folic acid, vitamin B6, biotin, vitamin D, and L-carnitine may be needed to prevent or treat deficiencies resulting from the use of anticonvulsant drugs. Vitamin K1 has been recommended near the end of pregnancy for women taking anticonvulsants. Melatonin may reduce seizure frequency in some cases, and progesterone may be useful for women with cyclic exacerbations of seizures. In most cases, nutritional therapy is not a substitute for anticonvulsant medications. However, in selected cases, depending on the effectiveness of the interventions, dosage reductions or discontinuation of medications may be possible. PMID:17397265

  16. Progressive Myoclonus Epilepsies.

    PubMed

    Kälviäinen, Reetta

    2015-06-01

    The progressive myoclonus epilepsies (PMEs) comprise a group of rare and heterogeneous disorders defined by the combination of action myoclonus, epileptic seizures, and progressive neurologic deterioration. Neurologic deterioration may include progressive cognitive decline, ataxia, neuropathy, and myopathy. The gene defects for the most common forms of PME (Unverricht-Lundborg disease, Lafora disease, several forms of neuronal ceroid lipofuscinoses, myoclonus epilepsy with ragged-red fibers [MERRF], and type 1 and 2 sialidoses) have been identified. The prognosis of a PME depends on the specific disease. Lafora disease, the neuronal ceroid lipofuscinoses, and the neuronopathic form of Gaucher disease have an invariably fatal course. In contrast, Unverricht-Lundborg disease has a much slower progression, and with adequate care many patients have a normal life span. The specific diseases that cause PME are diagnosed by recognition of their age of onset, the associated clinical symptoms, the clinical course, the pattern of inheritance, and by special investigations such as enzyme measurement, skin/muscle biopsy, or gene testing. PMID:26060909

  17. Epilepsy in Dostoevsky's novels.

    PubMed

    Voskuil, Piet H A

    2013-01-01

    Fyodor Mikhailovich Dostoevsky (1821-1881) suffered from epilepsy. Some type of psychopathology can be found in about 25% of the characters of his novels. Some of them have seizures. In at least five of them Dostoevsky clearly intends them to have epilepsy. Others are more likely to be created as people with hysteria or sometimes, for instance, possession. In this essay an inventory is given by more or less comprehensive quotes of different types of seizures in five novels. The seizures are named in the novels with a varying vocabulary based on the concepts of nosology in the 19th century, the knowledge of Dostoevsky of these concepts, his own experiences, and problems in translation and transliteration. In the discussion, analysis of the role these factors played in the understanding of what Dostoevsky really expressed is given attention. Special attention is given to the so-called ecstatic aura. This element of focal epileptic seizures is so rare that in the past the description of it raised doubts on its existence as such and therefore the embellishment by Dostoevsky, describing his own experience and/or that of his epileptic characters Kirillov and Myshkin. The consequence of this analytic approach, however, should not be losing one's amazement of the genius polyphonic creativity of Dostoevsky to integrate so many profound aspects of the human and especially the Russian soul in the characters of his novels. PMID:23485902

  18. Gene therapy in epilepsy

    PubMed Central

    Riban, Véronique; Fitzsimons, Helen L.; During, Matthew J.

    2009-01-01

    SUMMARY Results from animal models suggest gene therapy is a promising new approach for the treatment of epilepsy. Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity. For a successful gene therapy-based treatment, efficient delivery of a transgene to target neurons is also essential. To this end, advances have been made in the areas of cell transplantation and in the development of recombinant viral vectors for gene delivery. Recombinant adeno-associated viral (rAAV) vectors in particular show promise for gene therapy of neurological disorders due to their neuronal tropism, lack of toxicity, and stable persistence in neurons, which results in robust, long-term expression of the transgene. rAAV vectors have been recently used in phase I clinical trials of Parkinson’s disease with an excellent safety profile. Prior to commencement of phase I trials for gene therapy of epilepsy, further preclinical studies are ongoing including evaluation of the therapeutic benefit in chronicmodels of epileptogenesis, as well as assessment of safety intoxicological studies. PMID:18717707

  19. Epilepsy and sports.

    PubMed

    van Linschoten, R; Backx, F J; Mulder, O G; Meinardi, H

    1990-07-01

    Millions of healthy people participate in sport on a regular basis. Moreover, in the last decade patients with chronic disorders have been encouraged to take part in sporting activities as a part of their rehabilitation. Can epileptic patients freely participate in sport or whether they are restricted to a certain extent by their disorder? An important factor is freedom from seizures. If seizures have been controlled for over 2 years the risk of relapse is the same as the risk of a first seizure. The risk of patients drowning or falling, or their epilepsy worsening because they are engaged in sport is thought to be low. Clinical data suggest that the incidence of seizures during sports and exercise is reduced. In the cooling down period, however, seizures tend to occur more frequently. Physicians should encourage epileptic patients to participate in sporting activities to enhance their physical fitness, self-esteem, and social integration. Before giving advice about the most suitable type of sport, the physician should known the patient's medical history, have a good insight into the different types of sport and be able to judge the role and function of sport to the particular patient. With certain precautions virtually all sports are suitable for most epileptic patients and should therefore be encouraged. However, a small minority of hospitalised patients with severe epilepsy need the supervision of qualified trainers, coaches and volunteers. PMID:2197701

  20. Machado de Assis's epilepsy.

    PubMed

    Guerreiro, C A

    1992-09-01

    Machado de Assis (1839-1908) is considered the most important Brazilian writer and a great universal literary figure. Little is know about his medical, personal and family history. He hid his "disease" as much as possible. Machado referred to "strange things" having happened to him in his childhood. He described seizures as "nervous phenomena", "absenses", "my illness". Laet observed a seizure and described it as: "... when Machado approached us and spoke to me in disconnected words. I looked at him in surprise and found his features altered. Knowing that from time to time he had nervous problems, ... and only permitted Machado take the Laranjeiras Street car, when I saw that he was completely well". A photographically documented seizure is shown. Alencar wrote, "The preoccupation with health was frequent: either he was having the consequences of a fit or was foreboding one". It is clear that Machado presented localized symptomatic epilepsy with complex partial seizures secondarily generalized of unknown etiology. The seizures which began in infancy or childhood had remission in adolescence and then recurred in his thirties and became more frequent in his later years. His depression got markedly worse with age. In our opinion, the greatest consequence of Machado's epilepsy, was his psychological suffering due to the prejudice of the times. Despite this Machado showed all his genius, which is still actual and universal. PMID:1308419

  1. A Model of Post-Traumatic Epilepsy After Penetrating Brain Injuries: Effect of Lesion Size and Metal Fragments

    PubMed Central

    Kendirli, M. Tansel; Rose, Dominique T.; Bertram, Edward H.

    2014-01-01

    Objective Penetrating brain injury (PBI) has the highest risk for inducing post-traumatic epilepsy and retained foreign materials such as bullet fragments carry the greatest risk. This study examines the potential contribution of copper, a major component of bullets, to the development of epilepsy following PBI. Methods Anesthetized adult male rats received a penetrating injury from the dorsal cortex to the ventral hippocampus from a high speed small bit drill. In one group of animals, copper wire was inserted into the lesion. Control animals had only the lesion or the lesion plus stainless steel wire (biologically inert foreign body). From 6 to up to 11 months following the injury the rats were monitored intermittently for the development of epilepsy with video-EEG. A separate set of animals was examined for possible acute seizures in the week following the injury. Results 22 of the 23 animals with copper wire developed chronic epilepsy compared to 3 of the 20 control rats (lesion and lesion with stainless steel). Copper was associated with more extensive injury. The control rats with epilepsy had larger lesions. In the acute injury group, there was no difference in the incidence of seizures (83% lesion plus stainless steel, 70% lesion plus copper). Conclusions Copper increases the risk for epilepsy and may increase damage over time, but there were no differences between the groups in the incidence of acute post-injury seizures. Lesion size may contribute to epilepsy development in lesion only animals. Copper maybe an independent risk factor for the development of epilepsy and possible secondary injury, but lesion size also contributes to the development of epilepsy. The consequences of prolonged exposure of the brain to copper observed in these animals may have clinical implications that require further evaluation. PMID:25470332

  2. [Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].

    PubMed

    Jóźwiak, Sergiusz

    2007-01-01

    Epilepsy is one of the most frequent neurological disorders, both in children and adult persons. About 0.5-1% of general population suffer from epilepsy, which means that about 50 million people in the world are affected. First years of life and very late adulthood are periods in human's life particularly predisposing to epilepsy. Repetitive epileptic seizures may cause many life-threatening situations and significantly lower patient's quality of life. To the most serious complications belong status epilepticus and sudden unexpected deaths due to epilepsy (SUDEP). Absences from work or school caused by seizures, difficulties in social life, frequent injuries and necessity of polytherapy are also important for patients. All these factors result in low self-esteem and poor quality of life. The main aim of the treatment was control of epileptic seizures. However, despite of new antiepileptic drugs developed almost every year, in one third of all patients with epilepsy seizures remain out of control. Those patients are regarded to have "drug-resistant epilepsy". Despite of significant scale of the problem, there is no one definition of the phenomenon. In the presented review the authors outline current definitions, recent opinions on pathogenesis and risk factors, and provide practical rules of pharmacotherapy of epilepsy, which should help to restrict drug-resistancy. PMID:17966891

  3. [Images of epilepsy in Shakespeare].

    PubMed

    Breuer, Horst

    2002-01-01

    Epilepsy and the "falling sickness" are mentioned three times in Shakespeare, in Julius Caesar, I.ii, Othello, IV.i., and figuratively in King Lear, II.ii. The present article surveys these passages in the context of modern research findings, literary as well as medico-historical. It adds further material from Renaissance texts and concludes that epilepsy is an omnibus term for a variety of symptoms and pathological conditions, and that Shakespeare's idea of epilepsy is closer to popular stereotypes than has hitherto been assumed. PMID:12365348

  4. Modern management of juvenile myoclonic epilepsy.

    PubMed

    Brodie, Martin J

    2016-06-01

    Juvenile myoclonic epilepsy (JME) is a common genetic epilepsy syndrome usually presenting in adolescence and characterized by myoclonic jerks, predominately in the arms, associated with tonic-clonic seizures and less often generalized absences. Although the evidence base for treating JME is weak, most experts regard sodium valproate as drug of first choice. The recent diktat from the European regulatory agency - recommending that sodium valproate should not be prescribed to female children, adolescents or women of childbearing potential unless other treatments were ineffective or not tolerated - has substantially changed the way JME is being managed in this population. This paper reviews the literature underpinning the pharmacological treatment of JME. Data reporting associated symptoms of frontal lobe dysfunction in some patients with JME are discussed, as is the importance of counselling on lifestyle issues as an essential component of management. Long-term studies examining pharmacological and quality-of-life outcomes are reviewed, indicating a range of different phenotypes and likely genotypes underpinning this fascinating disorder. Lastly, a practical approach to managing JME in young men and women is summarized. PMID:27082040

  5. Talking about epilepsy: Challenges parents face when communicating with their child about epilepsy and epilepsy-related issues.

    PubMed

    O'Toole, Stephanie; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K

    2016-04-01

    The aim of this qualitative study was to explore the challenges that parents of children with epilepsy experienced when engaging in dialog with their child about epilepsy and epilepsy-related issues. Using a qualitative exploratory approach, interviews were conducted with 34 parents of children with epilepsy (aged 6-16years), consisting of 27 mothers and 7 fathers. Data were transcribed verbatim and thematically analyzed. Findings revealed five main themes: normalizing epilepsy, the invisibility of epilepsy, information concealment, fear of misinforming the child, and difficulty in discussing particular epilepsy-related issues. Many of the communicative challenges experienced by parents impacted on their ability to engage openly in parent-child dialog about epilepsy in the home. Parents face specific challenges when choosing to communicate with their child about epilepsy, relating to creating a sense of normality, reducing fear of causing their child worry, and having a lack of epilepsy-related knowledge. Healthcare professionals who work closely with families living with epilepsy should remain mindful of the importance of discussing family communication surrounding epilepsy and the challenges parents of children with epilepsy face when talking about epilepsy within the home. PMID:26900774

  6. Time course evaluation of behavioral impairments in the pilocarpine model of epilepsy.

    PubMed

    Lopes, Mark William; Lopes, Samantha Cristiane; Santos, Danúbia Bonfanti; Costa, Ana Paula; Gonçalves, Filipe Marques; de Mello, Nelson; Prediger, Rui Daniel; Farina, Marcelo; Walz, Roger; Leal, Rodrigo Bainy

    2016-02-01

    Epilepsy is a brain function disorder characterized by unpredictable and recurrent seizures. The majority of patients with temporal lobe epilepsy (TLE), which is the most common type of epilepsy, have to live not only with seizures but also with behavioral alterations, including anxiety, psychosis, depression, and impaired cognitive functioning. The pilocarpine model has been recognized as an animal model of TLE. However, there are few studies addressing behavioral alterations in the maturation phase when evaluating the time course of the epileptogenic process after pilocarpine administration. Therefore, the present work was designed to analyze the neurobehavioral impairments of male adult Wistar rats during maturation and chronic phases in the pilocarpine model of epilepsy. Behavioral tests included: open-field tasks, olfactory discrimination, social recognition, elevated plus maze, and the forced swimming test. The main behavioral alterations observed in both maturation and chronic phases of the pilocarpine model were olfactory and short-term social memory deficits and decrease in the immobility time in the forced swimming test. Moreover, increased anxiety-like responses were only observed in the maturation phase. These findings indicate that early behavioral impairments can be observed in the pilocarpine model during the maturation phase, and these behavioral deficits also occur during the acquired epilepsy (chronic phase). Several of the neurobehavioral impairments that are associated with epilepsy in humans were observed in the pilocarpine-treated rats, thus, rendering this animal model a useful tool to study neuroprotective strategies as well as neurobiological and psychopathological mechanisms associated with epileptogenesis. PMID:26773677

  7. Quality of life in children with well-controlled epilepsy.

    PubMed

    Wildrick, D; Parker-Fisher, S; Morales, A

    1996-06-01

    In our pediatric neurology clinic, we noticed that some of the children and adolescents with well-controlled epilepsy seemed to have difficulty in school, social and family life situations. We postulated that having epilepsy and needing to take daily antiepileptic drugs caused occasional problems in these areas. A questionnaire assessing self concept, home life, school life, social activities and medication issues was developed to explore this issue. Sixty patients with mild epilepsy from our pediatric neurology clinic were surveyed. With an age range of 8-18 years, the mean age of the participants was 12.38 years (SD = 2.93). Thirty-five were females and 25 were males. Twenty had generalized tonic-clonic, 7 absence, 30 partial with motor symptoms, 2 partial with sensory symptoms and 1 unspecified type. Preliminary data indicate statistically significant correlations (p < .05) between children's concerns about seizure activity and self-perceived academic and social difficulties. A simple tool like this questionnaire can be used to help nurses assess quality of life issues in children and adolescents with epilepsy. PMID:8818985

  8. Epilepsy and brain inflammation.

    PubMed

    Vezzani, Annamaria; Aronica, Eleonora; Mazarati, Andrey; Pittman, Quentin J

    2013-06-01

    During the last decade, experimental research has demonstrated a prominent role of glial cells, activated in brain by various injuries, in the mechanisms of seizure precipitation and recurrence. In particular, alterations in the phenotype and function of activated astrocytes and microglial cells have been described in experimental and human epileptic tissue, including modifications in potassium and water channels, alterations of glutamine/glutamate cycle, changes in glutamate receptor expression and transporters, release of neuromodulatory molecules (e.g. gliotransmitters, neurotrophic factors), and induction of molecules involved in inflammatory processes (e.g. cytokines, chemokines, prostaglandins, complement factors, cell adhesion molecules) (Seifert et al., 2006; Vezzani et al., 2011; Wetherington et al., 2008). In particular, brain injury or proconvulsant events can activate microglia and astrocytes to release a number of proinflammatory mediators, thus initiating a cascade of inflammatory processes in brain tissue. Proinflammatory molecules can alter neuronal excitability and affect the physiological functions of glia by paracrine or autocrine actions, thus perturbing the glioneuronal communications. In experimental models, these changes contribute to decreasing the threshold to seizures and may compromise neuronal survival (Riazi et al., 2010; Vezzani et al., 2008). In this context, understanding which are the soluble mediators and the molecular mechanisms crucially involved in glio-neuronal interactions is instrumental to shed light on how brain inflammation may contribute to neuronal hyperexcitability in epilepsy. This review will report the clinical observations in drug-resistant human epilepsies and the experimental findings in adult and immature rodents linking brain inflammation to the epileptic process in a causal and reciprocal manner. By confronting the clinical evidence with the experimental findings, we will discuss the role of specific soluble

  9. Absence of seizures in Rasmussen encephalitis with active inflammation.

    PubMed

    Samanta, Debopam; Gokden, Murat; Albert, Gregory W

    2016-06-01

    Severe focal motor epilepsy is considered a clinical hallmark of Rasmussen encephalitis (RE). The authors report a 6-year-old girl with progressive right sided hemiparesis, loss of language skills, left sided hemispheric atrophy, and brain pathologic features characteristic for RE. The patient did not experience seizures over a 2year period after symptom onset and for several months during follow-up. This report expands the clinical spectrum of RE and suggests that seizures are not a universal symptom of RE. Our patient's quite remarkable neurologic deficits along with active inflammation in the absence of epilepsy supports that, at least in some individuals, unilateral hemispheric progressive inflammation can occur without active seizure activity. PMID:26775150

  10. Guidelines for epilepsy management in India classification of seizures and epilepsy syndromes.

    PubMed

    Ramaratnam, Sridharan; Satishchandra, P

    2010-10-01

    This article is part of the Guidelines for Epilepsy management in India. This article reviews the classification systems used for epileptic seizures and epilepsy and present the recommendations based on current evidence. At present, epilepsy is classified according to seizure type and epilepsy syndrome using the universally accepted International League Against Epilepsy (ILAE) classification of epileptic seizures and epilepsy syndromes. A multi-axial classification system incorporating ictal phenomenology, seizure type, epilepsy syndrome, etiology and impairments is being developed by the ILAE task force. The need to consider age-related epilepsy syndromes is particularly important in children with epilepsy. The correct classification of seizure type and epilepsy syndrome helps the individual with epilepsy to receive appropriate investigations, treatment, and information about the likely prognosis. PMID:21264131

  11. Adolescents' lived experience of epilepsy.

    PubMed

    Eklund, Pernilla Garmy; Sivberg, Bengt

    2003-02-01

    To improve the well-being of adolescents with epilepsy, research is needed on how adolescents cope. In this study, Lazarus' model of stress and coping and Antonovsky's Theory of Sense of Coherence were used as the theoretical framework. The aim was to describe the lived experience of adolescents with epilepsy and their coping skills. The participants were 13-19 years old with an epilepsy diagnosis but without mental retardation or cerebral palsy. The study was performed in southern Sweden at the pediatric department of a university hospital. Semistructured and open-ended interviews were conducted with 13 adolescents. The transcripts were analyzed with manifest and latent content analysis. All the adolescents had developed strategies to cope with the emotional strains caused by epilepsy. They experienced strains from the seizures, limitation of leisure activities, side effects of medication, and feelings of being different. The coping strategies described were finding support, being in control, and experimenting. PMID:12789720

  12. Epilepsy Imaging Study Guideline Criteria

    PubMed Central

    Gaillard, William D; Cross, J Helen; Duncan, John S; Stefan, Hermann; Theodore, William H

    2011-01-01

    Recognition of limited economic resources, as well as potential adverse effects of ‘over testing,’ has increased interest in ‘evidence-based’ assessment of new medical technology. This creates a particular problem for evaluation and treatment of epilepsy, increasingly dependent on advanced imaging and electrophysiology, since there is a marked paucity of epilepsy diagnostic and prognostic studies that meet rigorous standards for evidence classification. The lack of high quality data reflects fundamental weaknesses in many imaging studies but also limitations in the assumptions underlying evidence classification schemes as they relate to epilepsy, and to the practicalities of conducting adequately powered studies of rapidly evolving technologies. We review the limitations of current guidelines and propose elements for imaging studies that can contribute meaningfully to the epilepsy literature. PMID:21740417

  13. Role of Astrocytes in Epilepsy

    PubMed Central

    Coulter, Douglas A.; Steinhäuser, Christian

    2016-01-01

    Astrocytes express ion channels, transmitter receptors, and transporters and, thus, are endowed with the machinery to sense and respond to neuronal activity. Recent studies have implicated that astrocytes play important roles in physiology, but these cells also emerge as crucial actors in epilepsy. Astrocytes are abundantly coupled through gap junctions allowing them to redistribute elevated K+ and transmitter concentrations from sites of enhanced neuronal activity. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization, and function of astroglial K+ and water channels. In addition, malfunction of glutamate transporters and the astrocytic glutamate-converting enzyme, glutamine synthetase, has been observed in epileptic tissue. These findings suggest that dysfunctional astrocytes are crucial players in epilepsy and should be considered as promising targets for new therapeutic strategies. PMID:25732035

  14. Hyper-excitability and epilepsy generated by chronic early-life stress

    PubMed Central

    Dubé, Céline M.; Molet, Jenny; Singh-Taylor, Akanksha; Ivy, Autumn; Maras, Pamela M.; Baram, Tallie Z.

    2015-01-01

    Epilepsy is more prevalent in populations with high measures of stress, but the neurobiological mechanisms are unclear. Stress is a common precipitant of seizures in individuals with epilepsy, and may provoke seizures by several mechanisms including changes in neurotransmitter and hormone levels within the brain. Importantly, stress during sensitive periods early in life contributes to ‘brain programming’, influencing neuronal function and brain networks. However, it is unclear if early-life stress influences limbic excitability and promotes epilepsy. Here we used an established, naturalistic model of chronic early-life stress (CES), and employed chronic cortical and limbic video-EEGs combined with molecular and cellular techniques to probe the contributions of stress to age-specific epilepsies and network hyperexcitability and identify the underlying mechanisms. In control male rats, EEGs obtained throughout development were normal and no seizures were observed. EEGs demonstrated epileptic spikes and spike series in the majority of rats experiencing CES, and 57% of CES rats developed seizures: Behavioral events resembling the human age-specific epilepsy infantile spasms occurred in 11/23 (48%), accompanied by EEG spikes and/or electrodecrements, and two additional rats (9%) developed limbic seizures that involved the amygdala. Probing for stress-dependent, endogenous convulsant molecules within amygdala, we examined the expression of the pro-convulsant neuropeptide corticotropin-releasing hormone (CRH), and found a significant increase of amygdalar--but not cortical--CRH expression in adolescent CES rats. In conclusion, CES of limited duration has long-lasting effects on brain excitability and may promote age-specific seizures and epilepsy. Whereas the mechanisms involved require further study, these findings provide important insights into environmental contributions to early-life seizures. PMID:25884016

  15. Epilepsy in Dante's poetry.

    PubMed

    Mula, Marco

    2016-04-01

    Dante Alighieri is the greatest Italian poet and one of the most important writers in Western literature. He is best known for the epic poem "Commedia", later named "La Divina Commedia" that has profoundly influenced not only poetic imagination but also all subsequent allegorical creations of imaginary worlds in literature. This paper examines the poetic description of some episodes of loss of consciousness in Dante's poetry discussing how and why typical elements of epileptic seizures have been used. On the 750th anniversary of Dante's birth, his poetry still remains to be an inspiring source of debate and reflection. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID:26907926

  16. Psychobehavioral therapy for epilepsy.

    PubMed

    Tang, Venus; Michaelis, Rosa; Kwan, Patrick

    2014-03-01

    Growing evidence suggests a bidirectional interaction between epileptic seizures and psychological states, fuelling the interest in the development and application of psychobehavioral therapy for people with epilepsy (PWE). The objective of this article is to review the various psychobehavioral therapies in regard to their application, hypothesized mechanisms, and effectiveness. Most psychobehavioral therapy aims at improving psychological well-being and seizure control. Behavioral approaches, cognitive-behavioral therapy (CBT), and mind-body interventions are the most widely applied approaches for PWE. Cognitive-behavioral therapy, mind-body approaches, and multimodel educative interventions have consistently demonstrated positive effects on enhancing well-being. Nevertheless, the effects on seizure control remain inconsistent, partly attributable to small clinical trials and inadequate control groups. Assessor-blinded randomized controlled trials with sufficient power and carefully defined therapeutic components corresponding with objective and subjective outcome measures are recommended for future trial designs. PMID:24418662

  17. [Twilight states in epilepsy].

    PubMed

    Kharchevnikov, G M; Boldyrev, A I

    1980-01-01

    A total of 82 epileptic patients with twilight states were studied. Such conditions were more frequently encountered in epilepsy due to neuroinfections and brain trauma. Twilight states, as a rule, appear after several years from the onset of the disease, when it was not treated or inadequately treated and indicate an unfavorable development of the epileptic process. It is desirable that twilight states be classified as developing rapidly and with a retarded course. In rapidly developing epileptic disorders the epileptic focus on EEG was more frequently seen in the temporal areas, while in protractd disorders it was seen in the subcortical and stem brain structures. Pneumoencephalography revealed pronounced scarry and cystoadhesive lesions. Twilight states should be differentiated with temporal psychomotor attacks by certain clinical signs. PMID:6774534

  18. Cognitive disorders in pediatric epilepsy.

    PubMed

    Jambaqué, I; Pinabiaux, C; Lassonde, M

    2013-01-01

    Childhood epilepsy may cause cognitive disorders and the intellectual quotient is indeed not normally distributed in epileptic children, a fair proportion of whom show an IQ in the deficient range. Some epileptic syndromes happen during vulnerability periods of brain maturation and interfere with the development of specific cognitive functions. This is the case for the Landau-Kleffner syndrome, which generally appears during speech development and affects language. Similarly, West syndrome - or infantile spasms - is an epileptogenic encephalopathy appearing during the first years of life and induces a major delay in social and oculo-motor development. Specific impairments can also be identified in partial childhood epilepsies in relation with seizure focus localization. For instance, left temporal and frontal epilepsies are frequently associated with verbal impairments. Moreover, episodic memory disorders have been described in children suffering from temporal lobe epilepsy whereas executive deficits (planning, self-control, problem solving) have been reported in frontal lobe epilepsy. In most cases, including its mildest forms, childhood epilepsy induces attention deficits, which may affect academic achievement. These observations militate in favor of individual neuropsychological assessments as well as early interventions in order to provide the child with an optimal individualized treatment program. PMID:23622216

  19. Dynamics of networks during absence seizure's on- and offset in rodents and man

    PubMed Central

    Lüttjohann, Annika; van Luijtelaar, Gilles

    2015-01-01

    Network mechanisms relevant for the generation, maintenance and termination of spike-wave discharges (SWD), the neurophysiological hallmark of absence epilepsy, are still enigmatic and widely discussed. Within the last years, however, improvements in signal analytical techniques, applied to both animal and human fMRI, EEG, MEG, and ECoG data, greatly increased our understanding and challenged several, dogmatic concepts of SWD. This review will summarize these recent data, demonstrating that SWD are not primary generalized, are not sudden and unpredictable events. It will disentangle different functional contributions of structures within the cortico-thalamo-cortical system, relevant for the generation, generalization, maintenance, and termination of SWD and will present a new “network based” scenario for these oscillations. Similarities and differences between rodent and human data are presented demonstrating that in both species a local cortical onset zone of SWD exists, although with different locations; that in both some forms of cortical and thalamic precursor activity can be found, and that SWD occur through repetitive cyclic activity between cortex and thalamus. The focal onset zone in human data could differ between patients with varying spatial and temporal dynamics; in rats the latter is still poorly investigated. PMID:25698972

  20. Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy

    PubMed Central

    Park, So Young; Kwon, Hye Eun; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Dong Seok; Kim, Heung Dong

    2013-01-01

    Background and Purpose: The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures. Methods: 48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children’s Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery. Results: Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children’s epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children’s improvement in cognitive and behavior issues. Conclusions: Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues. PMID:24649473

  1. Febrile Seizures and Epilepsy: Possible Outcomes

    MedlinePlus

    ... whether they could increase the risk of developing epilepsy later. Febrile seizures are defined as seizures that ... brains of patients who underwent surgery for severe epilepsy. 3 The children with FSE were com- pared ...

  2. PET studies in epilepsy

    PubMed Central

    Sarikaya, Ismet

    2015-01-01

    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced 11C-flumazenil (GABAA-cBDZ) and 18F-MPPF (5-HT1A serotonin) and increased 11C-cerfentanil (mu opiate) and 11C-MeNTI (delta opiate) bindings in the area of seizure. 11C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that 11C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous sclerosis complex

  3. Bathing Epilepsy: Report of Three Caucasian Cases

    PubMed Central

    Dashi, Florian; Seferi, Arsen; Rroji, Arben; Enesi, Eugen; Petrela, Mentor

    2015-01-01

    Introduction: Bathing epilepsy is a specific type of reflex epilepsy triggered by domestic bathing in water. It is a geographically specific epilepsy syndrome that is more prevalent in India Cases in Caucasian population are very rarely reported. These cases share many similar clinical features and a similar prognosis to the Indian cases. Case report: We describe three cases of bathing epilepsy in Albanian population; two cases with well controlled seizures and one with drug-resistant seizures. PMID:26005279

  4. Sex differences in the neurobiology of epilepsy: a preclinical perspective.

    PubMed

    Scharfman, Helen E; MacLusky, Neil J

    2014-12-01

    When all of the epilepsies are considered, sex differences are not always clear, despite the fact that many sex differences are known in the normal brain. Sex differences in epilepsy in laboratory animals are also unclear, although robust effects of sex on seizures have been reported, and numerous effects of gonadal steroids have been shown throughout the rodent brain. Here we discuss several reasons why sex differences in seizure susceptibility are unclear or are difficult to study. Examples of robust sex differences in laboratory rats, such as the relative resistance of adult female rats to the chemoconvulsant pilocarpine compared to males, are described. We also describe a novel method that has shed light on sex differences in neuropathology, which is a relatively new technique that will potentially contribute to sex differences research in the future. The assay we highlight uses the neuronal nuclear antigen NeuN to probe sex differences in adult male and female rats and mice. In females, weak NeuN expression defines a sex difference that previous neuropathological studies have not described. We also show that in adult rats, social isolation stress can obscure the normal effects of 17β-estradiol to increase excitability in area CA3 of the hippocampus. These data underscore the importance of controlling behavioral stress in studies of seizure susceptibility in rodents and suggest that behavioral stress may be one factor that has led to inconsistencies in outcomes of sex differences research. These and other issues have made it difficult to translate our increasing knowledge about the effects of gonadal hormones on the brain to improved treatment for men and women with epilepsy. PMID:25058745

  5. Sex differences in the neurobiology of epilepsy: a preclinical perspective

    PubMed Central

    Scharfman, Helen E.; MacLusky, Neil J.

    2014-01-01

    When all of the epilepsies are considered, sex differences are not always clear, despite the fact that many sex differences are known in the normal brain. Sex differences in epilepsy in laboratory animals are also unclear, although robust effects of sex on seizures have been reported, and numerous effects of gonadal steroids have been shown throughout the rodent brain. Here we discuss several reasons why sex differences in seizure susceptibility are unclear or are difficult to study. Examples of robust sex differences in laboratory rats, such as the relative resistance of adult female rats to the chemoconvulsant pilocarpine compared to males, are described. We also describe a novel method that has shed light on sex differences in neuropathology, which is a relatively new techniques that will potentially contribute to sex differences research in the future. The assay we highlight uses the neuronal nuclear antigen NeuN to probe sex differences in adult male and female rats and mice. In females, weak NeuN expression defines a sex difference that previous neuropathological studies have not described. We also show that in adult rats, social isolation stress can obscure the normal effects of 17β-estradiol to increase excitability in area CA3 of hippocampus. These data underscore the importance of controlling behavioral stress in studies of seizure susceptibility in rodents and suggest that behavioral stress may be one factor that has led to inconsistencies in outcomes of sex differences research. These and other issues have made it difficult to translate our increasing knowledge about the effects of gonadal hormones on the brain to improved treatment for men and women with epilepsy. PMID:25058745

  6. Epilepsy Workshop for Public School Personnel.

    ERIC Educational Resources Information Center

    Rassel, Gary; And Others

    1981-01-01

    Epilepsy is one of the most misunderstood and stigmatized disorders in society. A four-hour workshop was conducted over two days with the first two hours discussing types of epilepsy, causes, treatment, and medication. The second part of the study focused on social and psychological implications of epilepsy. (JN)

  7. Epilepsy in prisons: a diagnostic survey.

    PubMed

    Gunn, J; Fenton, G

    1969-11-01

    A previous study has suggested that epilepsy is commoner in prisons than in the general population. We devised a standard definition of "epilepsy" and then interviewed a representative sample of the "epileptics" in prisons. The results confirmed the initial conclusion, and showed the point prevalence of epilepsy in prison and Borstals to be at least 7.1/1,000 men. PMID:5386266

  8. Epilepsy surgery: recommendations for India.

    PubMed

    Chandra, P Sarat; Tripathi, Manjari

    2010-04-01

    The following article recommends guidelines for epilepsy surgery for India. This article reviews the indications, the various surgical options available and the outcome of surgery for drug resistant epilepsy based on current evidence. Epilepsy surgery is a well-established option for patients who have been diagnosed to have drug resistant epilepsy (DRE) (on at least two appropriate, adequate anti-epileptic drugs (AEDs) (either in monotherapy or in combination) with continuing seizures), where the presurgical work-up has shown concordance of structural imaging (magnetic resonance imaging) and electrical mapping data (electroencephalography (EEG), video EEG). There may be a requirement of functional imaging techniques in a certain number of DRE like positron emission tomography (PET), single photon emission tomography, (SPECT)). Invasive monitoring should be restricted to a few when all noninvasive investigations are inconclusive, there is a dual pathology or there is a discordance of noninvasive data. The types of surgery could be curative (resective surgeries: amygdalo hippocampectomy, lesionectomy and multilobar resections; functional surgeries: hemispherotomy) and palliative (multiple subpial transaction, corpus callosotomy, vagal nerve stimulation). Epilepsy surgery in indicated cases has a success range from 50 to 86% in achieving seizure freedom as compared with <5% success rate with AEDs only in persons with DRE. Centers performing surgery should be categorized into Level I and Level II. PMID:20814490

  9. Evidence of Absence software

    USGS Publications Warehouse

    Dalthorp, Daniel; Huso, Manuela M. P.; Dail, David; Kenyon, Jessica

    2014-01-01

    Evidence of Absence software (EoA) is a user-friendly application used for estimating bird and bat fatalities at wind farms and designing search protocols. The software is particularly useful in addressing whether the number of fatalities has exceeded a given threshold and what search parameters are needed to give assurance that thresholds were not exceeded. The software is applicable even when zero carcasses have been found in searches. Depending on the effectiveness of the searches, such an absence of evidence of mortality may or may not be strong evidence that few fatalities occurred. Under a search protocol in which carcasses are detected with nearly 100 percent certainty, finding zero carcasses would be convincing evidence that overall mortality rate was near zero. By contrast, with a less effective search protocol with low probability of detecting a carcass, finding zero carcasses does not rule out the possibility that large numbers of animals were killed but not detected in the searches. EoA uses information about the search process and scavenging rates to estimate detection probabilities to determine a maximum credible number of fatalities, even when zero or few carcasses are observed.

  10. Toxoplasma gondii and Epilepsy.

    PubMed

    Ayaz, Erol; Türkoğlu, Şule Aydın; Orallar, Hayriye

    2016-06-01

    Toxoplasma gondii is a zoonotic parasite can be seen in all the vital organ; in the acute phase, it can be found in the blood, cerebrospinal fluid, semen, tears, saliva, urine, and in almost all body fluids. Transplasental infection can lead to fetal damage and miscarriage. Its last hosts are felines and intermediate hosts are all mammals, including humans. People infected by the ingestion of meat containing cysts in undercooked or raw, are thrown oocysts with cat felines By taking in water and food, from mother to fetus transplacental way, the infected organ transplantation, blood transfusion, laboratory accidents and kaprofaj transmitted by mechanical vectors of the invertebrates. Suppression of the immune system is being transformed to the shape and texture of the cysts with bradyzoite. The parasite settles in the cells of the tissue cysts and causes change in the cellular mechanisms, such as cytokinin task. Depending on changes and type of neurotransmitter (GABA, glutamate, serotonin, dopamine) levels in CSF in ions (Ca, K, Cl, Mg), it is believed that there is a change in their concentration. In this review, literature about the relationship between T. gondii and epilepsy and epileptiform activity the importance of parasites, which settle in the brain, will be highlighted. PMID:27594290

  11. [Epilepsy and driving].

    PubMed

    Adam, Claude

    2015-10-01

    Epilepsy contributes little to road traffic accidents (0.25% of accidents) compared, for instance, to alcohol abuse (at least 30 times higher). Current factors, such as age and sex, or other chronic medical conditions also increase the risk of road traffic accidents but do not carry driving restrictions. So, the European Commission fairly established rules permitting individuals having experienced one or more epileptic seizures to drive if their road accident risk is low. Road accident risk related to epileptic seizures in various clinical situations is evaluated by the driving license commission, mainly with the aid of criteria based on seizure-free periods. A person who has had an epileptic seizure should notify the authorities. He should be advised by treating physician not to drive before. In case of an authorisation, any new relevant event should be notified to the authorities in the course of legal follow-up. Improvements of the current regulations by European data registries are under way. PMID:26482490

  12. Photosensitivity and epilepsy.

    PubMed

    Verrotti, Alberto; Trotta, Daniela; Salladini, Carmela; di Corcia, Giovanna; Chiarelli, Francesco

    2004-08-01

    Photosensitive epilepsy is a well-known condition characterized by seizures in patients who show photoparoxysmal responses on electroencephalography (EEG) elicited by intermittent photic stimulation. Photoparoxysmal responses can be defined as epileptiform EEG responses to intermittent photic stimulation or to other visual stimuli of everyday life and are frequently found in nonepileptic children. The modern technologic environment has led to a dramatic increase in exposure to potential trigger stimuli; nowadays, television and video games are among the most common triggers in daily life. There is ample evidence for genetic transmission of photoparoxysmal responses; systematic family studies have provided data for an autosomal dominant mode of inheritance with age-dependent penetrance for photosensitivity. The age of maximum penetrance is between 5 and 15 years. The prognosis for control of seizures induced by visual stimulation is generally very good. The large majority of patients do not need anticonvulsant therapy, but, when needed, the drug of choice is valproate. Stimulus avoidance and stimulus modification can be an effective treatment in some patients and can sometimes be combined with antiepileptic drug treatment. PMID:15605465

  13. Challenges in the pharmacological management of epilepsy and its causes in the elderly.

    PubMed

    Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Aguglia, Umberto

    2016-04-01

    Epilepsy represents the third most common neurological disorders in the elderly after cerebrovascular disorders and dementias. The incidence of new-onset epilepsy peaks in this age group. The most peculiar aetiologies of late-onset epilepsy are stroke, dementia, and brain tumours. However, aetiology remains unknown in about half of the patients. Diagnosis of epilepsy may be challenging due to the frequent absence of ocular witnesses and the high prevalence of seizure-mimics (i.e. transient ischemic attacks, syncope, transient global amnesia or vertigo) in the elderly. The diagnostic difficulties are even greater when patients have cognitive impairment or cardiac diseases. The management of late-onset epilepsy deserves special considerations. The elderly can reach seizure control with low antiepileptic drugs (AEDs) doses, and seizure-freedom is possible in the vast majority of patients. Pharmacological management should take into account pharmacokinetics and pharmacodynamics of AEDs and the frequent occurrence of comorbidities and polytherapy in this age group. Evidences from double-blind and open-label studies indicate lamotrigine, levetiracetam and controlled-release carbamazepine as first line treatment in late-onset epilepsy. PMID:26896787

  14. List-learning and verbal memory profiles in childhood epilepsy syndromes.

    PubMed

    Schraegle, William A; Nussbaum, Nancy L; Stefanatos, Arianna K

    2016-09-01

    Findings of material-specific influences on memory performance in pediatric epilepsy are inconsistent and merit further investigation. This study compared 90 children (aged 6years to 16years) with childhood absence epilepsy (CAE), frontal lobe epilepsy (FLE), and temporal lobe epilepsy (TLE) to determine whether they displayed distinct list-learning and verbal memory profiles on the California Verbal Learning Test - Children's Version (CVLT-C). Group comparison identified greater risk of memory impairment in children with TLE and FLE syndromes but not for those with CAE. While children with TLE performed worst overall on Short Delay Free Recall, groups with TLE and FLE performed similarly on Long Delay Free Recall. Contrast indices were then employed to explore these differences. Children with TLE demonstrated a significantly greater retroactive interference (RI) effect compared with groups with FLE and CAE. Conversely, children with FLE demonstrated a significantly worse learning efficiency index (LEI), which compares verbal memory following repetition with initial recall of the same list, than both children with TLE and CAE. These findings indicated shallow encoding related to attentional control for children with FLE and retrieval deficits in children with TLE. Finally, our combined sample showed significantly higher rates of extreme contrast indices (i.e., 1.5 SD difference) compared with the CVLT-C standardization sample. These results underscore the high prevalence of memory dysfunction in pediatric epilepsy and offer support for distinct patterns of verbal memory performance based on childhood epilepsy syndrome. PMID:27484747

  15. [Epilepsy with higher brain dysfunction].

    PubMed

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Kuroda, Takeshi; Fujita, Kazuhisa; Itaya, Kazuhiro; Ishigaki, Seiichiro; Kawamura, Mitsuru

    2013-02-01

    Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease. PMID:23399676

  16. Epilepsy and metaphors in literature.

    PubMed

    Wolf, Peter

    2016-04-01

    This topic has two different aspects: seizures and epilepsy used as metaphors and seizures described in metaphors. Whereas some metaphors are unique and have high literary value, others can be categorized in prototypical groups. These include sexual metaphors; metaphors of strong emotions, of life crises and breakdown, and also of exultation; religious metaphors; and metaphors of weakness which mostly belong to older literature. Writers with epilepsy, in their literary texts, rarely talk about seizures in metaphors. Authors who do this sometimes seem to use reports that they have received from afflicted persons. The most common metaphors for seizures belong to the realms of dreams and of strong sensory impressions (visual, auditory). More rarely, storm and whirlwind are used as literary metaphors for seizures. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID:26936537

  17. Current Topics in Epilepsy Surgery.

    PubMed

    Usui, Naotaka

    2016-05-15

    This article reviews the current topics in the field of epilepsy surgery. Each type of epilepsy is associated with a different set of questions and goals. In mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS), postoperative seizure outcome is satisfactory. A recent meta-analysis revealed superior seizure outcome after anterior temporal lobectomy compared with selective amygdalohippocampectomy; in terms of cognitive outcome; however, amygdalohippocampectomy may be beneficial. In temporal lobe epilepsy with normal magnetic resonance imaging (MRI), postoperative seizure outcome is not as favorable as it is in MTLE with HS; further improvement of seizure outcome in these cases is necessary. Focal cortical dysplasia is the most common substrate in intractable neocortical epilepsy, especially in children, as well as in MRI-invisible neocortical epilepsy. Postoperative seizure-free outcome is approximately 60-70%; further diagnostic and therapeutic improvement is required. Regarding diagnostic methodology, an important topic currently under discussion is wideband electroencephalogram (EEG) analysis. Although high-frequency oscillations and ictal direct current shifts are considered important markers of epileptogenic zones, the clinical significance of these findings should be clarified further. Regarding alternatives to surgery, neuromodulation therapy can be an option for patients who are not amenable to resective surgery. In addition to vagus nerve stimulation, intracranial stimulation such as responsive neurostimulation or anterior thalamic stimulation is reported to have a modest seizure suppression effect. Postoperative management such as rehabilitation and antiepileptic drug (AED) management is important. It has been reported that postoperative rehabilitation improves postoperative employment status. Pre- and post-operative comprehensive care is mandatory for postoperative improvement of quality of life. PMID:26984452

  18. Current Topics in Epilepsy Surgery

    PubMed Central

    USUI, Naotaka

    2016-01-01

    This article reviews the current topics in the field of epilepsy surgery. Each type of epilepsy is associated with a different set of questions and goals. In mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS), postoperative seizure outcome is satisfactory. A recent meta-analysis revealed superior seizure outcome after anterior temporal lobectomy compared with selective amygdalohippocampectomy; in terms of cognitive outcome; however, amygdalohippocampectomy may be beneficial. In temporal lobe epilepsy with normal magnetic resonance imaging (MRI), postoperative seizure outcome is not as favorable as it is in MTLE with HS; further improvement of seizure outcome in these cases is necessary. Focal cortical dysplasia is the most common substrate in intractable neocortical epilepsy, especially in children, as well as in MRI-invisible neocortical epilepsy. Postoperative seizure-free outcome is approximately 60–70%; further diagnostic and therapeutic improvement is required. Regarding diagnostic methodology, an important topic currently under discussion is wideband electroencephalogram (EEG) analysis. Although high-frequency oscillations and ictal direct current shifts are considered important markers of epileptogenic zones, the clinical significance of these findings should be clarified further. Regarding alternatives to surgery, neuromodulation therapy can be an option for patients who are not amenable to resective surgery. In addition to vagus nerve stimulation, intracranial stimulation such as responsive neurostimulation or anterior thalamic stimulation is reported to have a modest seizure suppression effect. Postoperative management such as rehabilitation and antiepileptic drug (AED) management is important. It has been reported that postoperative rehabilitation improves postoperative employment status. Pre- and post-operative comprehensive care is mandatory for postoperative improvement of quality of life. PMID:26984452

  19. Antiepileptic and Antiepileptogenic Performance of Carisbamate after Head Injury in the Rat: Blind and Randomized Studies

    PubMed Central

    Eastman, Clifford L.; Verley, Derek R.; Fender, Jason S.; Stewart, Tessandra H.; Nov, Eytan; Curia, Giulia

    2011-01-01

    Carisbamate (CRS) exhibits broad acute anticonvulsant activity in conventional anticonvulsant screens, genetic models of absence epilepsy and audiogenic seizures, and chronic spontaneous motor seizures arising after chemoconvulsant-induced status epilepticus. In add-on phase III trials with pharmacoresistant patients CRS induced <30% average decreases in partial-onset seizure frequency. We assessed the antiepileptogenic and antiepileptic performance of subchronic CRS administration on posttraumatic epilepsy (PTE) induced by rostral parasaggital fluid percussion injury (rpFPI), which closely replicates human contusive closed head injury. Studies were blind and randomized, and treatment effects were assessed on the basis of sensitive electrocorticography (ECoG) recordings. Antiepileptogenic effects were assessed in independent groups of control and CRS-treated rats, at 1 and 3 months postinjury, after completion of a 2-week prophylactic treatment initiated 15 min after injury. The antiepileptic effects of 1-week CRS treatments were assessed in repeated measures experiments at 1 and 4 months postinjury. The studies were powered to detect ∼50 and ∼40% decreases in epilepsy incidence and frequency of seizures, respectively. Drug/vehicle treatment, ECoG analysis, and [CRS]plasma determination all were performed blind. We detected no antiepileptogenic and an equivocal transient antiepileptic effects of CRS despite [CRS]plasma comparable with or higher than levels attained in previous preclinical and clinical studies. These findings contrast with previous preclinical data demonstrating large efficacy of CRS, but agree with the average effect of CRS seen in clinical trials. The data support the use of rpFPI-induced PTE in the adolescent rat as a model of pharmacoresistant epilepsy for preclinical development. PMID:21123672

  20. Antiepileptic and antiepileptogenic performance of carisbamate after head injury in the rat: blind and randomized studies.

    PubMed

    Eastman, Clifford L; Verley, Derek R; Fender, Jason S; Stewart, Tessandra H; Nov, Eytan; Curia, Giulia; D'Ambrosio, Raimondo

    2011-03-01

    Carisbamate (CRS) exhibits broad acute anticonvulsant activity in conventional anticonvulsant screens, genetic models of absence epilepsy and audiogenic seizures, and chronic spontaneous motor seizures arising after chemoconvulsant-induced status epilepticus. In add-on phase III trials with pharmacoresistant patients CRS induced < 30% average decreases in partial-onset seizure frequency. We assessed the antiepileptogenic and antiepileptic performance of subchronic CRS administration on posttraumatic epilepsy (PTE) induced by rostral parasaggital fluid percussion injury (rpFPI), which closely replicates human contusive closed head injury. Studies were blind and randomized, and treatment effects were assessed on the basis of sensitive electrocorticography (ECoG) recordings. Antiepileptogenic effects were assessed in independent groups of control and CRS-treated rats, at 1 and 3 months postinjury, after completion of a 2-week prophylactic treatment initiated 15 min after injury. The antiepileptic effects of 1-week CRS treatments were assessed in repeated measures experiments at 1 and 4 months postinjury. The studies were powered to detect ~50 and ~40% decreases in epilepsy incidence and frequency of seizures, respectively. Drug/vehicle treatment, ECoG analysis, and [CRS](plasma) determination all were performed blind. We detected no antiepileptogenic and an equivocal transient antiepileptic effects of CRS despite [CRS](plasma) comparable with or higher than levels attained in previous preclinical and clinical studies. These findings contrast with previous preclinical data demonstrating large efficacy of CRS, but agree with the average effect of CRS seen in clinical trials. The data support the use of rpFPI-induced PTE in the adolescent rat as a model of pharmacoresistant epilepsy for preclinical development. PMID:21123672

  1. Ictal Asystole in Focal Epilepsy

    PubMed Central

    Sarwal, Aarti

    2015-01-01

    Ictal bradyarrhythmias are rare episodes occurring in patients with or without a past cardiac history. These episodes go unnoticed unless the patient is monitored on simultaneous video-electroencephalogram and 1-lead electrocardiogram. Recognizing ictal bradyarrhythmias is important, since episodes may predispose patients to sudden, unexplained death in epilepsy. We present 2 cases of ictal asystole in patients with right temporal lobe epilepsy. The first patient had seizures refractory to medical therapy and received a pacemaker. The seizures in the second patient responded well to antiepileptic medication, and a pacemaker was deferred. These cases highlight the differing cardiovascular treatment options for ictal asystole. PMID:26425256

  2. Novel medications for epilepsy.

    PubMed

    Fattore, Cinzia; Perucca, Emilio

    2011-11-12

    Despite the introduction of many second-generation antiepileptic drugs (AEDs) in the last 2 decades, the proportion of individuals with pharmacoresistant epilepsy has not been reduced substantially compared with the late 1960s. All currently available AEDs also have limitations in terms of adverse effects and susceptibility to be involved in clinically important drug-drug interactions. Therefore, the search for potentially more effective and better tolerated agents is continuing. This article reviews the pharmacological and clinical profile of the latest compounds to receive marketing authorization. Since the beginning of 2008, three novel AEDs, lacosamide, eslicarbazepine acetate and retigabine (also known as ezogabine), have become commercially available in Europe, with lacosamide and retigabine also being licensed in the US. All three agents are indicated for the adjunctive treatment of focal seizures in adults. Eslicarbazepine acetate is a produg for eslicarbazepine, which acts by blocking voltage-dependent sodium channels. Lacosamide enhances the slow inactivation phase of voltage-dependent sodium channels, and retigabine potentiates neuronal M-currents by opening Kv 7.2-7.5 potassium channels. All three agents, which are well absorbed from the gastrointestinal tract, exhibit linear pharmacokinetics. Lacosamide is also available as an intravenous formulation intended as replacement therapy for patients temporarily unable to take oral medications. All three drugs are eliminated partly unchanged in urine and partly by biotransformation through glucuronide conjugation (eslicarbazepine, retigabine), N-acetylation (retigabine) and oxidative demethylation (lacosamide). The half-life is in the order of 8-20 hours for eslicarbazepine, 12-16 hours for lacosamide and 6-10 hours for retigabine. Based on the limited information available to date, the ability of these agents to cause pharmacokinetic drug interactions appears to be relatively modest, although

  3. Charles Dickens (1812-1870) and epilepsy.

    PubMed

    Larner, A J

    2012-08-01

    To coincide with the bicentenary of the birth of Charles Dickens (1812-1870), accounts of epilepsy found in his novels and journalism have been collated and analyzed. From these, it may be inferred that Dickens was clearly aware of the difference between epilepsy and syncope and recognized different types of epilepsy and that seizures could be fatal. Speculations that Dickens himself suffered from epilepsy are not corroborated. Dickens's novelistic construction of epilepsy as a marker of criminality, as in the characters of Monks in Oliver Twist and Bradley Headstone in Our Mutual Friend, and perhaps of mental abnormality, was in keeping with conventional contemporary views of epilepsy, but his journalistic descriptions of individuals with epilepsy confined in the workhouse system indicate an awareness of the inadequacy of their care. PMID:22704997

  4. Anthropometric Indices in Children With Refractory Epilepsy

    PubMed Central

    AMINZADEH, Vahid; DALILI, Setila; ASHOORIAN, Yalda; KOHMANAEE, Shahin; HASSANZADEH RAD, Afagh

    2016-01-01

    Objective We aimed to assess the effect of body mass index (BMI) on reducing the risk of refractory seizure due to lipoid tissue factors. Materials & Methods This matched case-control study, consisted of cases (Patients with refractory epilepsy) and controls (Healthy children) referred to 17 Shahrivar Hospital, Guilan University of Medical Sciences, Guilan, Iran during 2013-2014. Data were gathered by a form including demographic characteristics, type of epilepsy, predominant time of epilepsy, therapeutic approach, frequency of epilepsy, time of disease onset and anthropometric indices. We measured anthropometric indices and transformed them into Z-scores. Data were reported by descriptive statistics (mean and standard deviation) and analyzed by Pearson correlation coefficient, paired t test and multinomial regression analysis test using SPSS 19. Results There was no significant difference between sex groups regarding anthropometric indices. Generalized and focal types of epilepsies were noted on 57.5% and 38.75% of patients, respectively. Daytime epilepsies happened in 46.25% of patients and 33.75% noted no predominant time for epilepsies. Clinicians indicated poly-therapy for the majority of patients (92.5%). The most common onset times for epilepsies were 36-72 months for 32.5% of patients. Lower onset time indicated lower frequency of refractory epilepsies. Although, there was significant difference between Zheight and predominant time of epilepsies but no significant relation was found between types of epilepsies and frequency of epilepsies with anthropometric indices. Using multivariate regression analysis by backward LR, Zweight and birth weight were noted as the predicting factors of refractory epilepsies. Conclusion This effect may be because of leptin. Therefore, researchers recommend further investigations regarding this issue in children with epilepsy. PMID:27057188

  5. Spatiotemporal dynamics of optogenetically induced and spontaneous seizure transitions in primary generalized epilepsy

    PubMed Central

    Truccolo, Wilson; Wang, Jing; Nurmikko, Arto V.

    2014-01-01

    Transitions into primary generalized epileptic seizures occur abruptly and synchronously across the brain. Their potential triggers remain unknown. We used optogenetics to causally test the hypothesis that rhythmic population bursting of excitatory neurons in a local neocortical region can rapidly trigger absence seizures. Most previous studies have been purely correlational, and it remains unclear whether epileptiform events induced by rhythmic stimulation (e.g., sensory/electrical) mimic actual spontaneous seizures, especially regarding their spatiotemporal dynamics. In this study, we used a novel combination of intracortical optogenetic stimulation and microelectrode array recordings in freely moving WAG/Rij rats, a model of absence epilepsy with a cortical focus in the somatosensory cortex (SI). We report three main findings: 1) Brief rhythmic bursting, evoked by optical stimulation of neocortical excitatory neurons at frequencies around 10 Hz, induced seizures consisting of self-sustained spike-wave discharges (SWDs) for about 10% of stimulation trials. The probability of inducing seizures was frequency-dependent, reaching a maximum at 10 Hz. 2) Local field potential power before stimulation and response amplitudes during stimulation both predicted seizure induction, demonstrating a modulatory effect of brain states and neural excitation levels. 3) Evoked responses during stimulation propagated as cortical waves, likely reaching the cortical focus, which in turn generated self-sustained SWDs after stimulation was terminated. Importantly, SWDs during induced and spontaneous seizures propagated with the same spatiotemporal dynamics. Our findings demonstrate that local rhythmic bursting of excitatory neurons in neocortex at particular frequencies, under susceptible ongoing brain states, is sufficient to trigger primary generalized seizures with stereotypical spatiotemporal dynamics. PMID:25552645

  6. The medium chain triglyceride diet and intractable epilepsy.

    PubMed Central

    Sills, M A; Forsythe, W I; Haidukewych, D; MacDonald, A; Robinson, M

    1986-01-01

    Fifty children with drug resistant epilepsy were treated with the Medium Chain Triglyceride (MCT) Emulsion diet. Eight achieved complete control of seizures (four without anticonvulsant drugs), and with the addition of anticonvulsants four had seizures reduced in frequency by 90% and 10 by 50-90%. The best results were obtained with astatic myoclonic and absence seizures, but control of seizures was improved in four children with tonic-clonic and three with complex partial seizures. Food given at the same time as MCT helped to reduce side effects, and an extra dose of MCT before bedtime improved control of nocturnal seizures. PMID:3101615

  7. Hsp60 response in experimental and human temporal lobe epilepsy

    PubMed Central

    Gammazza, Antonella Marino; Colangeli, Roberto; Orban, Gergely; Pierucci, Massimo; Di Gennaro, Giancarlo; Bello, Margherita Lo; D'Aniello, Alfredo; Bucchieri, Fabio; Pomara, Cristoforo; Valentino, Mario; Muscat, Richard; Benigno, Arcangelo; Zummo, Giovanni; de Macario, Everly Conway; Cappello, Francesco; Di Giovanni, Giuseppe; Macario, Alberto J. L.

    2015-01-01

    The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management. PMID:25801186

  8. Chronodependency and provocative factors in juvenile myoclonic epilepsy.

    PubMed

    Kasteleijn-Nolst Trenité, Dorothée G A; de Weerd, Al; Beniczky, Sándor

    2013-07-01

    In juvenile myoclonic epilepsy (JME), occurrence of seizures and epileptiform EEG discharges is influenced by internal and external factors. The most important internal factor is the chronodependency: the occurrence of myoclonic jerks in the early morning is one of the hallmarks of JME. Approximately two-thirds of the patients with JME report that seizures are provoked by a variety of general factors like stress, fatigue, fever, and sleep and more specific precipitants like flashing sunlight, music, reading, thinking, and excess alcohol. The prevalence rate of photosensitivity (photoparoxysmal EEG response) in patients with JME ranges from 8 to 90%; it is seen more often in females and adolescents and depends on drug use. Since both JME and photosensitivity are connected with generalized types of epilepsy and myoclonus, the two traits are comorbid for that reason. Epileptiform EEG discharges can be provoked by other activation methods: sleep, hyperventilation, and specific cognitive tasks. Attention seems to have a non-specific, inhibitory effect of the epileptiform discharges. Hyperventilation can induce absence seizures in patients with JME, while cognitive tasks are efficient in precipitating myoclonic seizures. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really? PMID:23756476

  9. Quantifying interictal metabolic activity in human temporal lobe epilepsy

    SciTech Connect

    Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.; Christenson, P.D.; Zhang, J.X.; Phelps, M.E.; Kuhl, D.E. )

    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 single 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.

  10. Sleep Disorders, Epilepsy, and Autism

    ERIC Educational Resources Information Center

    Malow, Beth A.

    2004-01-01

    The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum…

  11. [PET and SPECT in epilepsy].

    PubMed

    Setoain, X; Carreño, M; Pavía, J; Martí-Fuster, B; Campos, F; Lomeña, F

    2014-01-01

    Epilepsy is one of the most frequent chronic neurological disorders, affecting 1-2% of the population. Patients with complex partial drug resistant episodes may benefit from a surgical treatment consisting in the excision of the epileptogenic area. Localization of the epileptogenic area was classically performed with video-EEG and magnetic resonance (MR). Recently, functional neuroimaging studies of Nuclear Medicine, positron emission tomography (PET) and single photon emission tomography (SPECT) have demonstrated their utility in the localization of the epileptogenic area prior to surgery. Ictal SPECT with brain perfusion tracers show an increase in blood flow in the initial ictal focus, while PET with (18)FDG demonstrates a decrease of glucose metabolism in the interictal functional deficit zone. In this review, the basic principles and methodological characteristics of the SPECT and PET in epilepsy are described. The ictal SPECT injection mechanism, different patterns of perfusion based on the time of ictal, postictal or interictal injection are detailed and the different diagnostic sensitivities of each one of these SPECT are reviewed. Different methods of analysis of the images with substraction and fusion systems with the MR are described. Similarly, the injection methodology, quantification and evaluation of the images of the PET in epilepsy are described. Finally, the main clinical indications of SPECT and PET in temporal and extratemporal epilepsy are detailed. PMID:24565567

  12. The Physiopathogenesis of the Epilepsies.

    ERIC Educational Resources Information Center

    Gastaut, Henri; And Others

    Material is discussed in articles by 40 contributors. Concerning physiopathogenesis of epilepsies there are introductory notes, two articles on genetics, one on neurophysiological and metabolic mechanisms, two on renal failure, a discussion of convulsive seizure and water intoxication, three articles on hypoglycemia, one on electroclinical…

  13. The return of dissociation as absence within absence.

    PubMed

    Gurevich, Hayuta

    2014-12-01

    My aim is to translate Ferenczi's central concepts of the intrapsychic impact and imprint of early developmental trauma into both revived and contemporary conceptualizations. The concept of dissociation was renounced by Freud, yet it is returning as a cornerstone of recent trauma theories. Ferenczi used the concept of "repression," but used it in the sense of an intrapsychic imprint of early external trauma that fragments consciousness, that is, as dissociation. Furthermore, early trauma is double: an absence of protection that threatens existence of the self, combined with an absence of attachment and of recognition of this threat and terror; thus it is an absence-within-absence. This contemporary conceptualization entails a widening of the intrapsychic realm to include an intersubjective one, and regards dissociation as a unique and complex intrapsychic absence, which is a negative of the external absence-within-absence in the early environment. PMID:25434884

  14. Sexual performance and precontact 50-kHz ultrasonic vocalizations in WAG/Rij rats: effects of opioid receptor treatment.

    PubMed

    Bialy, Michal; Strefnel, Michal; Nikolaev-Diak, Anna; Socha, Anna; Nikolaev, Evgeni; Boguszewski, Pawel M

    2014-10-01

    WAG/Rij rats are genetically selected animals that model absence epilepsy in rats. Ultrasonic vocalizations and sexual behavior - both ethologically relevant markers of reward system functioning - are poorly described in this strain. The aim of our experiment was to investigate reward-dependent precontact 50-kHz vocalizations (PVs) and copulatory behavior as well as the effects of opioid receptor treatment on such behaviors in sexually experienced WAG/Rij males and rats from two control strains: Sprague-Dawley and Crl: Han Wistar. We analyzed the effects of the opioid receptor antagonist naltrexone (3 mg/kg) and the agonist morphine (1 mg/kg) administration. Additionally, we analyzed the initiation of copulation in sexually naïve males before drug treatment. A significantly lower number of sexually naïve WAG/Rij rats initiated copulation. Sexually experienced WAG/Rij males differed at the control session (after physiological saline treatment) compared with Sprague-Dawley rats: WAG/Rij rats displayed more 50-kHz precontact vocalizations and had longer mount and intromission latencies, longer ejaculation latency, longer postejaculatory latency to exploration, longer 22-kHz vocalization duration after ejaculation, and longer postejaculatory intromission latency. Compared with Crl: Han Wistar rats, WAG/Rij males displayed longer mount latency and shorter 22-kHz vocalization duration. Neither naltrexone nor morphine affected PVs in all groups. On the other hand, opioid receptor treatment differently influenced the number of intromissions required to achieve ejaculation and 22-kHz postejaculatory vocalization duration in WAG/Rij rats than in both control groups. This suggests functional differences in the opioid system in this strain. As a result of the number of males that initiated copulation as well as the number of intromissions to ejaculation and 22-kHz postejaculatory vocalizations which all depend on D1 receptor activation, we suggest that the proportion of

  15. 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

  16. Sleep and Epilepsy: Strange Bedfellows No More

    PubMed Central

    St. Louis, Erik K.

    2012-01-01

    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. PMID:23539488

  17. 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. PMID:23539488

  18. Sexual problems in people with refractory epilepsy.

    PubMed

    Henning, Oliver J; Nakken, Karl O; Træen, Bente; Mowinckel, Petter; Lossius, Morten

    2016-08-01

    Sexual dysfunction is an important but often neglected aspect of epilepsy. The objective of this study was to explore the prevalence and types of sexual problems in patients with epilepsy and compare the results with similar data obtained from a representative sample of the general population. At the National Centre for Epilepsy in Norway, 171 of 227 consecutive adult inpatients and outpatients with epilepsy (response rate: 75.3%) and their neurologists participated in a questionnaire study about epilepsy and sexuality. The results were compared with data available from 594 adult Norwegians who had completed the same questionnaire. Patients with epilepsy had a significantly higher prevalence of sexual problems (women: 75.3% vs. 12.0%; men: 63.3% vs. 9.6%). The most commonly reported problems (>30%) were reduced sexual desire, orgasm problems, erection problems, and vaginal dryness. The patients reported considerable dissatisfaction regarding sexual functioning. Significantly more sexual problems were found in patients of both sexes with reduced quality of life and in women with symptoms of depression. We found no significant association between sexual problems and age of epilepsy onset, type of epilepsy, or use of enzyme-inducing antiepileptic drugs. Whereas age at sexual debut did not differ between the patients with epilepsy and the general population, men with epilepsy had a lower number of partners during the last 12months, and the proportion of women with a low frequency of intercourse was higher in the group with epilepsy. In conclusion, sexual problems are significantly greater in Norwegian patients with epilepsy than in the general adult population. As no single epilepsy type or treatment could be identified as a specific predisposing factor, it seems likely that there are multiple causes underlying our results, including both organic and psychosocial factors. PMID:27371882

  19. Current management and surgical outcomes of medically intractable epilepsy.

    PubMed

    Ramey, Wyatt L; Martirosyan, Nikolay L; Lieu, Corinne M; Hasham, Hasnain A; Lemole, G Michael; Weinand, Martin E

    2013-12-01

    Epilepsy is one of the most common neurologic disorders in the world. While anti-epileptic drugs (AEDs) are the mainstay of treatment in most cases, as many as one-third of patients will have a refractory form of disease indicating the need for a neurosurgical evaluation. Ever since the first half of the twentieth century, surgery has been a major treatment option for epilepsy, but the last 10-15 years in particular has seen several major advances. As shown in relatively recent studies, resection is more effective for medically intractable epilepsy (MIE) than AED treatment alone, which is why most clinicians now endorse a neurosurgical consultation after approximately two failed regimens of AEDs, ultimately leading to decreased healthcare costs and increased quality of life. Temporal lobe epilepsy (TLE) is the most common form of MIE and comprises about 80% of epilepsy surgeries with the majority of patients gaining complete seizure-freedom. As the number of procedures and different approaches continues to grow, temporal lobectomy remains consistently focused on resection of mesial structures such as the amygdala, hippocampus, and parahippocampal gyrus while preserving as much of the neocortex as possible resulting in optimum seizure control with minimal neurological deficits. MIE originating outside the temporal lobe is also effectively treated with resection. Though not as successful as TLE surgery because of their frequent proximity to eloquent brain structures and more diffuse pathology, epileptogenic foci located extratemporally also benefit from resection. Favorable seizure outcome in each of these procedures has heavily relied on pre-operative imaging, especially since the massive surge in MRI technology just over 20 years ago. However, in the absence of visible lesions on MRI, recent improvements in secondary imaging modalities such as fluorodeoxyglucose positron emission computed tomography (FDG-PET) and single-photon emission computed tomography (SPECT

  20. Consciousness as a useful concept in epilepsy classification

    PubMed Central

    Blumenfeld, Hal; Meador, Kimford J.

    2014-01-01

    Summary Impaired consciousness has important practical consequences for people living with epilepsy. Recent pathophysiologic studies show that seizures with impaired level of consciousness always affect widespread cortical networks and subcortical arousal systems. In light of these findings and their clinical significance, efforts are underway to revise the International League Against Epilepsy (ILAE) 2010 report to include impaired consciousness in the classification of seizures. Lüders and colleagues have presented one such effort, which we discuss here. We then propose an alternative classification of impaired consciousness in epilepsy based on functional neuroanatomy. Some seizures involve focal cortical regions and cause selective deficits in the content of consciousness but without impaired overall level of consciousness or awareness. These include focal aware conscious seizures (FACS) with lower order cortical deficits such as somatosensory or visual impairment as well as FACS with higher cognitive deficits including ictal aphasia or isolated epileptic amnesia. Another category applies to seizures with impaired level of consciousness leading to deficits in multiple cognitive domains. For this category, we believe the terms “dyscognitive” or “dialeptic” should be avoided because they may create confusion. Instead we propose that seizures with impaired level of consciousness be described based on underlying pathophysiology. Widespread moderately severe deficits in corticothalamic function are seen in absence seizures and in focal impaired consciousness seizures (FICS), including many temporal lobe seizures and other focal seizures with impaired consciousness. Some simple responses or automatisms may be preserved in these seizures. In contrast, generalized tonic–clonic seizures usually produce widespread severe deficits in corticothalamic function causing loss of all meaningful responses. Further work is needed to understand and prevent impaired

  1. Losartan prevents acquired epilepsy via TGF-β signaling suppression

    PubMed Central

    Bar-Klein, Guy; Cacheaux, Luisa P.; Kamintsky, Lyn; Prager, Ofer; Weissberg, Itai; Schoknecht, Karl; Cheng, Paul; Kim, Soo Young; Wood, Lydia; Heinemann, Uwe; Kaufer, Daniela; Friedman, Alon

    2014-01-01

    Objective Acquired epilepsy is frequently associated with structural lesions following trauma, stroke and infections. While seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin-mediated transforming growth factor β (TGF-β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-β signaling and tested the efficacy of blocking the TGF-β pathway in preventing epilepsy. Methods We addressed the role of TGF-β signaling in epiletogenesis in two different rat models of vascular injury, combining in vitro and in vivo biochemical assays, gene expression, magnetic resonance and direct optical imaging for blood-brain barrier (BBB) permeability and vascular reactivity. Long-term electrocorticographic (ECoG) recordings were acquired in freely behaving animals. Results We demonstrate that serum-derived albumin preferentially induces activation of the activin receptor-like kinase 5 (ALK5) pathway of TGF-β receptor I in astrocytes. We further show that the angiotensin II type 1 receptor antagonist (AT1), losartan, previously identified as a blocker of peripheral TGF-β signaling, effectively blocks albumin-induced TGF-β activation in the brain. Most importantly, losartan prevents the development of delayed recurrent spontaneous seizures, an effect that persists weeks after drug withdrawal. Interpretation TGF-β signaling, activated in astrocytes by serum-derived albumin, is involved in epileptogenesis. We propose losartan, an FDA-approved drug, as an efficient anti-epileptogenic therapy for epilepsy associated with vascular injury. PMID:24659129

  2. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    MedlinePlus

    ... myoclonic epilepsy spinal muscular atrophy with progressive myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... All Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  3. Epilepsy, cognition, and neuropsychiatry (Epilepsy, Brain, and Mind, part 2)

    PubMed Central

    Korczyn, Amos D.; Schachter, Steven C.; Brodie, Martin J.; Dalal, Sarang S.; Engel, Jerome; Guekht, Alla; Hecimovic, Hrvoje; Jerbi, Karim; Kanner, Andres M.; Landmark, Cecilie Johannessen; Mares, Pavel; Marusic, Petr; Meletti, Stefano; Mula, Marco; Patsalos, Philip N.; Reuber, Markus; Ryvlin, Philippe; Štillová, Klára; Tuchman, Roberto; Rektor, Ivan

    2016-01-01

    Epilepsy is, of course, not one disease but rather a huge number of disorders that can present with seizures. In common, they all reflect brain dysfunction. Moreover, they can affect the mind and, of course, behavior. While animals too may suffer from epilepsy, as far as we know, the electrical discharges are less likely to affect the mind and behavior, which is not surprising. While the epileptic seizures themselves are episodic, the mental and behavioral changes continue, in many cases, interictally. The episodic mental and behavioral manifestations are more dramatic, while the interictal ones are easier to study with anatomical and functional studies. The following extended summaries complement those presented in Part 1. PMID:23764496

  4. [Neuropsychology, plasticity and childhood epilepsy].

    PubMed

    Lassonde, Maryse; Sauerwein, Hannelore C

    2007-11-01

    Epilepsy is one of the most frequent childhood disorders. While most cases are well controlled, approximately 30-50% are resistant to medical treatment. In these cases, neurosurgery may be an option. Since 1979, our team at the Sainte-Justine Hospital in Montreal has studied the impact of epilepsy on the psycho-motor and cognitive development of the affected children. The aim of a first series of studies was to explore the extent and limits of cerebral plasticity by investigating the neuropsychological sequelae of early versus late callosotomy and hemispherectomy. In keeping with the plasticity hypothesis, the results revealed that the children who were operated before puberty showed fewer deficits than those operated during adolescence or adulthood. However, the compensatory mechanisms available to them appeared to be limited with respect to the nature and complexity of the information they can process. For instance, young children having undergone section of the corpus callosum resembled individuals born without a corpus callosum (callosal agenesis) in that there did not show the typical disconnection deficits seen in adult ''split-brain'' patients. However, they exhibited deficits on tasks requiring interhemispheric integration of motor and visuo-motor information. By the same token, hemispherectomy patients were still able to make visual judgements in their ''blind'' visual field but they were found to be impaired on a variety of visual and auditory tasks (localization of a sound sources in space) requiring the participation of both hemispheres. In a second series of studies, carried out in collaboration with a Parisian team, we intended to describe the neuropsychological profile of focal epilepsies, specifically frontal and temporal epilepsy. Contrary to the common belief that childhood epilepsy would result in diffuse impairments, we were able to demonstrate that children manifest the same localized deficits as adult patients. In studies presently underway in

  5. Complex single gene disorders and epilepsy.

    PubMed

    Merwick, Aine; O'Brien, Margaret; Delanty, Norman

    2012-09-01

    Epilepsy is a heterogeneous group of disorders, often associated with significant comorbidity, such as intellectual disability and skin disorder. The genetic underpinnings of many epilepsies are still being elucidated, and we expect further advances over the coming 5 years, as genetic technology improves and prices fall for whole exome and whole genome sequencing. At present, there are several well-characterized complex epilepsies associated with single gene disorders; we review some of these here. They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene. These disorders are important in informing genetic testing to confirm a diagnosis and to permit better understanding of the variability in phenotype-genotype correlation. PMID:22946725

  6. Voxel-based morphometry and epilepsy.

    PubMed

    Yasuda, Clarissa Lin; Betting, Luiz Eduardo; Cendes, Fernando

    2010-06-01

    Voxel-based morphometry is an automated technique for MRI analyses, developed to study differences in brain morphology and frequently used to study patients with diverse disorders. In epilepsy, it has been used to investigate areas with reduction or increase of gray and white matter, in different syndromes (i.e., temporal lobe epilepsy, focal cortical dysplasia and generalized epilepsies). In temporal lobe epilepsy, voxel-based morphometry showed gray/white matter atrophy extending beyond the atrophic hippocampus. These widespread abnormalities have been associated with seizure frequency, epilepsy duration, incidence of precipitating factors, cognitive dysfunction and surgical outcome. In generalized epilepsies, gray matter abnormalities were identified mainly in the thalamus and frontal cortex, reinforcing the role of the thalamocortical network in the mechanisms of generalized seizures. PMID:20518612

  7. [Epilepsy And Driving Ability: The New Guideline].

    PubMed

    Kurthen, Martin

    2015-10-28

    The Swiss Guideline concerning epilepsy and driving has recently been revised. Recommendations have changed significantly in several respects. Some modifications arise indirectly from a change in the overall concept of epilepsy. As a consequence of the application of the new ILAE definition and diagnostic criteria for epilepsy, there are now cases in which the diagnosis of epilepsy is established even after one single seizure. Furthermore, a concept of imminent epilepsy was introduced to identify patients without seizures, but with a high risk of a first seizure within twelve months. On the other hand, the concept of a "resolved epilepsy" was established to loosen driving regulations for longterm seizure-free patients. In addition, the new guideline provides differential recommendations for provoked vs. unprovoked seizures in several clinical constellations. PMID:26953368

  8. Chronotypes in Patients with Epilepsy: Does the Type of Epilepsy Make a Difference?

    PubMed

    Kendis, Hallie; Baron, Kelly; Schuele, Stephan U; Patel, Bhavita; Attarian, Hrayr

    2015-01-01

    Circadian rhythms govern all biological functions. Circadian misalignment has a major impact on health. Late chronotype is a risk factor for circadian misalignment which in turn can affect the control of seizures in epilepsy patients. We compared a group of 87 confirmed epilepsy patients regardless of subtypes with age- and sex-matched healthy controls. We compared generalized epilepsy patients with localization related epilepsy patients and with healthy controls. We found that primary generalized epilepsy patients were 5 times more likely to have a late chronotype than healthy controls. We did not find any significant differences between localization related epilepsy patients and healthy controls or between the overall epilepsy cohort and healthy controls. Generalized epilepsy patients are more likely to be evening types as compared to those with focal epilepsy or subjects without epilepsy. Epilepsy patients do not experience the same age related increase in morningness as do age-matched healthy controls. This is important in regard to timing of AED, identifying and preventing sleep deprivation, and integrating chronotype evaluations and chronotherapy in comprehensive epilepsy care. Further studies, using objective phase markers or the impact of chronotherapy on seizure control, are necessary. PMID:26078488

  9. Ian Curtis: Punk rock, epilepsy, and suicide.

    PubMed

    Tuft, Mia; Gjelsvik, Bergljot; Nakken, Karl O

    2015-11-01

    Ian Curtis was the front man of the post-punk band Joy Division. He suffered from epilepsy and actively incorporated his experiences of the disease in his lyrics. Curtis had frequent epileptic seizures, both on and off stage. After dying from suicide in 1980, he became a legend in the post-punk milieu. The impact which the epilepsy, the epilepsy treatment, and comorbid depression had on his artistic life and premature death is not well known. PMID:26496010

  10. Genetics of Epilepsy in Clinical Practice

    PubMed Central

    2015-01-01

    Genetics should now be part of everyday clinical epilepsy practice. Good data exist to provide empiric risks based on epilepsy syndrome diagnosis. Investigation of the molecular basis of some epilepsies is now a practical clinical task and is of clear value to the patient and family. In some cases, specific therapeutic decisions can now be made based on genetic findings, and this scenario of precision therapy is likely to increase in the coming years. PMID:26316866

  11. [Psychoses and epilepsy. A case study].

    PubMed

    Verhoeven, W M A; Gunning, W B; Tuerlings, J H A M; Egger, J I M; Tuinier, S

    2006-01-01

    Over the last few decades much research has been done into the raised level of psychiatric comorbidity in epilepsy. On the basis of a case study of a patient suffering from post-ictal psychoses we explain the psychiatric differential diagnosis within the framework of epilepsy and we investigate the frequent psychiatric side-effects of anticonvulsants. It is concluded that the links between epilepsy and psychiatric symptoms are complex and that the neuropsychiatry of epilepsy is concerned with syndromes that are unique and do notfit into modern psychiatric classification systems. PMID:17086946

  12. Treatment issues for personality disorders in epilepsy.

    PubMed

    Trimble, Michael

    2013-03-01

    This article supports a view that certain personality disturbances in epilepsy should be viewed as associated with the cerebral abnormalities that also lead to seizures. Herein I discuss two main variants: that related to temporal lobe epilepsy and that associated with juvenile myoclonic epilepsy. In view of its controversial nature, I also comment on the link between aggression and epilepsy. Recommendations for treatment include psychological and social therapies with further advice about the use of antiepileptic drugs (AEDs) and psychotropic medications in these conditions. PMID:23458465

  13. Counseling Epilepsy Patients on Driving and Employment.

    PubMed

    Krumholz, Allan; Hopp, Jennifer L; Sanchez, Ana M

    2016-05-01

    People with epilepsy identify driving and employment among their major concerns. People with controlled seizures may be permitted to drive in every state in the United States, but people with uncontrolled seizures are restricted from licensure. Unemployment and underemployment for people with epilepsy are serious problems that depend on the frequency and type of seizure disorder and associated medical and psychological problems. Most jobs, with reasonable accommodation by employers, are suitable for people with epilepsy. Federal protections through the Americans with Disabilities Act confer civil rights protection by law on people with disabilities such as epilepsy. PMID:27086988

  14. Diagnostic, treatment, and surgical imaging in epilepsy.

    PubMed

    Nagae, Lidia Mayumi; Lall, Neil; Dahmoush, Hisham; Nyberg, Eric; Mirsky, David; Drees, Cornelia; Honce, Justin M

    2016-01-01

    Dedicated epilepsy centers are growing in hospitals throughout the USA and abroad, with a continuously increasing role of imaging in multidisciplinary meetings. Imaging is paramount in diagnosis, treatment, and surgical decision-making in lesional and nonlesional epileptic disease. Besides being up-to-date with technical developments in imaging that may make an impact in patient care, familiarity with clinical and surgical aspects of epilepsy is fundamental to better understanding of patient management. The present article intends to revisit diagnostic, therapeutic, and surgical imaging in epilepsy. Finally, with the increase in frequency of epilepsy management-related procedures and their hardware, MRI safety issues are discussed. PMID:27317207

  15. Symptomatic Epilepsies due to Cerebrovascular Diseases

    PubMed Central

    Dakaj, Nazim; Shatri, Nexhat; Isaku, Enver; Zeqiraj, Kamber

    2014-01-01

    Introduction: Cerebro-vascular diseases (CVD) are the leading cause of symptomatic epilepsies. This study aims to investigate: a) Frequency of epilepsy in patients with CVD; b) Correlation of epilepsy with the type of CVD (ischemic and hemorrhage) and with age. Methodology: It is analyzed medical documentation of 816 hospitalized patients with CVD in the clinic of Neurology in University Clinical Center (UCC) during the period January - December 2010. The study included data on patients presenting with epileptic seizures after CVD, and those with previously diagnosed epilepsy, are not included in the study. The diagnosis of CVD, are established in clinical neurological examination and the brain imaging (computer tomography and magnetic resonance imaging). The diagnosis of epilepsy is established by the criteria of ILAE (International League against Epilepsy) 1983, and epileptic seizures are classified according to the ILAE classification, of 1981. Results: Out of 816 patients with CVD, 692 were with ischemic stroke and 124 with hemorrhage. From 816 patients, epileptic seizures had 81 (10%), of which 9 patients had been diagnosed with epilepsy earlier and they are not included in the study. From 72 (99%) patients with seizures after CVD 25 (33%) have been with ischemia, whereas 47 (67%) with hemorrhage. Conclusion: CVD present fairly frequent cause of symptomatic epilepsies among patients treated in the clinic of Neurology at UCC (about 10%). The biggest number of patients with epilepsy after CVD was with intracerebral hemorrhage. PMID:25685086

  16. Channelopathies can cause epilepsy in man.

    PubMed

    Steinlein, Ortrud K

    2002-01-01

    Idiopathic epilepsies, which account for up to 40% of all epilepsies, are mainly caused by genetic factors. Most idiopathic epilepsies are due to oligogenic or multifactorial rather than monogenetic inheritance. Nevertheless, most of what is known today about the molecular genetics of idiopathic epilepsies has been found by analysing large families with rare monogenetic forms of the disease. For the first time, gene defects can be linked to certain epilepsies. Mutations in the CHRNA4 or CHRNB subunits of the neuronal nicotinic acetylcholine receptor lead to familial nocturnal frontal lobe epilepsy, while defects in the voltage-gated potassium channels KCNQ2 and KCNQ3 have recently been found to cause benign familial neonatal convulsions. The voltage-gated sodium channel subunits SCN1B, SCN1A and SCN2A as well as the GABRG2 subunit of the GABA(A) receptor are involved in the pathology of the newly described syndrome generalized epilepsy with febrile seizures plus. These rare monogenetic epilepsies can serve as models for further genetic analysis of the common forms of idiopathic epilepsies. PMID:11888238

  17. The Epilepsy Spectrum: Targeting Future Research Challenges.

    PubMed

    Holmes, Gregory L; Noebels, Jeffrey L

    2016-01-01

    There have been tremendous recent advances in our understanding of the biological underpinnings of epilepsy and associated comorbidities that justify its representation as a spectrum disorder. Advances in genetics, electrophysiology, and neuroimaging have greatly improved our ability to differentiate, diagnose, and treat individuals with epilepsy. However, we have made little overall progress in preventing epilepsy, and the number of patients who are cured remains small. Likewise, the comorbidities of epilepsy are often underdiagnosed or not adequately treated. In this article, we suggest a few areas in which additional research will likely pay big dividends for patients and their families. PMID:27371672

  18. Epilepsy Care in Ontario: An Economic Analysis of Increasing Access to Epilepsy Surgery

    PubMed Central

    Bowen, James M.; Snead, O. Carter; Chandra, Kiran; Blackhouse, Gord; Goeree, Ron

    2012-01-01

    Background In August 2011 a proposed epilepsy care model was presented to the Ontario Health Technology Advisory Committee (OHTAC) by an Expert Panel on a Provincial Strategy for Epilepsy Care in Ontario. The Expert Panel recommended leveraging existing infrastructure in the province to provide enhanced capacity for epilepsy care. The point of entry for epilepsy care and the diagnostic evaluation for surgery candidacy and the epilepsy surgery would occur at regional and district epilepsy centres in London, Hamilton, Toronto, and Ottawa and at new centres recommended for northern and eastern Ontario. This economic analysis report was requested by OHTAC to provide information about the estimated budgetary impact on the Ontario health care system of increasing access to epilepsy surgery and to examine the cost-effectiveness of epilepsy surgery in both children and adults. Methods A prevalence-based “top-down” health care system budgetary impact model from the perspective of the Ministry of Health and Long-Term Care was developed to estimate the potential costs associated with expanding health care services to increase access to epilepsy care in general and epilepsy surgery in particular. A 5-year period (i.e., 2012–2016) was used to project annual costs associated with incremental epilepsy care services. Ontario Health Survey estimates of epilepsy prevalence, published epilepsy incidence data, and Canadian Census results for Ontario were used to approximate the number of individuals with epilepsy in the province. Applying these population estimates to data obtained from a recent field evaluation study that examined patterns of care and costs associated with epilepsy surgery in children, a health care system budget impact was calculated and the total costs and incremental costs associated with increasing access to surgery was estimated. In order to examine the cost-effectiveness of epilepsy surgery in children, a decision analysis compared epilepsy surgery to

  19. Pharmacological treatment of epilepsy today.

    PubMed

    Benna, P; Bergamasco, B

    1986-01-01

    The pharmacological treatment of epilepsy has not gone through remarkable changes in recent years. Treatment is based on few first choice drugs, the mechanism of action of which we do not yet know exactly. These include: phenobarbital, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam. Choice of drug is determined by the kind of seizures presented by the patient, while successful treatment is determined by the kind of epilepsy. The present trend is the use of first line drugs in monotherapy, fixing individually the dosage according to the plasma levels. The results obtained with the GABA-agonists (progabide, gamma-vinyl GABA) and with some of the calcium-antagonists (flunarizine) seem promising. PMID:2886407

  20. Surgical strategies for pediatric epilepsy

    PubMed Central

    Guan, Jian; Karsy, Michael; Ducis, Katrina

    2016-01-01

    Pediatric epilepsy is a debilitating condition that impacts millions of patients throughout the world. Approximately 20–30% of children with recurrent seizures have drug-resistant epilepsy (DRE). For these patients, surgery offers the possibility of not just seizure freedom but significantly improved neurocognitive and behavioral outcomes. The spectrum of surgical options is vast, ranging from outpatient procedures such as vagus nerve stimulation to radical interventions including hemispherectomy. The thread connecting all of these interventions is a common goal—seizure freedom, an outcome that can be achieved safely and durably in a large proportion of patients. In this review, we discuss many of the most commonly performed surgical interventions and describe the indications, complications, and outcomes specific to each. PMID:27186522

  1. mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis.

    PubMed

    Citraro, Rita; Leo, Antonio; Constanti, Andrew; Russo, Emilio; De Sarro, Giovambattista

    2016-05-01

    Several preclinical and some clinical studies have revealed that the mammalian target of rapamycin (mTOR) signaling pathway is involved in both genetic and acquired epilepsy syndromes. Excessive activation of mTOR signaling, as a consequence of loss-of-function of genes encoding for tuberous sclerosis complex (TSC) 1 and 2, is linked to the development of cortical malformations and epilepsy. This mTOR hyperactivation is associated with different epileptogenic conditions under the term of 'mTORopathies' such as tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly and ganglioglioma. mTOR overactivation produces brain abnormalities that include dysplastic neurons, abnormal cortical organization and astrogliosis. mTOR inhibitors (e.g. rapamycin) have consistent protective effects in various genetic (e.g. TSC models and WAG/Rij rats) and acquired (e.g. kainate or pilocarpine post-status epilepticus) epilepsy animal models. Furthermore, clinical studies in patients with TSC and cortical dysplasia (CD) have confirmed the effectiveness of mTOR inhibitors also in epileptic patients. Therefore, mTOR is currently a very good candidate as a target for epilepsy and epileptogenesis. This review describes the relevance of the mTOR pathway to epileptogenesis and its potential as a therapeutic target in epilepsy treatment by presenting the most recent findings on mTOR inhibitors. PMID:27049136

  2. New In Vitro Phenotypic Assay for Epilepsy: Fluorescent Measurement of Synchronized Neuronal Calcium Oscillations

    PubMed Central

    Pacico, Nathalie; Mingorance-Le Meur, Ana

    2014-01-01

    Research in the epilepsy field is moving from a primary focus on controlling seizures to addressing disease pathophysiology. This requires the adoption of resource- and time-consuming animal models of chronic epilepsy which are no longer able to sustain the testing of even moderate numbers of compounds. Therefore, new in vitro functional assays of epilepsy are needed that are able to provide a medium throughput while still preserving sufficient biological context to allow for the identification of compounds with new modes of action. Here we describe a robust and simple fluorescence-based calcium assay to measure epileptiform network activity using rat primary cortical cultures in a 96-well format. The assay measures synchronized intracellular calcium oscillations occurring in the population of primary neurons and is amenable to medium throughput screening. We have adapted this assay format to the low magnesium and the 4-aminopyridine epilepsy models and confirmed the contribution of voltage-gated ion channels and AMPA, NMDA and GABA receptors to epileptiform activity in both models. We have also evaluated its translatability using a panel of antiepileptic drugs with a variety of modes of action. Given its throughput and translatability, the calcium oscillations assay bridges the gap between simplified target-based screenings and compound testing in animal models of epilepsy. This phenotypic assay also has the potential to be used directly as a functional screen to help identify novel antiepileptic compounds with new modes of action, as well as pathways with previously unknown contribution to disease pathophysiology. PMID:24416277

  3. Clinical Genetic Testing in Epilepsy

    PubMed Central

    2015-01-01

    New technologies for mutation detection in the human genome have greatly increased our understanding of epilepsy genetics. Application of genomic technologies in the clinical setting allows for more efficient genetic diagnosis in some patients; therefore, it is important to understand the types of tests available and the types of mutations that can be detected. Making a genetic diagnosis improves overall patient care by enhancing prognosis and recurrence risk counseling and informing treatment decisions. PMID:26316867

  4. Sustained Reduction of Cerebellar Activity in Experimental Epilepsy

    PubMed Central

    Rijkers, Kim; Moers-Hornikx, Véronique M. P.; Hemmes, Roelof J.; Aalbers, Marlien W.; Temel, Yasin; Vles, Johan S. H.; Hoogland, Govert

    2015-01-01

    Clinical and experimental evidence suggests a role for the cerebellum in seizure control, while no data are available on cerebellar activity between seizures. We hypothesized that interictal regional activity of the deep cerebellar nuclei is reduced in epilepsy and tested this in an animal model by using ΔFosB and cytochrome oxidase (COX) (immuno)histochemistry. The expression of these two markers of neuronal activity was analysed in the dentate nucleus (DN), interpositus nucleus (IN), and fastigial nucleus (FN) of the cerebellum of fully amygdala kindled rats that were sacrificed 48 hours after their last seizure. The DN and FN of kindled rats exhibited 25 to 29% less ΔFosB immunopositive cells than their respective counterpart in sham controls (P < 0.05). COX expression in the DN and FN of kindled animals was reduced by 32 to 33% compared to respective control values (P < 0.05). These results indicate that an epileptogenic state is characterized by decreased activity of deep cerebellar nuclei, especially the DN and FN. Possible consequences may include a decreased activation of the thalamus, contributing to further seizure spread. Restoration of FN activity by low frequency electrical stimulation is suggested as a possible treatment option in chronic epilepsy. PMID:26417599

  5. Idiopathic epilepsy and school achievement.

    PubMed

    Sturniolo, M G; Galletti, F

    1994-05-01

    Forty one children (20 boys, 21 girls) aged 6-10.8 years (mean age 8.6 years) who were affected with idiopathic epilepsy underwent neuropsychological (Wechsler Intelligence Scale for Children, Bender test) and behavioural assessment (Personality Inventory for Children; this was also used in a matched control group). Further information was obtained by teachers' reports. School underachievement occurred in 25 children (61%). Statistical analysis showed no influence of sex, social background, age of onset, seizure type, duration of illness, features seen on electroencephalography, and treatment. School failure was due to poor performance in almost all academic fields, and was associated with higher visuomotor impairment; children showing good school performance had a higher mean IQ and less visuomotor impairment. The behaviour of children with epilepsy who had a good academic performance did not differ from that of their healthy peers. Emotional maladjustment (social skill impairment, depression, poor motivation, and low self esteem) was associated with poor school performance. Such problems, that may complicate the course of idiopathic epilepsy and require an appropriate educational programme, should be carefully considered by the clinician. PMID:8017966

  6. How to Treat Compensated Absences.

    ERIC Educational Resources Information Center

    Lewandowski, Raymond J.

    1986-01-01

    Discusses compensated absences such as future vacation, sick leave, and other absences that must be recognized for accounting and financial reporting purposes. Explains Governmental Accounting Standards Board distinctions between governmental and proprietary fund models. School districts and municipalities must now account for compensated…

  7. International Bureau for Epilepsy survey of children, teenagers, and young people with epilepsy: data in China.

    PubMed

    Yu, Pei-Min; Ding, Ding; Zhu, Guo-Xing; Hong, Zhen

    2009-09-01

    The goals of this study were to assess the perception of people with or directly involved with childhood and adolescent epilepsy in China, and to gain insight into the real-life effects that epilepsy can have on quality of life, development, and opportunities for the future. Survey questionnaires were developed by the International Bureau for Epilepsy for three groups: teenagers and young adults, parents/caregivers of children with epilepsy, and health care professionals. In total we received 968 responses from 20 cities in China. Nearly two-thirds of teenagers and young adults with epilepsy (64.9%) and two-thirds of parents/caregivers of children with epilepsy (64.0%) who responded to the survey had kept epilepsy a secret from others. When asked specifically about drug-related side effects, more than half of teenagers and young adults with epilepsy reported experiencing side effects, specifically dizziness (23.9%), weight change (22.9%), and headache (14.5%). Health care professionals reported cognitive side effects (94.2%), mood change (56.7%), and skin rash (50%) in their patients with epilepsy. More than two-thirds of the teenagers and young adults with epilepsy (75.7%) expected the condition to hinder their lives in the future, affecting their chances of getting a job (52.6%), continuing their education (35.5%), and getting a boyfriend or girlfriend (33.7%). Among parents/caregivers of children with epilepsy, 85.7% expected the condition to hinder their child's life in the future. This survey documents some of the real-life consequences of epilepsy and highlights the important challenges and issues faced by people with epilepsy and their families in China. Ensuring that people are as free from seizures as possible and minimizing the side effects of treatment must be the primary goals of epilepsy management. PMID:19625221

  8. Anxiety in adolescent epilepsy. A clinimetric analysis.

    PubMed

    Carrozzino, Danilo; Marchetti, Daniela; Laino, Daniela; Minna, Maria; Verrocchio, Maria Cristina; Fulcheri, Mario; Verrotti, Alberto; Bech, Per

    2016-08-01

    Background Anxiety and depression have been considered to be neglected disorders in epilepsy. Because panic disorder is one of the most important anxiety disorders, it has been problematic to use very comprehensive anxiety questionnaires in epilepsy patients, as panic attacks and epileptic seizures, although two distinct clinical entities from a diagnostic point of view, show a significant overlap of symptoms. Aims We have focused on single items for anxiety and depression as screening candidates in adolescent epilepsy. Methods The individual panic attack item in the Screen for Children Anxiety Related Emotional Disorders Scale (SCARED) and the single depression item in the Kellner Symptom Questionnaire were tested. Our samples consisted of adolescent patients with epilepsy and a matched control group with healthy participants, as well as two numerical groups acting as controls. Results The single panic attack item identified panic anxiety in 24.1% in the group of patients with epilepsy and 0.0% in the matched control group (p = 0.01). The single depression item identified 52.2% with depression in the epilepsy group and 6.2% in the matched control group (p = 0.001). Conclusion As screening instruments, single items of panic attack and depression are sufficient to screen for these affective states in adolescent epilepsy. The clinical implications are that it is important to be quite specific when screening for depression and panic attacks in adolescent patients with epilepsy. PMID:26906494

  9. Spectrum of neurosurgeon's role in epilepsy surgery.

    PubMed

    Son, Eun-Ik; Kim, Ji-Eun

    2016-06-01

    It is well known that there is high quality evidence of epilepsy surgery as an effective and safe option for patients with drug refractory epilepsy by advanced imaging technology and computerized electrophysiological facilities during recent three decades. However, it still remains debate regarding necessities of epilepsy surgery in terms of less satisfactory surgical outcome, especially in non-lesional neocortical epilepsies. This review is for the role of epileptic neurosurgeon rather than the role of epilepsy surgery, namely, the necessity of neurosurgeon's positive participation starting from the first visit of epilepsy patients followed by pertaining process by stages and its degree of contribution. All experienced epilepsy centers also need innovative or challenging trial absolutely through this kind of standpoint, because all of the present protocols and techniques are coming from the past. In any event, the interdepartmental and interpersonal cooperation is inevitable especially for improving patient's quality of life. Serious neurosurgical considerations are needed for patients with intractable epilepsies, especially in referred cases from other center for the purpose of double check, and incongruent cases with contrary opinions by epileptologist. PMID:27621118

  10. Epilepsy and Intellectual and Developmental Disabilities

    ERIC Educational Resources Information Center

    Oguni, Hirokazu

    2013-01-01

    The co-occurrence of epilepsy in people with intellectual disabilities (ID) and other developmental disabilities (DD) has received attention because it has a significant negative impact on health, well-being, and quality of life. The current research investigating the frequency and form of epilepsy in children with ID and DD is reviewed, with…

  11. Living with Epilepsy--Not around It

    ERIC Educational Resources Information Center

    Apel, Laura

    2008-01-01

    This article presents an interview on Kevin Eggers, a 19-year-old college student from Seattle, Washington, who was diagnosed with epilepsy but had not let it prevent him from accomplishing his goals. As an Epilepsy Advocate, Kevin helps other teens and young adults realize that having a disability does not mean not living a normal and fulfilling…

  12. Pragmatic Communication Deficits in Children with Epilepsy

    ERIC Educational Resources Information Center

    Broeders, Mark; Geurts, Hilde; Jennekens-Schinkel, Aag

    2010-01-01

    Background: Various psychiatric and neurological disorders including epilepsy have been associated with language deficits. Pragmatic language deficits, however, have seldom been the focus of earlier studies in children with epilepsy. Moreover, it is unknown whether these pragmatic deficits are related to general intellectual functioning. Both…

  13. The representation of epilepsy in popular music.

    PubMed

    Baxendale, Sallie

    2008-01-01

    Much can be learned about the contemporary stereotypes associated with epilepsy by studying the representation of the disorder in paintings, literature, and movies. Popular music is arguably the most accessible and ubiquitous of the creative art forms, touching most of us on a daily basis. Reviewed here are the ways in which epilepsy and seizures are used in the lyrics of musicians from a wide variety of musical genres, from hip-hop to rhythm and blues. Many of the ancient associations of epilepsy with madness, horror, and lunacy can be found in these lyrics. However, the language of epilepsy has also been appropriated by some musical artists to represent a state of sexual ecstasy and dance euphoria. The references to these states as "epilepsy" or a "seizure" in numerous songs suggest that this shorthand is widely recognized within some subcultures. Although epilepsy has frequently been associated with female sexual availability in other creative art forms, this novel use of the language of epilepsy represents a contemporary departure in the artistic application of epilepsy-related images and associations in the 21st century. PMID:17980673

  14. The Treatment of Epilepsy in Autism.

    ERIC Educational Resources Information Center

    Gillberg, Christopher

    1991-01-01

    Sixty-six patients under age 25 with autism and epileptic seizures were treated and followed for 2 years. The cases are analyzed in terms of type of epilepsy, drugs used, and other treatments given. Practical guidelines are offered for the management of epilepsy in autism. (Author/JDD)

  15. Serotonin in Autism and Pediatric Epilepsies

    ERIC Educational Resources Information Center

    Chugani, Diane C.

    2004-01-01

    Serotonergic abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development--and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This…

  16. Pharmacotherapy of epilepsy: newly approved and developmental agents.

    PubMed

    Stephen, Linda J; Brodie, Martin J

    2011-02-01

    This article discusses seven newly available antiepileptic drugs (AEDs) and agents in phase III development. Lacosamide, licensed as an adjunctive treatment for partial-onset seizures, primarily acts by enhancing sodium channel slow inactivation. At daily doses of 200-600 mg, the drug significantly reduced partial-onset seizures in adults with refractory epilepsy. The most common adverse effects are CNS related. Rufinamide, available as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome, has an unclear mechanism of action, although it does block voltage-dependent sodium channels. Coadministration of valproic acid significantly increases rufinamide circulating concentrations. The drug has been shown to have efficacy for partial-onset, primary generalized tonic-clonic, tonic-atonic, absence and atypical absence seizures. Adverse effects are mainly somnolence, nausea and vomiting. Eslicarbazepine acetate, a carbamazepine analogue, was recently licensed as adjunctive treatment for partial-onset seizures. Eslicarbazepine acetate acts at voltage-gated sodium channels, although the precise mechanism of action is unclear. The drug had efficacy for partial-onset seizures in three randomized, double-blind, placebo-controlled studies, using 400, 800 or 1200 mg/day. Adverse effects include dizziness and somnolence. Retigabine (ezogabine) exerts its anticonvulsant effect through the opening of neuronal voltage-gated potassium channels. Following significant seizure reduction rates at dosages of 600, 900 and 1200 mg/day, license applications have been submitted for its use as adjunctive treatment for patients with partial-onset seizures. Dose-related adverse effects include somnolence, confusion and dizziness. Brivaracetam is the n-propyl analogue of levetiracetam. Mixed results have been obtained in phase III studies in patients with partial-onset seizures, and further trials in children, patients with photosensitive epilepsy and patients with partial

  17. Increased stathmin expression strengthens fear conditioning in epileptic rats.

    PubMed

    Zhang, Linna; Feng, Danni; Tao, Hong; DE, Xiangyan; Chang, Qing; Hu, Qikuan

    2015-01-01

    Patients with temporal lobe epilepsy have inexplicable fear attack as the aura. However, the underlying neural mechanisms of seizure-modulated fear are not clarified. Recent studies identified stathmin as one of the key controlling molecules in learning and innate fear. Stathmin binds to tubulin, inhibits microtubule assembly and promotes microtubule catastrophes. Therefore, stathmin is predicted to play a crucial role in the association of epilepsy seizures with fear conditioning. Firstly, a pilocarpine model of epilepsy in rats was established, and subsequently the fear condition training was performed. The epileptic rats with fear conditioning (epilepsy + fear) had a much longer freezing time compared to each single stimulus. The increased freezing levels revealed a significantly strengthened effect of the epileptic seizures on the learned fear of the tone-shock contextual. Subsequently, the stathmin expression was compared in the hippocampus, the amygdale, the insular cortex and the temporal lobe. The significant change of stathmin expression occurred in the insular and the hippocampus, but not in the amygdale. Stathmin expression and dendritic microtubule stability were compared between fear and epilepsy in rats. Epilepsy was found to strengthen the fear conditioning with increased expression of stathmin and a decrease in microtubule stability. Fear conditioning slightly increased the expression of stathmin, whereas epilepsy with fear conditioning increased it significantly in the hippocampus, insular cortex and hypothalamus. The phosphorylated stathmin slightly increased in the epilepsy with fear conditioning. The increased expression of stathmin was contrary to the decrease of the stathmin microtubule-associated protein (MAP2) and α-tubulin in the epileptic rats with fear conditioning in all three areas of the brain. The most significant change of the ratio of MAP2 and α-tubulin/stathmin occurred in the insular cortex and hippocampus. In conclusion

  18. Altered expression of the voltage-gated calcium channel subunit α2δ-1: A comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain

    PubMed Central

    Nieto-Rostro, M.; Sandhu, G.; Bauer, C.S.; Jiruska, P.; Jefferys, J.G.R.; Dolphin, A.C.

    2014-01-01

    The auxiliary α2δ-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The α2δ-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, α2δ-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of α2δ-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of α2δ-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of α2δ-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganization of α2δ-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining. PMID:24641886

  19. Epidemiology of epilepsy in developing countries.

    PubMed Central

    Senanayake, N.; Román, G. C.

    1993-01-01

    Epilepsy is an important health problem in developing countries, where its prevalence can be up to 57 per 1000 population. This article reviews the epidemiology of epilepsy in developing countries in terms of its incidence, prevalence, seizure type, mortality data, and etiological factors. The prevalence of epilepsy is particularly high in Latin America and in several African countries, notably Liberia, Nigeria, and the United Republic of Tanzania. Parasitic infections, particularly neurocysticercosis, are important etiological factors for epilepsy in many of these countries. Other reasons for the high prevalence include intracranial infections of bacterial or viral origin, perinatal brain damage, head injuries, toxic agents, and hereditary factors. Many of these factors are, however, preventable or modifiable, and the introduction of appropriate measures to achieve this could lead to a substantial decrease in the incidence of epilepsy in developing countries. PMID:8490989

  20. [Vitamin-responsive epilepsies: an update].

    PubMed

    Tabarki, B; Thabet, F

    2013-11-01

    Inborn error of metabolism may produce a complex clinical picture in which epilepsy is only one of the various neurologic manifestations including developmental delay/regression, mental retardation, and movement disorders. However, metabolic epilepsies may dominate the clinical presentation. A specific diagnosis of metabolic disorders in epileptic patients may provide the possibility of specific treatments that can improve seizures. In a few metabolic diseases such as vitamin-responsive epilepsies, epilepsy responds to specific treatments based on supplementation of cofactors. Certain rare vitamin-responsive inborn errors of metabolism may present as early encephalopathy with anticonvulsant-resistant seizures. These include pyridoxine-dependent seizures, pyridoxal-phosphate-dependent seizures, folinic acid-responsive seizures, and biotinidase deficiency. This review discusses our current understanding of these vitamin-responsive epilepsies. PMID:24080039

  1. Obtaining genetic testing in pediatric epilepsy.

    PubMed

    Ream, Margie A; Patel, Anup D

    2015-10-01

    The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy. PMID:26345167

  2. Anxiety disorders in people with epilepsy.

    PubMed

    Brandt, Christian; Mula, Marco

    2016-06-01

    Anxiety disorders are frequent, though probably underdiagnosed, comorbidities in epilepsy. Epilepsy and anxiety may share common neurobiological correlates as shown in animal models and suggested by studies demonstrating anxiety disorders before the manifestation of epilepsy. Comorbid anxiety disorders have a major impact on the affected patients' quality of life and may increase the risk for suicidality. Successful treatment of the epilepsy may alleviate anxiety symptoms. Treatment of anxiety is based on selective serotonin reuptake inhibitors, benzodiazepines (although only as second-line choices), and psychotherapy. Specific AEDs (especially pregabalin) have been shown to have anxiolytic properties. This paper is aimed at reviewing anxiety disorders in patients with epilepsy discussing current scientific evidence about pathophysiology, clinical aspects, and treatment strategies. PMID:27116536

  3. Benign idiopathic partial epilepsy and brain lesion.

    PubMed

    Stephani, U; Doose, H

    1999-03-01

    A 14-year-old girl had severe head trauma from a dog bite at the age of 9 days. This resulted in extensive brain damage, tetraplegia, mental retardation, and epilepsy. The seizures were of rolandic type, and the EEG showed multifocal sharp waves. The course was benign. The initial diagnosis of a pure symptomatic epilepsy was revised after demonstrating typical benign focal sharp waves in the EEG of the healthy sister. Thus a phenocopy of a benign partial epilepsy by the brain lesion could be excluded with sufficient certainty. This observation allows the conclusion that the genetic disposition underlying the sharp-wave trait characteristic of benign partial epilepsies can be involved also in the pathogenesis of seemingly pure symptomatic epilepsies. EEG studies on siblings of such patients are needed to exclude possible phenocopies. PMID:10080522

  4. Optimization of epilepsy treatment with vagus nerve stimulation

    NASA Astrophysics Data System (ADS)

    Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges

    2007-11-01

    Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the

  5. From classification to epilepsy ontology and informatics.

    PubMed

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

    2012-07-01

    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. Multidimensionality 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 National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) Common Data Elements, the International Classification of Diseases (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 multimodal 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

  6. 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

  7. Epilepsy and seizure ontology: towards an epilepsy informatics infrastructure for clinical research and patient care

    PubMed Central

    Sahoo, Satya S; Lhatoo, Samden D; Gupta, Deepak K; Cui, Licong; Zhao, Meng; Jayapandian, Catherine; Bozorgi, Alireza; Zhang, Guo-Qiang

    2014-01-01

    Objective Epilepsy encompasses an extensive array of clinical and research subdomains, many of which emphasize multi-modal physiological measurements such as electroencephalography and neuroimaging. The integration of structured, unstructured, and signal data into a coherent structure for patient care as well as clinical research requires an effective informatics infrastructure that is underpinned by a formal domain ontology. Methods We have developed an epilepsy and seizure ontology (EpSO) using a four-dimensional epilepsy classification system that integrates the latest International League Against Epilepsy terminology recommendations and National Institute of Neurological Disorders and Stroke (NINDS) common data elements. It imports concepts from existing ontologies, including the Neural ElectroMagnetic Ontologies, and uses formal concept analysis to create a taxonomy of epilepsy syndromes based on their seizure semiology and anatomical location. Results EpSO is used in a suite of informatics tools for (a) patient data entry, (b) epilepsy focused clinical free text processing, and (c) patient cohort identification as part of the multi-center NINDS-funded study on sudden unexpected death in epilepsy. EpSO is available for download at http://prism.case.edu/prism/index.php/EpilepsyOntology. Discussion An epilepsy ontology consortium is being created for community-driven extension, review, and adoption of EpSO. We are in the process of submitting EpSO to the BioPortal repository. Conclusions EpSO plays a critical role in informatics tools for epilepsy patient care and multi-center clinical research. PMID:23686934

  8. Interictal mood and personality disorders in temporal lobe epilepsy and juvenile myoclonic epilepsy.

    PubMed Central

    Perini, G I; Tosin, C; Carraro, C; Bernasconi, G; Canevini, M P; Canger, R; Pellegrini, A; Testa, G

    1996-01-01

    BACKGROUND: Mood disorders have been described as the commonest psychiatric disorders in patients with temporal lobe epilepsy. Secondary depression in temporal lobe epilepsy could be interpreted either as an adjustment reaction to a chronic disease or as a limbic dysfunction. To clarify this issue, a controlled study of psychiatric disorders was conducted in different forms of epileptic and non-epileptic chronic conditions. METHODS: Twenty outpatients with temporal lobe epilepsy, 18 outpatients with juvenile myoclonic epilepsy--a primary generalised seizure disorder--20 matched type I diabetic patients, and 20 matched normal controls were assessed by a structured interview (SADS) and by self rating scales (Beck depression inventory (BDI) and the state and trait anxiety scales STAIX1 and STAIX2). RESULTS: Sixteen (80%) patients with temporal lobe epilepsy fulfilled the criteria for a psychiatric diagnosis at the SADS interview with a significantly higher frequency than patients with juvenile myoclonic epilepsy (22%) and diabetic patients (10%) (P < 0.0001). The most frequent disorder in temporal lobe epilepsy was a mood disorder: 11 (55%) patients with temporal lobe epilepsy had depression compared with three patients with juvenile myoclonic epilepsy and two diabetic patients (P < 0.001). Eight patients with temporal lobe epilepsy with an affective disorder also had a comorbid personality or anxiety disorder. Patients with temporal lobe epilepsy scored significantly higher on BDI, STAIX1, and STAIX2 than the three control groups (P < 0.001, P < 0.01, P < 0.001). CONCLUSIONS: Patients with temporal lobe epilepsy have a higher incidence of affective and personality disorders, often in comorbidity, than patients with juvenile myoclonic epilepsy and diabetic patients suggesting that these psychiatric disorders are not an adjustment reaction to a chronic disease but rather reflect a limbic dysfunction. PMID:8971108

  9. Electroencephalography as a tool for evidence-based diagnosis and improved outcomes in children with epilepsy in a resource-poor setting

    PubMed Central

    Lagunju, Ike Oluwa Abiola; Oyinlade, Alexander Opebiyi; Atalabi, Omolola Mojisola; Ogbole, Godwin; Tedimola, Olushola; Famosaya, Abimbola; Ogunniyi, Adesola; Ogunseyinde, Ayotunde Oluremi; Ragin, Ann

    2015-01-01

    Introduction Electroencephalography (EEG) remains the most important investigative modality in the diagnostic evaluation of individuals with epilepsy. Children living with epilepsy in the developing world are faced with challenges of lack of access to appropriate diagnostic evaluation and a high risk of misdiagnosis and inappropriate therapy. We appraised EEG studies in a cohort of Nigerian children with epilepsy seen in a tertiary center in order to evaluate access to and the impact of EEG in the diagnostic evaluation of the cases. Methods Inter-ictal EEG was requested in all cases of pediatric epilepsy seen at the pediatric neurology clinic of the University College Hospital, Ibadan, Nigeria over a period of 18 months. Clinical diagnosis without EEG evaluation was compared with the final diagnosis post- EEG evaluation. Results A total of 329 EEGs were recorded in 329 children, aged 3months to 16 years, median 61.0 months. Clinical evaluation pre-EEG classified 69.3% of the epilepsies as generalized. The a posteriori EEG evaluations showed a considerably higher proportion of localization-related epilepsies (33.6%). The final evaluation post EEG showed a 21% reduction in the proportion of cases labeled as generalized epilepsy and a 55% increase in cases of localization-related epilepsy(p<0.001). Conclusion Here we show that there is a high risk of misdiagnosis and therefore the use of inappropriate therapies in children with epilepsy in the absence of EEG evaluation. The implications of our findings in the resource-poor country scenario are key for reducing the burden of care and cost of epilepsy treatment on both the caregivers and the already overloaded tertiary care services. PMID:26977236

  10. Issues for Women with Epilepsy.

    PubMed

    Vélez-Ruiz, Naymeé J; Pennell, Page B

    2016-05-01

    Epilepsy and antiepileptic drugs affect the menstrual cycle, aspects of contraception, reproductive health, pregnancy, and menopause through alteration of sex steroid hormone pathways. Sex steroid hormones often have an effect on seizure frequency and may alter the level of some antiepileptic drugs. Approximately one-third of women experience an increase in perimenstrual and/or periovulatory seizure frequency. Some women experience an increase in seizure frequency during pregnancy. Balancing maternal seizure control and the risk of congenital malformations associated with fetal antiepileptic drug exposure may be challenging. Some antiepileptic drugs are associated with cognitive and behavioral teratogenesis and should be avoided if possible during pregnancy. PMID:27086987

  11. A New Approach for Epilepsy.

    PubMed

    Dingledine, Ray; Hassel, Bjørnar

    2016-01-01

    About one-third of the 65 million people worldwide affected by epilepsy are treatment-resistant, and the degree to which they suffer from seizures and convulsions can vary widely. Problems occur when nerve cells in the brain fail to communicate properly. A new study has found that inhibiting an enzyme that is critical in metabolic communication has an anti-seizure effect in epileptic mice. These findings, the authors believe, may very well initiate a shift to new therapeutic approaches. PMID:27408679

  12. Epilepsy emergencies: diagnosis and management.

    PubMed

    Foreman, Brandon; Hirsch, Lawrence J

    2012-02-01

    Seizures and status epilepticus are epilepsy emergencies with high morbidity and mortality. Early treatment is crucial, and the identification of an underlying etiology informs both continued treatment and prognosis. Many patients have underdiagnosed nonconvulsive seizures or nonconvulsive status epilepticus, particularly the comatose or critically ill. Timely EEG can be useful for diagnosis, management, optimizing treatment response, and determining prognosis in these patients. Refractory conditions can be quite complicated with limited evidence-based guidance, but treatment should not be restricted by nihilism even in the most prolonged cases, especially if there is not widespread irreversible brain injury. PMID:22284053

  13. The social competence and behavioral problem substrate of new- and recent-onset childhood epilepsy

    PubMed Central

    Almane, Dace; Jones, Jana E.; Jackson, Daren C.; Seidenberg, Michael; Hermann, Bruce P.

    2014-01-01

    This study examined patterns of syndrome-specific problems in behavior and competence in children with new-or recent-onset epilepsy compared with healthy controls. Research participants consisted of 205 children aged 8–18, including youth with recent-onset epilepsy (n = 125, 64 localization-related epilepsy [LRE] and 61 idiopathic generalized epilepsy [IGE]) and healthy first-degree cousin controls (n = 80). Parents completed the Child Behavior Checklist for children aged 6–18 (CBCL/6–18) from the Achenbach System of Empirically Based Assessment (ASEBA). Dependent variables included Total Competence, Total Problems, Total Internalizing, Total Externalizing, and Other Problems scales. Comparisons of children with LRE and IGE with healthy controls were examined followed by comparisons of healthy controls with those having specific epilepsy syndromes of LRE (BECTS, Frontal/Temporal Lobe, and Focal NOS) and IGE (Absence, Juvenile Myoclonic, and IGE NOS). Children with LRE and/or IGE differed significantly (p < 0.05) from healthy controls, but did not differ from each other, across measures of behavior (Total Problems, Total Internalizing, Total Externalizing, and Other Problems including Thought and Attention Problems) or competence (Total Competence including School and Social). Similarly, children with specific syndromes of LRE and IGE differed significantly (p < 0.05) from controls across measures of behavior (Total Problems, Total Internalizing, and Other Problems including Attention Problems) and competence (Total Competence including School). Only on the Thought Problems scale were there syndrome differences. In conclusion, children with recent-onset epilepsy present with significant behavioral problems and lower competence compared with controls, with little syndrome specificity whether defined broadly (LRE and IGE) or narrowly (specific syndromes of LRE and IGE). PMID:24374977

  14. Parental psychopathology and self-rated quality of life in adolescents with epilepsy in Nigeria.

    PubMed

    Adewuya, Abiodun O

    2006-07-01

    This study sought to investigate the relationship between parental psychopathology and health-related quality of life in a group of Nigerian adolescents with epilepsy. The participants were 86 adolescents with epilepsy (50 males, 36 females; mean age 14y 5mo [SD 2y 1mo]; age range 12-18y). There were 54 (62.8%) adolescents with complex partial seizures, six (7.0%) with simple partial seizures, 14 (16.3%) with generalized tonic-clonic seizures, four (4.7%) with absence seizures, and eight (9.2%) with other types of seizure. They completed the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48). Parents also completed the General Health Questionnaire, Zung's Self-Rating Anxiety Scale, and Zung's Self-Rating Depressive Scale as measures of their psychopathology. Factors correlating with poor overall quality of life in the adolescents include longer duration of illness, large number of antiepileptic drugs, more severe medication toxicity, and psychopathology in the parents. General psychopathology in parents is significantly associated with QOLIE-AD-48 subscales of Epilepsy Impact (r=0.527, p<0.001), Attitude (r=0.214, p=0.047), Physical Function (r=0.417, p<0.001), Stigma (r=0.305, p=0.004), Social Support (r=0.365, p=0.001), and School Behaviour (r=0.220, p=0.042). There is a possibility of a cross-cultural difference on the effect of epilepsy on the quality of life of adolescents. Psychopathology in parents is significantly associated with poorer quality of life of these adolescents. Physicians should consider this, therefore, when planning intervention strategies in improving the quality of life in adolescents with epilepsy. PMID:16780631

  15. A prospective study of the modified Atkins diet for adults with idiopathic generalized epilepsy.

    PubMed

    Kverneland, Magnhild; Selmer, Kaja K; Nakken, Karl O; Iversen, Per O; Taubøll, Erik

    2015-12-01

    For children with pharmacoresistant epilepsy, the ketogenic diet is an established treatment option worldwide. However, for adults, this treatment is less frequently offered, and its efficacy less well-documented. The aim of this study was to examine efficacy and tolerability of such a diet as an adjuvant therapy to antiepileptic drugs for adult patients with pharmacoresistant generalized epilepsy. Thirteen patients (12 women) aged 16-57 years were included prospectively. They were treated with a modified Atkins diet for 12 weeks. Nine of the 13 participants had juvenile myoclonic epilepsy (JME), two had childhood absence epilepsy, one had Jeavons syndrome, and one had generalized epilepsy of unknown type. Six participants, all with JME, completed the 12-week study period. Among these six, four had >50% seizure reduction. Their seizure severity, using the revised Liverpool Seizure Severity Scale, was reduced by 1, 5, 57.5, and 70 points, respectively (scale: 1-100 points). In three of these four responders, quality of life, assessed by QOLIE-89, increased more than 20 points (scale: 0-100 points). Mean reduction of body weight after 12 weeks on diet was 6.5 (range: 4.3-8.1) kg. Lack of motivation, poor compliance, and seizure aggravation were the main reasons for premature termination of the diet. Apart from one patient who developed gallstones when ending the treatment after 10 months, no adverse effects were noted. In conclusion, using a modified Atkins diet for 12 weeks led to a clinically relevant reduction of seizure frequency in four of thirteen adult patients with pharmacoresistant generalized epilepsy. All responders were diagnosed with JME. In three of the four, the benefits of diet were so considerable that they chose to continue the treatment. PMID:26588588

  16. Musical and poetic creativity and epilepsy.

    PubMed

    Hesdorffer, Dale C; Trimble, Michael

    2016-04-01

    Associations between epilepsy and musical or poetic composition have received little attention. We reviewed the literature on links between poetic and musical skills and epilepsy, limiting this to the Western canon. While several composers were said to have had epilepsy, John Hughes concluded that none of the major classical composers thought to have had epilepsy actually had it. The only composer with epilepsy that we could find was the contemporary composer, Hikari Oe, who has autism and developed epilepsy at age 15years. In his childhood years, his mother found that he had an ability to identify bird sound and keys of songs and began teaching him piano. Hikari is able to compose in his head when his seizures are not severe, but when his seizures worsen, his creativity is lost. Music critics have commented on the simplicity of his musical composition and its monotonous sound. Our failure to find evidence of musical composers with epilepsy finds parallels with poetry where there are virtually no established poets with epilepsy. Those with seizures include Lord George Byron in the setting of terminal illness, Algernon Swinburne who had alcohol-related seizures, Charles Lloyd who had seizures and psychosis, Edward Lear who had childhood onset seizures, and Vachel Lindsay. The possibility that Emily Dickinson had epilepsy is also discussed. It has not been possible to identify great talents with epilepsy who excel in poetic or musical composition. There are few published poets with epilepsy and no great composers. Why is this? Similarities between music and poetry include meter, tone, stress, rhythm, and form, and much poetry is sung with music. It is likely that great musical and poetic compositions demand a greater degree of concentration and memory than is possible in epilepsy, resulting in problems retaining a musical and mathematical structure over time. The lack of association between recognizable neuropsychiatric disorders and these skills is a gateway to

  17. Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.

    PubMed

    Baulac, Michel; de Boer, Hanneke; Elger, Christian; Glynn, Mike; Kälviäinen, Reetta; Little, Ann; Mifsud, Janet; Perucca, Emilio; Pitkänen, Asla; Ryvlin, Philippe

    2015-11-01

    The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in

  18. Single-Gene Determinants of Epilepsy Comorbidity.

    PubMed

    Noebels, Jeffrey L

    2015-11-01

    Common somatic conditions are bound to occur by chance in individuals with neurological disorders as prevalent as epilepsy, but when biological links underlying the comorbidity can be uncovered, the relationship may provide clues into the origin and mechanisms of both. The expanding list of monogenic epilepsies and their associated clinical features offer a remarkable opportunity to mine the epilepsy genome for coordinate neurodevelopmental phenotypes and examine their pathogenic mechanisms. Defined single-gene-linked epilepsy syndromes identified to date include all of the most frequently cited comorbidities, such as cognitive disorders, autism, migraine, mood disorders, late-onset dementia, and even premature lethality. Gene-linked comorbidities may be aggravated by, or independent of, seizure history. Mutations in these genes establish clear biological links between abnormal neuronal synchronization and a variety of neurobehavioral disorders, and critically substantiate the definition of epilepsy as a complex spectrum disorder. Mapping the neural circuitry of epilepsy comorbidities and understanding their single-gene risk should substantially clarify this challenging aspect of clinical epilepsy management. PMID:26525453

  19. Clinical approach to posttraumatic epilepsy.

    PubMed

    Rao, Vikram R; Parko, Karen L

    2015-02-01

    Traumatic brain injury (TBI) is one of the most common causes of acquired epilepsy, and posttraumatic epilepsy (PTE) results in significant somatic and psychosocial morbidity. The risk of developing PTE relates directly to TBI severity, but the latency to first seizure can be decades after the inciting trauma. Given this "silent period," much work has focused on identification of molecular and radiographic biomarkers for risk stratification and on development of therapies to prevent epileptogenesis. Clinical management requires vigilant neurologic surveillance and recognition of the heterogeneous endophenotypes associated with PTE. Appropriate treatment of patients who have or are at risk for seizures varies as a function of time after TBI, and the clinician's armamentarium includes an ever-expanding diversity of pharmacological and surgical options. Most recently, neuromodulation with implantable devices has emerged as a promising therapeutic strategy for some patients with refractory PTE. Here, we review the epidemiology, diagnostic considerations, and treatment options for PTE and develop a roadmap for providers encountering this challenging clinical entity. PMID:25714868

  20. Epilepsy in pregnancy: best evidence for care.

    PubMed

    Ruth, Donna Jean; Barnett, James

    2013-01-01

    Epilepsy is the most commonly encountered neurologic disorder during pregnancy. A majority of women with epilepsy continue antiepileptic drug regimens during pregnancy. To provide evidence-based care to women with epilepsy, it is critical that healthcare providers possess a basic knowledge of seizures, antiepileptic medications, and interventions specific to this patient population, as well as an understanding of the patient's basic needs and concerns. This article provides a discussion of seizure types, common antiepileptic medications, and provides evidence-based interventions related to the fetus and the mother during preconception, intrapartum, and postpartum periods. PMID:23899800

  1. [Quality of life in childhood epilepsy].

    PubMed

    Herranz, J L; Casas, C

    1996-01-01

    We describe a Quality Life scale in childhood epilepsy (CAVE) composed by 8 items, behaviour, school compliance, learning, autonomy, social relation, frequency and intensity of seizures and the parents opinions. Each item may be answered as very bad (5), bad (2), medium (3), good (4), or very good (5), and we can obtain full scores before and after the beginning of epileptic treatment and we can compare them. Although other Quality Life questionnaires exist for adult epilepsy, CAVE is the first scale applied for chronic childhood epilepsy. PMID:8851997

  2. Role of Sodium Channels in Epilepsy.

    PubMed

    Kaplan, David I; Isom, Lori L; Petrou, Steven

    2016-01-01

    Voltage-gated sodium channels (VGSCs) are fundamentally important for the generation and coordinated transmission of action potentials throughout the nervous system. It is, therefore, unsurprising that they have been shown to play a central role in the genesis and alleviation of epilepsy. Genetic studies on patients with epilepsy have identified more than 700 mutations among the genes that encode for VGSCs attesting to their role in pathogenesis. Further, many common antiepileptic drugs act on VGSCs to suppress seizure activity. Here, we present an account of the role of VGSCs in epilepsy, both through their pathogenic dysfunction and as targets for pharmacotherapy. PMID:27143702

  3. Teachers' knowledge about epilepsy and attitudes toward students with epilepsy: results of a national survey.

    PubMed

    Bishop, Malachy; Boag, Emily M

    2006-03-01

    The attitudes and epilepsy-related knowledge of teachers are an important component of the educational experiences of children with epilepsy. Unfortunately however, the exploration of teacher attitudes and knowledge has been extremely limited in the United States. This article describes a survey-based research study of the attitudes and epilepsy-related knowledge of a randomly selected national sample of 512 elementary and middle school teachers in the United States. The questionnaire included the Scale of Attitudes Toward Persons with Epilepsy (ATPE), a summated rating scale that measures both attitudes toward persons with epilepsy and knowledge about epilepsy, as well as a demographic and teaching experience survey and several additional attitude and knowledge items developed by the researchers. The results suggest that although teachers' attitudes about epilepsy were generally positive, there were significant deficits in terms of general knowledge about epilepsy, its impact in educational settings, and the appropriate management of epilepsy and seizures in the classroom. Critical areas in which to focus remedial education and outreach efforts are identified. PMID:16406818

  4. [Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version].

    PubMed

    Rosenow, F; Bast, T; Czech, T; Hans, V; Helmstaedter, C; Huppertz, H-J; Seeck, M; Trinka, E; Wagner, K

    2014-06-01

    In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory. PMID:24861193

  5. International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals.

    PubMed

    Berendt, Mette; Farquhar, Robyn G; Mandigers, Paul J J; Pakozdy, Akos; Bhatti, Sofie F M; De Risio, Luisa; Fischer, Andrea; Long, Sam; Matiasek, Kaspar; Muñana, Karen; Patterson, Edward E; Penderis, Jacques; Platt, Simon; Podell, Michael; Potschka, Heidrun; Pumarola, Martí Batlle; Rusbridge, Clare; Stein, Veronika M; Tipold, Andrea; Volk, Holger A

    2015-01-01

    Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, "a common language", for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders. PMID:26316133

  6. Genetic etiology of new forms of familial epilepsy.

    PubMed

    Wang, Xuefeng; Lu, Yang

    2008-01-01

    Epilepsy is a common neurological disorder with an incidence of approximately 0.5%. In order to develop better strategies for treatment of epilepsy, more insight on the etiology and pathogenesis of epilepsy is required. In 2001, based on the diagnostic scheme of the International League Against Epilepsy, three new forms of familial epilepsy were identified. These include familial temporal lobe epilepsy, familial focal epilepsy with variable foci, and generalized epilepsy with febrile seizure plus. Mutation of a distinct set of genes has been reported in several forms of epilepsy. Mutation of LGI1 gene has been identified in familial lateral temporal lobe epilepsy while mutations of genes which encode sodium channels and GABAA receptors have been reported in generalized epilepsy with febrile seizure plus. However, no disease-causing gene has yet been found in families with familial mesial temporal lobe epilepsy or those with familial focal epilepsy with variable foci. Here, we review the genetic background of these three familial epilepsy syndromes, and provide a better insight on their genetic etiology. PMID:17981785

  7. Social competence in pediatric epilepsy: insights into underlying mechanisms.

    PubMed

    Caplan, Rochelle; Sagun, Jaclyn; Siddarth, Prabha; Gurbani, Suresh; Koh, Susan; Gowrinathan, R; Sankar, Raman

    2005-03-01

    This study compared parent-based Child Behavior Checklist (CBCL) social competence scores of 90 children with complex partial seizures (CPS) and 62 with absence epilepsy (CAE) of average intelligence with scores of 91 healthy children. It also examined the role of seizure-related, cognitive, behavioral, linguistic, social communication, and demographic variables on these measures. When differences in cognitive, linguistic, and demographic variables were controlled for, the CPS and CAE groups had significantly lower scores in the school, but not in the social interaction and activities domains compared with the healthy control group. Among the patients, lower Full Scale IQ externalizing behaviors, disruptive disorders, minority status, and impaired social communication, but not seizure variables, predicted lower social competence scores. These findings demonstrate the importance of controlling for cognitive, behavioral, and demographic variables in social competence studies of children with CPS and CAE and the need to assess cognition and behavior when parents report school and social problems in these children. PMID:15710308

  8. Magnetoencephalography in the study of epilepsy and consciousness.

    PubMed

    Foley, Elaine; Cerquiglini, Antonella; Cavanna, Andrea; Nakubulwa, Mable Angela; Furlong, Paul Lawrence; Witton, Caroline; Seri, Stefano

    2014-01-01

    The neural bases of altered consciousness in patients with epilepsy during seizures and at rest have raised significant interest in the last decade. This exponential growth has been supported by the parallel development of techniques and methods to investigate brain function noninvasively with unprecedented spatial and temporal resolution. In this article, we review the contribution of magnetoencephalography to deconvolve the bioelectrical changes associated with impaired consciousness during seizures. We use data collected from a patient with refractory absence seizures to discuss how spike-wave discharges are associated with perturbations in optimal connectivity within and between brain regions and discuss indirect evidence to suggest that this phenomenon might explain the cognitive deficits experienced during prolonged 3/s spike-wave discharges. PMID:24113567

  9. Opportunities for improving animal welfare in rodent models of epilepsy and seizures.

    PubMed

    Lidster, Katie; Jefferys, John G; Blümcke, Ingmar; Crunelli, Vincenzo; Flecknell, Paul; Frenguelli, Bruno G; Gray, William P; Kaminski, Rafal; Pitkänen, Asla; Ragan, Ian; Shah, Mala; Simonato, Michele; Trevelyan, Andrew; Volk, Holger; Walker, Matthew; Yates, Neil; Prescott, Mark J

    2016-02-15

    Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). PMID:26376175

  10. Absence status associated with focal activity and polydipsia-induced hyponatremia

    PubMed Central

    Azuma, Hideki; Akechi, Tatsuo; Furukawa, Toshi A

    2008-01-01

    We report a case of de novo absence status associated with focal discharge and polydipsia-induced hyponatremia. Nonconvulsive status epilepticus (NCSE) is classified as absence status or complex partial status. Absence status is characterized by bilateral synchronized spike and wave complex bursts and a variety of conscious disturbances. Possible precipitating factors for NCSE include benzodiazepine withdrawal, excessive use of psychotropic drugs, and electrolyte imbalances. Hyponatremia is a rare precipitating factor. In this case, the patient was 59 years old and had suffered from primary insomnia but had no history of epilepsy. NCSE improved by means of saline infusion. However after recovery from NCSE EEG revealed some spikes in the left frontal area. Absence seizures can also show generalized spike and slow waves, and cases of focal lesion-associated absence seizures have been reported. Although absence seizures and absence status are two distinct conditions, they should not be considered together. We assumed that hyponatremia induced by polydipsia precipitated epileptogenicity in the left frontal area, and then focal activity secondarily generalized and resulted in absence status. PMID:18728738

  11. Animal models of tumour-associated epilepsy.

    PubMed

    Kirschstein, Timo; Köhling, Rüdiger

    2016-02-15

    Brain tumours cause a sizeable proportion of epilepsies in adulthood, and actually can be etiologically responsible also for childhood epilepsies. Conversely, seizures are often first clinical signs of a brain tumour. Nevertheless, several issues of brain-tumour associated seizures and epilepsies are far from understood, or clarified regarding clinical consensus. These include both the specific mechanisms of epileptogenesis related to different tumour types, the possible relationship between malignancy and seizure emergence, the interaction between tumour mass and surrounding neuronal networks, and - not least - the best treatment options depending on different tumour types. To investigate these issues, experimental models of tumour-induced epilepsies are necessary. This review concentrates on the description of currently used models, focusing on methodological aspects. It highlights advantages and shortcomings of these models, and identifies future experimental challenges. PMID:26092434

  12. Prolonged partial epilepsy: a case report

    SciTech Connect

    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.

  13. Molecular basis of an inherited epilepsy.

    PubMed

    Lossin, Christoph; Wang, Dao W; Rhodes, Thomas H; Vanoye, Carlos G; George, Alfred L

    2002-06-13

    Epilepsy is a common neurological condition that reflects neuronal hyperexcitability arising from largely unknown cellular and molecular mechanisms. In generalized epilepsy with febrile seizures plus, an autosomal dominant epilepsy syndrome, mutations in three genes coding for voltage-gated sodium channel alpha or beta1 subunits (SCN1A, SCN2A, SCN1B) and one GABA receptor subunit gene (GABRG2) have been identified. Here, we characterize the functional effects of three mutations in the human neuronal sodium channel alpha subunit SCN1A by heterologous expression with its known accessory subunits, beta1 and beta2, in cultured mammalian cells. SCN1A mutations alter channel inactivation, resulting in persistent inward sodium current. This gain-of-function abnormality will likely enhance excitability of neuronal membranes by causing prolonged membrane depolarization, a plausible underlying biophysical mechanism responsible for this inherited human epilepsy. PMID:12086636

  14. Pathogenesis of Epilepsy: Challenges in Animal Models

    PubMed Central

    Hui Yin, Yow; Ahmad, Nurulumi; Makmor-Bakry, Mohd

    2013-01-01

    Epilepsy is one of the most common chronic disorders affecting individuals of all ages. A greater understanding of pathogenesis in epilepsy will likely provide the basis fundamental for development of new antiepileptic therapies that aim to prevent the epileptogenesis process or modify the progression of epilepsy in addition to treatment of epilepsy symptomatically. Therefore, several investigations have embarked on advancing knowledge of the mechanism underlying epileptogenesis, understanding in mechanism of pharmacoresistance and discovering antiepileptogenic or disease-modifying therapy. Animal models play a crucial and significant role in providing additional insight into mechanism of epileptogenesis. With the help of these models, epileptogenesis process has been demonstrated to be involved in various molecular and biological pathways or processes. Hence, this article will discuss the known and postulated mechanisms of epileptogenesis and challenges in using the animal models. PMID:24494063

  15. Seizures and Epilepsy: Hope through Research

    MedlinePlus

    ... narcolepsy that may look like epilepsy. A magnetoencephalogram (MEG) detects the magnetic signals generated by neurons to help detect surface abnormalities in brain activity. MEG can be used in planning a surgical strategy ...

  16. Mechanisms Responsible for Cognitive Impairment in Epilepsy.

    PubMed

    Lenck-Santini, Pierre-Pascal; Scott, Rodney C

    2015-10-01

    Epilepsy is often associated with cognitive and behavioral impairments that can have profound impact on the quality of life of patients. Although the mechanisms of cognitive impairment are not completely understood, we make an attempt to describe, from a systems perspective, how information processing is affected in epilepsy disorders. The aim of this review is to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contributions of etiology, seizures, and interictal discharges (IDs). We conclude that these mechanisms are likely to be important and deserve more detailed scrutiny in the future. PMID:26337111

  17. Flunarizine in therapy-resistant infantile epilepsies.

    PubMed

    Curatolo, P; Cusmai, R; Bruni, O; Pruna, D; Brindesi, I

    1986-01-01

    An open add-on trial with flunarizine has been carried out in 27 cases of therapy resistant infantile epilepsies: 15 partial and 12 generalized epilepsies. Etiology was an hypoxic-ischemic encephalopathy (HIE) in 13 cases, cerebral malformations in 10 cases and 4 various prenatal and perinatal cases. After a 2 months baseline period, flunarizine was given in addition to the previous therapy in a 5 mg once daily dose. A single blind versus placebo study was carried out in another series of 16 cases. Better results were found in HIE cases than in malformative cases, and in cases with perinatal HIE than in cases with prenatal hypoxic encephalopathy. The improvement in symptomatic generalized epilepsies was more evident than in symptomatic partial epilepsies. Drowsiness was the only side effect reported. PMID:3609883

  18. Autosomal dominant rolandic epilepsy with speech dyspraxia.

    PubMed

    Scheffer, I E

    2000-01-01

    Autosomal Dominant Rolandic Epilepsy with Speech Dyspraxia (ADRESD) is a rare disorder which highlights the relationship between Benign Rolandic Epilepsy (BRE) and speech and language disorders. Subtle speech and language disorders have recently been well characterised in BRE. ADRESD is associated with long term, more severe speech and language difficulties. The time course of rolandic epilepsy in ADRESD is typical of that of BRE. ADRESD is inherited in an autosomal dominant manner with anticipation. It is postulated that the anticipation may be due to an, as yet unidentified, triplet repeat expansion in a gene for rolandic epilepsy. BRE follows complex inheritance but it is possible that ADRESD may hold some valuable clues to the pathogenesis of BRE. PMID:11231219

  19. The psychosocial impact of epilepsy in childhood.

    PubMed

    Sillanpää, Matti; Helen Cross, J

    2009-06-01

    In addition to its medical impact with respect to loss of control, drug effects, and comorbidity, epilepsy has a marked impact on a child's life. Population-based studies show that 70-76% of children with epilepsy have some type of disability or handicap affecting their daily life and choices for the future. Comorbidity and, specifically, learning disability (sometimes referred to as mental retardation) modify the life of a child and the family. To improve these children's position in society, they should have the same opportunities and be allowed to make choices on the basis of their abilities, not their diagnosis of epilepsy. Supporting the development of acceptance, self-reliance, self-respect, and self-empowerment of children with epilepsy is crucial to their achieving a place in the community equal to their abilities. This is a challenging task for their families, relatives, schoolteachers, employers, and legislators. PMID:19298867

  20. Identifying and managing epilepsy in older adults.

    PubMed

    Austin, Jill; Abdulla, Aza

    Although epilepsy is often considered to be a condition that affects children and young people, the incidence of new-onset epilepsy has significantly increased among older people since the 1980s. In addition, it is set to rise further, placing an increasing burden on healthcare resources. One reason for this increase is the growth in the population of older people and in age-related conditions such as stroke and dementia, which predispose to epilepsy. The condition can easily go unrecognised in older people, and its symptoms can be dismissed as part of the ageing process or mistaken for other conditions, such as dementia, transient ischaemic attack or heart disease. This article discusses the presentation, diagnosis and treatment of epilepsy in older people. PMID:23431716

  1. Association Between Benzodiazepine Use and Epilepsy Occurrence

    PubMed Central

    Harnod, Tomor; Wang, Yu-Chiao; Kao, Chia-Hung

    2015-01-01

    Abstract We conducted a retrospective case–control study to evaluate the association between the risk of benzodiazepine (BZD) use and epilepsy occurrence by using data from the Taiwan National Health Insurance Research Database. We recruited 1065 participants who ages 20 years or older and newly diagnosed with epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification 345) between 2004 and 2011 and assigned them to the epilepsy group. We subsequently frequency-matched them with participants in a control group (n = 4260) according to sex, age, and index year at a 1:4 ratio. A logistic regression model was employed to calculate the odds ratio (OR) for association of epilepsy with BZD exposure. Multivariate logistic regression was conducted to estimate the dose–response relationship between BZD levels and epilepsy risk. The adjusted OR (aOR) for the association of epilepsy with BZD exposure was 2.02 (95% confidence interval [CI] = 1.68–2.42). The aOR for an average BZD dose increased to 1.26 for the participants on <0.01 defined daily dose (DDD), and increased to 4.32 for those on ≥1.50 DDD. On average, when the DDD of BZD exposure increased by 100 units, the epilepsy risk increase by 1.03-fold (95% CI = 1.01–1.04, P = 0.003). The annual BZD exposure day ranges were significantly associated with epilepsy (2–7 days: aOR = 1.67; 8–35 days: aOR = 3.16; and ≥35 days: aOR = 5.60). Whenever the annual BZD exposure increased by 30 days, the risk of epilepsy notably increased by 1.03-fold (95% CI = 1.01–1.04, P < 0.001). In addition, users who quit BZD for more than 6 months still exhibited a higher risk of epilepsy than did the non-BZD users. A considerable increase in epilepsy occurrence was observed in ones with BZD use, particularly in those with prolonged use, multiple exposure, and high-dose consumption. PMID:26376408

  2. Social cognition and epilepsy surgery.

    PubMed

    Kirsch, Heidi E

    2006-02-01

    Human social behavior depends on a set of perceptive, mnemonic, and interpretive abilities that together may be termed social cognition. Lesion and functional imaging studies of social cognitive functions implicate the temporal lobes (in particular, the nondominant temporal lobe) and mesial temporal structures as critical at the front end of social cognitive processes. The frontal lobes, in turn, function to interpret and to modulate these processes via top-down control. Damage to frontal regions is associated with specific derangements in social behavior. Chronic focal-onset epilepsy and its surgical treatment commonly affect these neuroanatomic regions and might therefore impact social function. Postoperative social function helps determine quality of life for both patients and families. There is some evidence that resective seizure surgery affects social cognition, but there are significant weaknesses in our current knowledge that can be overcome with comprehensive longitudinal research. PMID:16253567

  3. Drug treatment of epilepsy: a review

    PubMed Central

    Rosenbloom, David; Upton, Adrian R.M.

    1983-01-01

    Once a decision to treat epilepsy has been made it is necessary to have a thorough knowledge of the benefits, disadvantages, toxic effects, pharmacokinetics and interactions associated with each anticonvulsant. However, by determining the serum concentration and manipulating it within the therapeutic range it should be possible to find a regimen that adequately controls seizures without introducing unnecessary toxic effects. There are special considerations in choosing anticonvulsants to treat epilepsy in pregnancy, febrile convulsions and status epilepticus. PMID:6336967

  4. The modified atkins diet in refractory epilepsy.

    PubMed

    Sharma, Suvasini; Jain, Puneet

    2014-01-01

    The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Recent studies have shown good efficacy and tolerability of this diet in refractory epilepsy. In this review, we discuss the use of the modified Atkins diet in refractory epilepsy. PMID:24627806

  5. 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

  6. Anterior Cingulate epilepsy: mechanisms and modulation

    PubMed Central

    Chang, Wei-Pang; Shyu, Bai-Chuang

    2014-01-01

    Epilepsy is a common neurological disorder, about 1% population worldwide suffered from this disease. In 1989, the International League Against Epilepsy (ILAE) classified anterior cingulate epilepsy as a form of frontal lobe epilepsy (FLE). FLE is the second most common type of epilepsy. Previous clinical studies showed that FLE account an important cause in refractory epilepsy, therefore to find alternative approach to modulate FLE is very important. Basic research using animal models and brain slice have revealed some insights on the epileptogenesis and modulation of seizure in anterior cingulate cortex (ACC). Interneurons play an important role in the synchronization of cingulate epilepsy. Research has shown that the epileptogenesis of seizure originated from mesial frontal lobe might be caused by a selective increase in nicotine-evoked γ-aminobutyric acid (GABA) inhibition, because the application of the GABAA receptor antagonist picrotoxin inhibited epileptic discharges. Gap junctions are also involved in the regulation of cingulate epilepsy. Previous studies have shown that the application of gap junction blockers could attenuate ACC seizures, while gap junction opener could enhance them in an in vitro preparation. μ-Opioid receptors have been shown to be involved in the epileptic synchronization mechanism in ACC seizures in a brain slice preparation. Application of the μ-opioid agonist DAMGO significantly abolished the ictal discharges in a 4-aminopyridine induced electrographic seizure model in ACC. Basic research has also found that thalamic modulation has an inhibitory effect on ACC seizures. Studies have shown that the medial thalamus may be a target for deep brain stimulation to cure ACC seizures. PMID:24427123

  7. Management of epilepsy during pregnancy: an update.

    PubMed

    Patel, Sima I; Pennell, Page B

    2016-03-01

    The clinical management of women with epilepsy on antiepileptic drugs (AEDs) during pregnancy presents unique challenges. The goal of treatment is optimal seizure control with minimal in utero fetal exposure to AEDs in an effort to reduce the risk of structural and neurodevelopmental teratogenic effects. This paper reviews the following key issues pertaining to women with epilepsy during pregnancy: AED pharmacokinetics; clinical management of AEDs; seizure frequency; major congenital malformation; neurodevelopmental outcomes; perinatal complications; and breast feeding. PMID:27006699

  8. Knowledge about Epilepsy and Attitudes toward Students with Epilepsy among Middle and High School Teachers in Kuwait.

    PubMed

    Al-Hashemi, Eman; Ashkanani, Abdullatif; Al-Qattan, Haneen; Mahmoud, Asmaa; Al-Kabbani, Majd; Al-Juhaidli, Abdulaziz; Jaafar, Ahmad; Al-Hashemi, Zahraa

    2016-01-01

    Background and Objectives. Attitudes toward students with epilepsy and epilepsy-related knowledge of teachers are crucial for child's safety in the school. The aim of this study was to evaluate teachers' knowledge and attitudes toward epilepsy. Methods. This cross-sectional study included 824 teachers from 24 randomly selected middle and high schools. Scale of Attitudes Toward Persons with Epilepsy (ATPE) was modified to assess teachers' knowledge about epilepsy and attitudes toward students with epilepsy. Results. Median knowledge score about epilepsy was 5 (out of 13), while median attitude score was 10 (out of 15). Both knowledge and attitude median scores were significantly higher in senior teachers with longer teaching experience and in respondents who dealt with a person with epilepsy. There was significant association between knowledge score and attitude score (p < 0.01). Logistic regression showed that significant variables, independently associated with poor knowledge after adjusting for possible confounders, were not having a family member with epilepsy (p = 0.009), unawareness of life circumstances of persons with epilepsy (p = 0.048), and a poor attitude score (p < 0.001). Conclusion. School teachers in Kuwait have relatively poor knowledge about epilepsy but have positive attitudes toward students with epilepsy. A number of historical and stigmatizing ideas about epilepsy still exist. It is recommended to provide teachers with information about handling seizures in the educational setting through development and implementation of epilepsy education programs. PMID:27403170

  9. Knowledge about Epilepsy and Attitudes toward Students with Epilepsy among Middle and High School Teachers in Kuwait

    PubMed Central

    Al-Hashemi, Eman; Ashkanani, Abdullatif; Al-Kabbani, Majd; Al-Juhaidli, Abdulaziz; Jaafar, Ahmad

    2016-01-01

    Background and Objectives. Attitudes toward students with epilepsy and epilepsy-related knowledge of teachers are crucial for child's safety in the school. The aim of this study was to evaluate teachers' knowledge and attitudes toward epilepsy. Methods. This cross-sectional study included 824 teachers from 24 randomly selected middle and high schools. Scale of Attitudes Toward Persons with Epilepsy (ATPE) was modified to assess teachers' knowledge about epilepsy and attitudes toward students with epilepsy. Results. Median knowledge score about epilepsy was 5 (out of 13), while median attitude score was 10 (out of 15). Both knowledge and attitude median scores were significantly higher in senior teachers with longer teaching experience and in respondents who dealt with a person with epilepsy. There was significant association between knowledge score and attitude score (p < 0.01). Logistic regression showed that significant variables, independently associated with poor knowledge after adjusting for possible confounders, were not having a family member with epilepsy (p = 0.009), unawareness of life circumstances of persons with epilepsy (p = 0.048), and a poor attitude score (p < 0.001). Conclusion. School teachers in Kuwait have relatively poor knowledge about epilepsy but have positive attitudes toward students with epilepsy. A number of historical and stigmatizing ideas about epilepsy still exist. It is recommended to provide teachers with information about handling seizures in the educational setting through development and implementation of epilepsy education programs. PMID:27403170

  10. Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

    PubMed

    Shrot, Shai; Ramaty, Erez; Biala, Yoav; Bar-Klein, Guy; Daninos, Moshe; Kamintsky, Lyn; Makarovsky, Igor; Statlender, Liran; Rosman, Yossi; Krivoy, Amir; Lavon, Ophir; Kassirer, Michael; Friedman, Alon; Yaari, Yoel

    2014-09-01

    Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning. PMID:24881594

  11. Epilepsy

    MedlinePlus

    ... and it is not a sign of low intelligence. It is also not contagious. Seizures do not ... example, a partial seizure may cause changes in emotions, or to the senses (for example, hallucinations, numbness, ...

  12. History of epilepsy: nosological concepts and classification.

    PubMed

    Wolf, Peter

    2014-09-01

    The purpose of this review is to provide insight into the development of the nosological views of the epilepsies, from prehistoric times to the present, and highlight how these views are reflected by terminology an