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Sample records for absence epilepsy rats

  1. Neonatal sensory deprivation promotes development of absence seizures in adult rats with genetic predisposition to epilepsy.

    PubMed

    Sitnikova, Evgenia

    2011-03-04

    Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence seizures appear after puberty and they are increased with age. It is known that (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the critical period of development, could enhance excitatory activity in the somatosensory cortex. It is hypothesized that the cortex may become more excitable after neonatal vibrissae removal, and this may precipitate absence seizures in adult rats. We found that whisker trimming during the first postnatal weeks caused more rapid development of EEG seizure activity in adult WAG/Rij rats. Epileptic discharges in the trimmed rats were more numerous (vs control), showed longer duration and often appeared in desynchronized and drowsy EEG. The number of absence-like spindle-shaped EEG events (spike-wave spindles) in the whisker-trimmed rats was higher than in control, especially during the intermediate sleep state. An age-dependent increase of intermediate sleep state was found in the trimmed rats, but not in the intact animals. We discuss epigenetic factors that can modulate absence epilepsy in genetically prone subjects.

  2. The Genetic Absence Epilepsy Rats from Strasbourg model of absence epilepsy exhibits alterations in fear conditioning and latent inhibition consistent with psychiatric comorbidities in humans.

    PubMed

    Marks, Wendie N; Cavanagh, Mary E; Greba, Quentin; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2016-01-01

    Behavioural, neurological, and genetic similarities exist in epilepsies, their psychiatric comorbidities, and various psychiatric illnesses, suggesting common aetiological factors. Rodent models of epilepsy are used to characterize the comorbid symptoms apparent in epilepsy and their neurobiological mechanisms. The present study was designed to assess Pavlovian fear conditioning and latent inhibition in a polygenetic rat model of absence epilepsy, i.e. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the non-epileptic control (NEC) strain. Electrophysiological recordings confirmed the presence of spike-wave discharges in young adult GAERS but not NEC rats. A series of behavioural tests designed to assess anxiety-like behaviour (elevated plus maze, open field, acoustic startle response) and cognition (Pavlovian conditioning and latent inhibition) was subsequently conducted on male and female offspring. Results showed that GAERS exhibited significantly higher anxiety-like behaviour, a characteristic reported previously. In addition, using two protocols that differed in shock intensity, we found that both sexes of GAERS displayed exaggerated cued and contextual Pavlovian fear conditioning and impaired fear extinction. Fear reinstatement to the conditioned stimuli following unsignalled footshocks did not differ between the strains. Male GAERS also showed impaired latent inhibition in a paradigm using Pavlovian fear conditioning, suggesting that they may have altered attention, particularly related to previously irrelevant stimuli in the environment. Neither the female GAERS nor NEC rats showed evidence of latent inhibition in our paradigm. Together, the results suggest that GAERS may be a particularly useful model for assessing therapeutics designed to improve the emotional and cognitive disturbances associated with absence epilepsy.

  3. 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…

  4. Extracellular GABA in the ventrolateral thalamus of rats exhibiting spontaneous absence epilepsy: a microdialysis study.

    PubMed

    Richards, D A; Lemos, T; Whitton, P S; Bowery, N G

    1995-10-01

    There is compelling evidence that excessive GABA-mediated inhibition may underlie the abnormal electrical activity, initiated in the thalamus, associated with epileptic absence seizures. In particular, the GABAB receptor subtype seems to play a critical role, because its antagonists are potent inhibitors of absence seizures, whereas its agonists exacerbate seizure activity. Using a validated rat model of absence epilepsy, we have previously found no evidence of abnormal GABAB receptor density or affinity in thalamic tissue. In the present study, we have used in vivo microdialysis to monitor changes in levels of extracellular GABA and other amino acids in this brain region. We have shown that basal extracellular levels of GABA and, to a lesser extent, taurine are increased when compared with values in nonepileptic controls. However, modifying GABAergic transmission with the GABAB agonist (-)-baclofen (2 mg/kg i.p.), the GABAB antagonist CGP-35348 (200 mg/kg i.p.), or the GABA uptake inhibitor tiagabine (100 microM) did not produce any further alteration in extracellular GABA levels, despite the ability of these compounds to increase (baclofen and tiagabine) or decrease (CGP-35348) seizure activity. These findings suggest that the increased basal GABA levels observed in this animal model are not simply a consequence of seizure activity but may contribute to the initiation of absence seizures.

  5. 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.

  6. The ketogenic diet has no effect on the expression of spike-and-wave discharges and nutrient transporters in genetic absence epilepsy rats from Strasbourg.

    PubMed

    Nehlig, Astrid; Dufour, Franck; Klinger, Marianne; Willing, Lisa B; Simpson, Ian A; Vannucci, Susan J

    2009-05-01

    The genetic absence epilepsy rat from Strasbourg is considered an isomorphic, predictive, and homologous model of typical childhood absence epilepsy. It is characterized by the expression of spike-and-wave discharges (SWDs) in the thalamus and cortex. The ketogenic diet (KD) is successfully used in humans and animals with various types of seizures, but was not effective in children with intractable atypical absence epilepsy. Here, we studied its potential impact on the occurrence of SWDs in genetic absence epilepsy rat from Strasbourg. Rats were fed the KD for 3 weeks during which they were regularly subjected to the electroencephalographic recording of SWDs. The KD did not influence the number and duration of SWDs despite a 15-22% decrease in plasma glucose levels and a large increase in beta-hydroxybutyrate levels. Likewise, the KD did not affect the level of expression of the blood-brain barrier glucose transporter GLUT1 or of the monocarboxylate transporters, MCT1 and MCT2. This report extends the observation in humans that the KD does not appear to show effectiveness in intractable atypical absence epilepsy to this model of typical childhood absence epilepsy which responds to specific antiepileptic drugs.

  7. Evaluation of GAD67 immunoreactivity in the region of substantia nigra pars reticulata in resistance to development of convulsive seizure in genetic absence epilepsy rats

    PubMed Central

    Gulcebi, Medine; Akman, Ozlem; Carcak, Nihan; Karamahmutoglu, Tugba; Onat, Filiz

    2016-01-01

    OBJECTIVE: Nonconvulsive absence epilepsy and convulsive epilepsy seizures are rarely seen in the same patient. It has been demonstrated that there is a resistance to development of convulsive seizures in genetic absence epilepsy models. The present study investigated glutamic acid decarboxylase (GAD) immunoreactivity in the brain region related to the interaction of these two seizure types, namely substantia nigra pars reticulata (SNR) subregions, SNRanterior and SNRposterior. METHODS: Nonepileptic adult male Wistar rats and Genetic Absence Epilepsy Rats from Strasbourg (GAERS) were used. Experimental groups of Wistar and GAERS were electrically stimulated for kindling model to induce convulsive epileptic seizures. An electrical stimulation cannula was stereotaxically implanted to the basolateral amygdala and recording electrodes were placed on the cortex. Sagittal sections of SNR were used to evaluate immunohistochemical reaction. Sections were incubated with anti-GAD67 antibody. Densitometric analysis of GAD67 immunoreactive neurons was performed using photographs of stained sections. One-way analysis of variance and post hoc Bonferroni test were used for statistical analysis of the data. RESULTS: There was no difference in GAD67 immunoreactivity of SNR subregions of control Wistar and control GAERS. An increase in GAD67 immunoreactivity was detected in SNRposterior subregion of stimulated Wistar rats, whereas there was a decrease in GAD67 immunoreactivity in SNRposterior of stimulated GAERS. The difference in GAD67 immunoreactivity between these two groups was statistically significant. CONCLUSION: Level of synthetized gamma-aminobutyric acid in SNRposterior subregion plays an important role in the interaction of nonconvulsive absence epilepsy seizures and convulsive epilepsy seizures. PMID:28275746

  8. 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.

  9. 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.

  10. Comparison of cortical epileptic afterdischarges in immature genetic absence epilepsy WAG/Rij rats with those in two other strains (ACI and Wistar).

    PubMed

    Mares, Pavel; Tolmacheva, Elena

    2007-01-01

    The aim of this study was to examine the development of cortical epileptic afterdischarges (ADs) in genetic absence epilepsy WAG/Rij rats, and to compare them with two strains with minimal incidence of spike-and-wave (SW) episodes (ACI and Wistar). Epileptic ADs were elicited by stimulation of sensorimotor cortex in 12-, 18-, and 25-day-old rats of the three strains. The threshold current intensities were established for movements accompanying stimulation, for ADs of the SW type and accompanying clonic seizures and for transition into limbic type of ADs (characterized by behavioral automatisms). Individual groups were formed by 7-12 rats. There were no differences among the three strains in the thresholds for elicitation of stimulation-bound movements. In contrast, WAG/Rij and ACI rats exhibited easier elicitation of SW ADs than Wistar rats at the age of 18 and 25 days. There was no difference among the three strains in transition into the limbic type of ADs in 18- and 25-day-old rats. Lower thresholds for SW ADs in 18- and 25-day-old WAG/Rij and ACI rats in comparison with Wistar rats are in agreement with our data from adult animals as well as with development of pharmacologically induced models of absence seizures. The failure to find a specific difference between WAG/Rij rats and the other two strains might indicate a difference in generation of SW episodes and SW cortical AD.

  11. 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

  12. Effect of caffeine and adenosine receptor ligands on the expression of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS).

    PubMed

    Germé, Katuschia; Faure, Jean-Baptiste; Koning, Estelle; Nehlig, Astrid

    2015-02-01

    The influence of caffeine on epileptic seizures remains a matter of debate. Here we tested on Genetic Absence Epilepsy Rats from Strasbourg (GAERS) the consequences of acute and chronic exposure to caffeine on the expression of spike-and-wave discharges (SWDs). Since caffeine is a mixed nonspecific A(1) and A(2A) adenosine receptor antagonist, we measured also the influence of antagonists and agonists of these receptors on SWD expression. GAERS were equipped with four cortical electrodes over the frontoparietal cortex and the cumulated duration and number of SWDs were recorded for 120 min after the injection of increasing doses of caffeine, specific antagonists and agonists of A(1) and A(2A) adenosine receptors. The effects of chronic caffeine were also studied. In GAERS, caffeine dose-dependently reduced the cumulated number and duration of SWDs which almost disappeared after the injection of the two highest doses of caffeine, 5 and 10 mg/kg. Likewise, the A(1) and A(2A) adenosine receptor antagonists led to a dose-dependent reduction of SWD expression while the agonists dose-dependently increased SWD expression. Conversely, the chronic exposure to caffeine via drinking water for 15 days did not influence SWD expression. With the exception of the two highest doses of caffeine that largely enhanced activity, all compounds including low doses of caffeine had no effect on locomotor activity of GAERS. These data show that the acute exposure to low doses of caffeine, or A(1) and A(2A) adenosine receptor antagonists reduces SWD expression in GAERS, independently from any effect on motor activity. The chronic exposure of GAERS to caffeine does not affect the expression of epilepsy.

  13. 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

  14. The double generalization phenomenon in juvenile absence epilepsy.

    PubMed

    San-Juan, Daniel; Mayorga, Adriana Patricia M; Anschel, David J; Avellán, Alvaro Moreno; González-Aragón, Maricarmen F; Cole, Andrew J

    2011-07-01

    The characterization of a seizure as generalized or focal onset depends on a basic knowledge of the underlying pathophysiology. Recently, an uncommon phenomenon in generalized epilepsy-evolution of seizures from generalized to focal followed by secondary generalization-was reported for the first time. We describe a 15-year-old boy, initially classified as having partial epilepsy, who had a typical absence seizure that became focal with second secondary generalization (double generalization). On the basis of these findings his epilepsy was classified as juvenile absence epilepsy and his treatment was changed, resulting in seizure freedom. This is the first report of this unusual electroclinical evolution in a patient with juvenile absence epilepsy. The recognition of this particular pattern allows correct classification and impacts both treatment and prognosis.

  15. Pretreatment EEG in childhood absence epilepsy

    PubMed Central

    Shinnar, Shlomo; Cnaan, Avital; Hu, Fengming; Moshé, Solomon; Mizrahi, Eli; Masur, David; Sogawa, Yoshi; Le Pichon, J.B.; Levine, Calley; Hirtz, Deborah; Clark, Peggy; Adamson, Peter C.; Glauser, Tracy

    2013-01-01

    Objective: In children with newly diagnosed childhood absence epilepsy (CAE), determine pretreatment EEG features and their associations with baseline neuropsychological function and short-term treatment outcome. Methods: In a multicenter, randomized clinical trial, patients with CAE underwent a pretreatment, 1-hour video-EEG and neuropsychological testing with freedom-from-failure and seizure-freedom (SF) outcome assessed at the 16- to 20-week visit. Results: Detailed evaluation of the pretreatment EEG was possible for 99.8% of participants (445/446). Median time to first seizure was 6.0 minutes (range 0–59 minutes), median number of seizures was 5 (range 1–60), and median seizure duration was 10.8 seconds (range 3.3–77.6 seconds). Median duration of shortest seizure per EEG was 7.5 seconds (range 3.0–77.6 seconds). Seizure frequency was not associated with baseline measures of attention, executive function, or treatment outcome. Presence of a seizure lasting ≥20 seconds was noted in 29% of subjects (129/440); these children had higher median omissions T score on the Conners Continuous Performance Test (56.3 vs 51.6, p = 0.01). Patients with a shortest seizure of longer duration were more likely to demonstrate treatment success by both freedom-from-failure (p = 0.02) and SF (p = 0.005) criteria, even after controlling for age, treatment group, and number of seizures, with good predictive value (area under the curve 78% for SF). Conclusions: CAE is reliably and quickly confirmed by EEG. Occurrence of a seizure ≥20 seconds, but not overall seizure frequency, was associated with differential baseline measures of attention. Patients whose shortest pretreatment EEG seizure was longer in duration were more likely to achieve SF, regardless of treatment. PMID:23719147

  16. 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.

  17. 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

  18. 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

  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. 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

  1. 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

  2. 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

  3. Differentiation of attention-related problems in childhood absence epilepsy.

    PubMed

    Vega, Clemente; Vestal, Matthew; DeSalvo, Matthew; Berman, Rachel; Chung, Mihae; Blumenfeld, Hal; Spann, Marisa N

    2010-09-01

    The current study examined the specific types of attention-related problems children with childhood absence epilepsy (CAE) experience and the role of disease factors in the development of attention-related problems. Thirty-eight subjects with CAE and 46 healthy controls, aged 6 to 16, participated in the study. The Behavior Assessment System for Children (BASC) was completed by parents, and the Attention Problems and Hyperactivity subscales were used to characterize the problems of children with CAE. Item analysis within the subscales revealed that children with CAE demonstrate higher rates of hyperactive (overactivity and fidgetiness) and inattentive (forgetfulness and distractibility) problems, and require more supervision. Within-CAE-group analyses revealed that those who were actively having seizures were more impatient and those with a longer duration of illness were less proficient in completing homework. Children with CAE are at risk for certain inattentive and hyperactive problems, which can differ depending on duration of illness and active seizure status.

  4. 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

  5. Feasibility of a Mobile Cognitive Intervention in Childhood Absence Epilepsy

    PubMed Central

    Glynn, Peter; Eom, Soyong; Zelko, Frank; Koh, Sookyong

    2016-01-01

    Children with childhood absence epilepsy (CAE) frequently present with cognitive comorbidities and school performance concerns. The present study evaluated the feasibility of an intervention for such comorbidities using a mobile cognitive therapy application on an iPad. Eight children with CAE and school concerns aged 7–11 participated in a 4-week intervention. They were asked to use the application for 80 min per week (20 min/day, 4 times/week). Parents and children completed satisfaction surveys regarding the application. Participants were evaluated before and after the intervention using the Cognitive Domain of the NIH Toolbox and by parental completion of the Behavioral Rating Inventory of Executive Function. All eight patients completed the study, using the iPad for an average of 78 min/week. Children and parents reported high satisfaction with the application. Though a demonstration of efficacy was not the focus of the study, performance improvements were noted on a processing speed task and on a measure of fluid intelligence. An iPad based cognitive therapy was found to be a feasible intervention for children with CAE. PMID:27895568

  6. Wireless system for long-term EEG monitoring of absence epilepsy

    NASA Astrophysics Data System (ADS)

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

    2002-11-01

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

  7. Assessment of the Attention Impairment in Absence Epilepsy: Comparison of Visual and Auditory P300

    PubMed Central

    Duncan, Connie C.; Mirsky, Allan F.; Lovelace, Christopher T.; Theodore, William H.

    2009-01-01

    We report an investigation of P300 measures of information processing in patients with generalized epilepsy of the absence type and those with complex partial epilepsy. Studies have demonstrated that absence patients perform more poorly than complex partial patients on behavioral tests of sustained attention (the Continuous Performance Test, or CPT). Duncan (1988) reported that P300 was significantly reduced in a group of absence patients as compared with healthy controls. The present investigation was undertaken to compare the attention deficit in absence patients to that in complex partial seizure patients. Thus, ERPs were recorded while participants with absence seizure disorder, complex partial seizure disorder, and healthy controls performed auditory and visual versions of the CPT. A significant reduction in the amplitude of P300 on the visual CPT was observed in both groups of seizure patients as compared to controls. In contrast, P300 on the auditory CPT was reduced only in the group with absence seizures. These ERP data support and amplify previous behavioral findings of the impaired capacity of absence patients to mobilize and sustain attentional resources. Auditory sustained attention seems to be more affected by the pathophysiology of absence epilepsy than visual attention. Two possible factors may be involved: (a) There are separate visual and auditory attention systems in the brain, and the latter is more vulnerable than the former (Duncan et al., 2005); and (b) Auditory processing depends on intact mechanisms in the brainstem, which are dysfunctional in patients with absence seizures. PMID:19414047

  8. 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

  9. Endogenous rhythm of absence epilepsy: relationship with general motor activity and sleep-wake states.

    PubMed

    Smyk, Magdalena K; Coenen, Anton M L; Lewandowski, Marian H; van Luijtelaar, Gilles

    2011-02-01

    The rhythms of spontaneously occurring seizures (spike-wave discharges, SWD) and motor activity, as well as the relationship between SWD and sleep-wake states were investigated in the WAG/Rij rat model of absence epilepsy. In order to establish whether SWD are controlled by external (Zeitgebers) or by endogenous factors such as circadian influences or the state of vigilance, the study was performed in entrained and constant dim light conditions. EEG and motor activity were recorded in the 12:12 light-dark cycle and in constant dim light conditions. Circadian rhythmicity was found both for motor activity and the occurrence of SWD in conditions of entrainment. In constant dim light conditions also circadian rhythms emerged, however, the change in circadian parameters was opposite for the rhythm of SWD and motor activity. SWD were preceded mostly by passive wakefulness and by slow-wave sleep in both experimental conditions. It can be concluded that the rhythm of SWD seems to be generated and controlled by an endogenous mechanism distinct from that which controls the rhythm of motor activity. The relationship between SWD and sleep-wake states preceding their occurrences appeared to be unchanged, suggesting that the mechanism of generation of SWD is independent of the circadian timing system.

  10. 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.

  11. 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

  12. 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.

  13. Electric stimulation of the tuberomamillary nucleus affects epileptic activity and sleep-wake cycle in a genetic absence epilepsy model.

    PubMed

    Blik, Vitaliya

    2015-01-01

    Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy.

  14. Structural Abnormalities in Childhood Absence Epilepsy: Voxel-Based Analysis Using Diffusion Tensor Imaging

    PubMed Central

    Qiu, Wenchao; Gao, Yuan; Yu, Chuanyong; Miao, Ailiang; Tang, Lu; Huang, Shuyang; Hu, Zheng; Xiang, Jing; Wang, Xiaoshan

    2016-01-01

    Purpose: Childhood absence epilepsy (CAE) is a common syndrome of idiopathic generalized epilepsy. However, little is known about the brain structural changes in this type of epilepsy, especially in the default mode network (DMN) regions. This study aims at using the diffusion tensor imaging (DTI) technique to quantify structural abnormalities of DMN nodes in CAE patients. Method: DTI data were acquired in 14 CAE patients (aged 8.64 ± 2.59 years, seven females and seven males) and 16 age- and sex-matched healthy controls. The data were analyzed using voxel-based analysis (VBA) and statistically compared between patients and controls. Pearson correlation was explored between altered DTI metrics and clinical parameters. The difference of brain volumes between patients and controls were also tested using unpaired t-test. Results: Patients showed significant increase of mean diffusivity (MD) and radial diffusivity (RD) in left medial prefrontal cortex (MPFC), and decrease of fractional anisotropy (FA) in left precuneus and axial diffusivity (AD) in both left MPFC and precuneus. In correlation analysis, MD value from left MPFC was positively associated with duration of epilepsy. Neither the disease duration nor the seizure frequency showed significant correlation with FA values. Between-group comparison of brain volumes got no significant difference. Conclusion: The findings indicate that structural impairments exist in DMN regions in children suffering from absence epilepsy and MD values positively correlate with epilepsy duration. This may contribute to understanding the pathological mechanisms of chronic neurological deficits and promote the development of new therapies for this disorder. PMID:27733824

  15. 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

  16. Epilepsy

    MedlinePlus

    ... de los dientes Video: Getting an X-ray 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 ...

  17. Epilepsy

    MedlinePlus

    ... Emergency Room? What Happens in the Operating Room? Epilepsy KidsHealth > For Kids > Epilepsy A A A What's ... With Epilepsy Different? en español Epilepsia What Is Epilepsy? Epilepsy comes from a Greek word meaning "to ...

  18. [Functional state of cardiovascular system by progressive absences--epilepsy and its treatment].

    PubMed

    Mamalyga, M L

    2014-05-01

    Age-dependent increase of seizure activity at absence epilepsy exacerbates hemodynamic and autonomic regulation of heart rate. Cardiac dysfunction is accompanied by an increasing duration of intervals repolarization left ventricular QTc, which causes the risk of life-threatening arrhythmias, increases the threat of sudden cardiac death. Anticonvulsant drug therapy provides an opportunity to improve the functional state of the cardiovascular system, if not exceeded a certain level of seizure activity of the brain. This possibility remains as long as the progressive seizure activity isn't reaches a certain level. Later anticonvulsant drug therapy reduces seizure activity of the brain, but does not improve the functional state of heart.

  19. Epilepsy

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Epilepsy KidsHealth > For Teens > Epilepsy A A A What's ... embarrass himself or scare his friends. What Is Epilepsy? Epilepsy is a condition of the nervous system ...

  20. Multimodal neuroimaging investigations of alterations to consciousness: the relationship between absence epilepsy and sleep.

    PubMed

    Bagshaw, Andrew P; Rollings, David T; Khalsa, Sakh; Cavanna, Andrea E

    2014-01-01

    The link between epilepsy and sleep is well established on many levels. The focus of the current review is on recent neuroimaging investigations into the alterations of consciousness that are observed during absence seizures and the descent into sleep. Functional neuroimaging provides simultaneous cortical and subcortical recording of activity throughout the brain, allowing a detailed definition and characterization of large-scale brain networks and the interactions between them. This has led to the identification of a set of regions which collectively form the consciousness system, which includes contributions from the default mode network (DMN), ascending arousal systems, and the thalamus. Electrophysiological and neuroimaging investigations have also clearly demonstrated the importance of thalamocortical and corticothalamic networks in the evolution of sleep and absence epilepsy, two phenomena in which the subject experiences an alteration to the conscious state and a disconnection from external input. However, the precise relationship between the consciousness system, thalamocortical networks, and consciousness itself remains to be clarified. One of the fundamental challenges is to understand how distributed brain networks coordinate their activity in order to maintain and implement complex behaviors such as consciousness and how modifications to this network activity lead to alterations in consciousness. By taking into account not only the level of activation of individual brain regions but also their connectivity within specific networks and the activity and connectivity of other relevant networks, a more specific quantification of brain states can be achieved. This, in turn, may provide a more fundamental understanding of the alterations to consciousness experienced in sleep and epilepsy.

  1. Electroclinical features of idiopathic generalised epilepsy with persisting absences in adult life.

    PubMed Central

    Michelucci, R; Rubboli, G; Passarelli, D; Riguzzi, P; Volpi, L; Parmeggiani, L; Rizzi, R; Gardella, E; Tassinari, C A

    1996-01-01

    OBJECTIVES: To describe the electroclinical features of typical absences persisting in adult life. METHODS: Twelve adult patients (aged 21 to 56 years) with idiopathic generalised epilepsy featuring typical absences as the prominent clinical feature were studied. All patients underwent a full clinical and neurophysiological investigation including ictal documentation of seizures. RESULTS: Neurological examination and neuroradiological investigations were normal in all cases. Clinical findings included a median age at onset of absences of 14 (range 4-32) years, almost constant tonic-clonic seizures (in 83% of patients), frequent episodes of absence status (in 33% of patients), and associated cognitive or psychiatric disturbances. Interictal EEG findings showed normal background activity, generalised paroxysms of spike waves or polyspike waves, and inconstant focal spikes (in five patients); runs of polyspikes were seen during non-REM sleep. Ictal EEG findings showed generalised spike waves at 3 Hz, sometimes preceded by multiple spikes, or more complex EEG patterns with sequences of polyspikes intermingled with spike waves or polyspike waves, showing discharge fragmentation or variation of intradischarge frequency. CONCLUSION: The results of the present study show that absences persisting in adult life may show particular clinical and EEG patterns, distinct from those in childhood or adolescence. PMID:8937341

  2. Does Pilocarpine-Induced Epilepsy in Adult Rats Require Status epilepticus?

    PubMed Central

    Navarro Mora, Graciela; Bramanti, Placido; Osculati, Francesco; Chakir, Asmaa; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea; Fabene, Paolo Francesco

    2009-01-01

    Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE) is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a) whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS) and b) whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22) months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy. PMID:19503612

  3. 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.

  4. Behavioral impairments in rats with chronic epilepsy suggest comorbidity between epilepsy and attention deficit/hyperactivity disorder.

    PubMed

    Pineda, Eduardo; Jentsch, J David; Shin, Don; Griesbach, Grace; Sankar, Raman; Mazarati, Andrey

    2014-02-01

    Attention deficit/hyperactivity disorder (ADHD) is encountered among patients with epilepsy at a significantly higher rate than in the general population. Mechanisms of epilepsy-ADHD comorbidity remain largely unknown. We investigated whether a model of chronic epilepsy in rats produces signs of ADHD, and thus, whether it can be used for studying mechanisms of this comorbidity. Epilepsy was induced in male Wistar rats via pilocarpine status epilepticus. Half of the animals exhibited chronic ADHD-like abnormalities, particularly increased impulsivity and diminished attention in the lateralized reaction-time task. These impairments correlated with the suppressed noradrenergic transmission in locus coeruleus outputs. The other half of animals exhibited depressive behavior in the forced swimming test congruently with the diminished serotonergic transmission in raphe nucleus outputs. Attention deficit/hyperactivity disorder and depressive behavior appeared mutually exclusive. Therefore, the pilocarpine model of epilepsy affords a system for reproducing and studying mechanisms of comorbidity between epilepsy and both ADHD and/or depression.

  5. Ethosuximide, Valproic Acid and Lamotrigine in Childhood Absence Epilepsy: Initial Monotherapy Outcomes at 12 months

    PubMed Central

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

    2012-01-01

    Purpose Determine the optimal initial monotherapy for children with newly diagnosed childhood absence epilepsy based on 12 months of double blind therapy. Methods A double-blind, randomized controlled clinical trial compared the efficacy, tolerability and neuropsychological effects of ethosuximide, valproic acid and lamotrigine in children with newly diagnosed childhood absence epilepsy. Study medications were titrated to clinical response and subjects remained in the trial unless they reached a treatment failure criterion. Maximal target doses were ethosuximide 60 mg/kg/day or 2000 mg/day, valproic acid 60 mg/kg/day or 3000 mg/day and lamotrigine 12 mg/kg/day or 600 mg/day. Original primary outcome was at 16–20 weeks and included a video EEG assessment. For this report, the main effectiveness outcome was the freedom from failure rate 12 months after randomization and included a video EEG assessment; differential drug effects were determined by pairwise comparisons. The main cognitive outcome was the percentage of subjects experiencing attentional dysfunction at the Month 12 visit. Key Findings A total of 453 children were enrolled and randomized; seven were deemed ineligible and 446 subjects comprised the overall efficacy cohort. There were no demographic differences between the three cohorts. By 12 months after starting therapy, only 37% of all enrolled subjects were free from treatment failure on their first medication. At the Month 12 visit, the freedom-from-failure rates for ethosuximide and valproic acid were similar (45% and 44%, respectively; odds ratio with valproic acid vs. ethosuximide, 0.94; 95% confidence interval [CI], 0.60 to 1.48; P = 0.82) and were higher than the rate for lamotrigine (21%; odds ratio with ethosuximide vs. lamotrigine, 3.09; 95% CI, 1.86 to 5.13; odds ratio with valproic acid vs. lamotrigine, 2.90; 95% CI, 1.74 to 4.83; P<0.001 for both comparisons). The frequency of treatment failures due to lack of seizure control (p < 0

  6. NMDA Receptor Expression in the Thalamus of the Stargazer Model of Absence Epilepsy

    PubMed Central

    Barad, Z.; Grattan, D. R.; Leitch, B.

    2017-01-01

    In the stargazer mouse model of absence epilepsy, altered corticothalamic excitation of reticular thalamic nucleus (RTN) neurons has been suggested to contribute to abnormal synchronicity in the corticothalamic-thalamocortical circuit, leading to spike-wave discharges, the hallmark of absence seizures. AMPA receptor expression and function are decreased in stargazer RTN, due to a mutation of AMPAR auxiliary subunit stargazin. It is unresolved and debated, however, if decreased excitation of RTN is compatible with epileptogenesis. We tested the hypothesis that relative NMDAR expression may be increased in RTN and/or thalamic synapses in stargazers using Western blot on dissected thalamic nuclei and biochemically isolated synapses, as well as immunogold cytochemistry in RTN. Expression of main NMDAR subunits was variable in stargazer RTN and relay thalamus; however, mean expression values were not statistically significantly different compared to controls. Furthermore, no systematic changes in synaptic NMDAR levels could be detected in stargazer thalamus. In contrast, AMPAR subunits were markedly decreased in both nucleus-specific and synaptic preparations. Thus, defective AMPAR trafficking in stargazer thalamus does not appear to lead to a ubiquitous compensatory increase in total and synaptic NMDAR expression, suggesting that elevated NMDAR function is not mediated by changes in protein expression in stargazer mice. PMID:28220891

  7. 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. ...

  8. 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, ...

  9. Altered Effective Connectivity Network in Childhood Absence Epilepsy: A Multi-frequency MEG Study.

    PubMed

    Wu, Caiyun; Xiang, Jing; Jiang, Wenwen; Huang, Shuyang; Gao, Yuan; Tang, Lu; Zhou, Yuchen; Wu, Di; Chen, Qiqi; Hu, Zheng; Wang, Xiaoshan

    2017-03-12

    Using multi-frequency magnetoencephalography (MEG) data, we investigated whether the effective connectivity (EC) network of patients with childhood absence epilepsy (CAE) is altered during the inter-ictal period in comparison with healthy controls. MEG data from 13 untreated CAE patients and 10 healthy controls were recorded. Correlation analysis and Granger causality analysis were used to construct an EC network at the source level in eight frequency bands. Alterations in the spatial pattern and topology of the network in CAE were investigated by comparing the patients with the controls. The network pattern was altered mainly in 1-4 Hz, showing strong connections within the frontal cortex and weak connections in the anterior-posterior pathways. The EC involving the precuneus/posterior cingulate cortex (PC/PCC) significantly decreased in low-frequency bands. In addition, the parameters of graph theory were significantly altered in several low- and high-frequency bands. CAE patients display frequency-specific abnormalities in the network pattern even during the inter-ictal period, and the frontal cortex and PC/PCC might play crucial roles in the pathophysiology of CAE. The EC network of CAE patients was over-connective and random during the inter-ictal period. This study is the first to reveal the frequency-specific alteration in the EC network during the inter-ictal period in CAE patients. Multiple-frequency MEG data are useful in investigating the pathophysiology of CAE, which can serve as new biomarkers of this disorder.

  10. Seizures and reproductive function: insights from female rats with epilepsy

    PubMed Central

    Scharfman, Helen E.; Kim, Michelle; Hintz, Tana M.; MacLusky, Neil J.

    2009-01-01

    OBJECTIVE Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome (PCOS), but it has been difficult to dissociate the effects of epilepsy per se from the role of antiepileptic drugs (AEDs). To distinguish the effects of chronic seizures from AEDs, we used the laboratory rat, where an epileptic condition can be induced without concomitant AED treatment. METHODS Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus (SE), which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed “epileptic.” Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop SE. Ovarian cyclicity and weight gain were evaluated for 2-3 months. Serum hormone levels were assayed from trunk blood, collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if SE did not occur. Ovarian cysts and weight gain were significantly greater in epileptic rats than controls, whether rats maintained cyclicity or not. Serum testosterone was elevated in epileptic rats, but estradiol, progesterone and prolactin were not. INTERPRETATIONS The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels. Although caution is required when comparing female rats to women, the data suggest that epilepsy per se may be sufficient to induce abnormalities in the control of the ovary. PMID:19107990

  11. 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.

  12. Long-term outcomes of generalized tonic-clonic seizures in a childhood absence epilepsy trial

    PubMed Central

    Cnaan, Avital; Hu, Fengming; Clark, Peggy; Dlugos, Dennis; Hirtz, Deborah G.; Masur, David; Mizrahi, Eli M.; Moshé, Solomon L.; Glauser, Tracy A.

    2015-01-01

    Objective: To determine incidence and early predictors of generalized tonic-clonic seizures (GTCs) in children with childhood absence epilepsy (CAE). Methods: Occurrence of GTCs was determined in 446 children with CAE who participated in a randomized clinical trial comparing ethosuximide, lamotrigine, and valproate as initial therapy for CAE. Results: As of June 2014, the cohort had been followed for a median of 7.0 years since enrollment and 12% (53) have experienced at least one GTC. The median time to develop GTCs from initial therapy was 4.7 years. The median age at first GTC was 13.1 years. Fifteen (28%) were not on medications at the time of their first GTC. On univariate analysis, older age at enrollment was associated with a higher risk of GTCs (p = −0.0009), as was the duration of the shortest burst on the baseline EEG (p = 0.037). Failure to respond to initial treatment (p < 0.001) but not treatment assignment was associated with a higher rate of GTCs. Among patients initially assigned to ethosuximide, 94% (15/16) with GTCs experienced initial therapy failure (p < 0.0001). A similar but more modest effect was noted in those initially treated with valproate (p = 0.017) and not seen in those initially treated with lamotrigine. Conclusions: The occurrence of GTCs in a well-characterized cohort of children with CAE appears lower than previously reported. GTCs tend to occur late in the course of the disorder. Children initially treated with ethosuximide who are responders have a particularly low risk of developing subsequent GTCs. PMID:26311751

  13. 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

  14. A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA).

    PubMed

    Klitten, Laura L; Møller, Rikke S; Nikanorova, Marina; Silahtaroglu, Asli; Hjalgrim, Helle; Tommerup, Niels

    2011-12-01

    Epilepsy with myoclonic absences (EMA) is a rare form of generalized epilepsy occurring in childhood and is often difficult to treat. The underlying etiology of EMA is unknown in the majority of patients. Herein, we describe a patient with EMA and intellectual disability who carries a de novo balanced translocation: t(6;22)(p21.32;q11.21). We mapped the translocation breakpoints by fluorescence in situ hybridization (FISH), and the breakpoint at 6p21.32 was found to truncate the N-methyl-d-aspartate (NMDA)-receptor associated gene SYNGAP1. The breakpoint at 22q11.21 was within a highly variable region without known protein-coding genes. Mutations of SYNGAP1 are associated with nonsyndromal intellectual disability (NSID). Two-thirds of the patients described so far also have generalized epilepsy. This finding, together with our report, suggests that dysfunction of SYNGAP1 contributes to the development of generalized epilepsy, including EMA.

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

    PubMed

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

    2016-09-03

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

  16. Epilepsy

    MedlinePlus

    ... of basic, translational, and clinical research on the processes by which epilepsy develops, including mechanisms associated with brain malformations, genetic defects, and precipitating insults like TBI, stroke, brain tumor, childhood febrile seizures, or infection. These studies are identifying ...

  17. Epilepsy

    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 ...

  18. Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome.

    PubMed

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

    2013-07-19

    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.

  19. 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

  20. Absence of gender effect on amygdala volume in temporal lobe epilepsy.

    PubMed

    Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

    2010-11-01

    Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres.

  1. 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

  2. Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: a MEG study.

    PubMed

    Sakurai, Kotaro; Takeda, Youji; Tanaka, Naoaki; Kurita, Tsugiko; Shiraishi, Hideaki; Takeuchi, Fumiya; Nakane, Shingo; Sueda, Keitaro; Koyama, Tsukasa

    2010-05-01

    This study uses magnetoencephalography (MEG) to examine whether cortical regions that constitute a default mode network are involved during generalized spike-wave discharges (GSWs) in patients with juvenile absence epilepsy (JAE). We studied five JAE patients for whom MEG was recorded using a 204-channel, whole-head gradiometer system. Dynamic statistical parametric mapping (dSPM) was done to estimate the cortical source distribution of GSW. The dSPM results showed strong medial prefrontal activation in all patients, with activation in the posterior cingulate and precuneus in three of five patients simultaneously or slightly after medial prefrontal activation. Furthermore, dSPM showed that the initial activation of a GSW appears in the focal cortical regions. Cortical regions that constitute a default mode network are strongly involved in the GSW process in some patients with JAE. Results also show that focal cortical activation appears at the onset of a GSW.

  3. Physical exercise in rats with epilepsy is protective against seizures: evidence of animal studies.

    PubMed

    Arida, Ricardo Mario; Scorza, Fulvio Alexandre; Terra, Vera Cristina; Cysneiros, Roberta Monterazzo; Cavalheiro, Esper Abrão

    2009-12-01

    People with epilepsy have been discouraged from participating in physical activity due to the fear that it will exacerbate seizures. Clinical and animal studies indicate a reduction of seizure frequency as well as decrease susceptibility to subsequently evoked seizures after an exercise program. Analyses from experimental studies of animals with epilepsy submitted to physical training programs were performed. In all studies the physical training was able to reduce the number of spontaneous seizures in rats with epilepsy. Seizure occurrence during exercise was relatively absent in the majority of studies. No death was found in animals with epilepsy during 1680 h of exercise. Based on these results it is plausible encouraging persons with epilepsy to non-pharmacological treatments and preventative measures such as physical exercise.

  4. A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats.

    PubMed

    Kharatishvili, I; Nissinen, J P; McIntosh, T K; Pitkänen, A

    2006-06-30

    Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66+/-37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies.

  5. 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.

  6. Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy.

    PubMed

    Gower, A J; Hirsch, E; Boehrer, A; Noyer, M; Marescaux, C

    1995-11-01

    The anticonvulsant effects of levetiracetam were assessed in two genetic rat models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and tonic-clonic convulsions. In the GAERS model of petit mal epilepsy, levetiracetam markedly suppressed spontaneous spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The effects were already marked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produced no observable effects on behaviour apart from slight reversible sedation at 170 mg/kg. In contrast, piracetam, a structural analogue of levetiracetam, significantly and consistently suppressed SWD in GAERS rats only at the high dose of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam appeared to be due to increased sleeping rather than to a direct antiepileptic effect. The results with levetiracetam argue for a clinical application in both petit mal, absence epilepsy and in treating generalised tonic-clonic and partial seizures.

  7. Anticonvulsant effect of piperine ameliorates memory impairment, inflammation and oxidative stress in a rat model of pilocarpine-induced epilepsy

    PubMed Central

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

    2017-01-01

    The primary active component of black pepper is piperine, which is purified and used to treat epilepsy, achieving higher efficiency when purified. The present study was conducted to evaluate whether the anticonvulsant effect of piperine ameliorates pilocarpine-induced epilepsy, and to investigate the mechanism underlying these effects. Epilepsy was induced in Sprague Dawley rats using pilocarpine. Pilocarpine-induced epilepsy in the rats was treated with 40 mg/kg piperine for 45 consecutive days. Status epilepticus and a Morris water maze test were used to analyze the anticonvulsant effects of piperine in the epileptic rats. Inflammation and oxidative stress were then measured using commercially-available kits following piperine treatment. Lastly, the activity of caspase-3 and the protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were evaluated using commercially-available kits and western blot analysis, respectively. The results demonstrated that treatment with piperine was able to reduce the status epilepticus and prevented memory impairment following pilocarpine-induced epilepsy in rats. The anticonvulsant effects of piperine decreased inflammation and oxidative stress following pilocarpine-induced epilepsy in rats. The upregulated activity of caspase-3 and expression levels of Bax/Bcl-2 were suppressed following treatment with piperine in the rats with pilocarpine-induced epilepsy. These results suggest that the anticonvulsant effects of piperine ameliorate memory impairment, inflammation and oxidative stress in a rat model of pilocarpine-induced epilepsy. PMID:28352353

  8. Diminished presynaptic GABA(B) receptor function in the neocortex of a genetic model of absence epilepsy.

    PubMed

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

    2009-01-01

    Changes in GABA(B) 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 downregulating the function of presynaptic GABA(B) 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 GABA(B) receptor agonist baclofen (0.1-10 microM) 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 GABA(B) receptors in the WAG/Rij rat neocortex. We propose that this alteration may contribute to neocortical hyperexcitability and thus to absence seizures.

  9. Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

    PubMed

    de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Lopim, Glauber Menezes; Vannucci Campos, Diego; Fernandes, Jansen; Cabral, Francisco Romero; Arida, Ricardo Mario

    2017-04-01

    Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.

  10. 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

  11. Amygdala opioid receptors mediate the electroacupuncture-induced deterioration of sleep disruptions in epilepsy rats

    PubMed Central

    2013-01-01

    Background Clinical and experimental evidence demonstrates that sleep and epilepsy reciprocally affect each other. Previous studies indicated that epilepsy alters sleep homeostasis; in contrast, sleep disturbance deteriorates epilepsy. If a therapy possesses both epilepsy suppression and sleep improvement, it would be the priority choice for seizure control. Effects of acupuncture of Feng-Chi (GB20) acupoints on epilepsy suppression and insomnia treatment have been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot). Therefore, this study was designed to investigate the effect of electroacupuncture (EA) stimulation of bilateral Feng-Chi acupoints on sleep disruptions in rats with focal epilepsy. Results Our result indicates that administration of pilocarpine into the left central nucleus of amygdala (CeA) induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep. High-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints, in which a 30-min EA stimulation was performed before the dark period of the light:dark cycle in three consecutive days, further deteriorated pilocarpine-induced sleep disruptions. The EA-induced exacerbation of sleep disruption was blocked by microinjection of naloxone, μ- (naloxonazine), κ- (nor-binaltorphimine) or δ-receptor antagonists (natrindole) into the CeA, suggesting the involvement of amygdaloid opioid receptors. Conclusion The present study suggests that high-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints exhibits no benefit in improving pilocarpine-induced sleep disruptions; in contrast, EA further deteriorated sleep disturbances. Opioid receptors in the CeA mediated EA-induced exacerbation of sleep disruptions in epileptic rats. PMID:24215575

  12. Epilepsy - children

    MedlinePlus

    Seizure disorder - children; Convulsion - childhood epilepsy; Medically refractory childhood epilepsy; Anticonvulsant - childhood epilepsy; Antiepileptic drug - childhood epilepsy; AED - childhood epilepsy

  13. A developmental study of glutamatergic neuron populations in the ventrobasal and the lateral geniculate nucleus of the thalamus: Comparing Genetic Absence Rats from Strasbourg (GAERS) and normal control wistar rats.

    PubMed

    Kirazlı, Özlem; Çavdar, Safiye; Yıldızel, Sercan; Onat, Filiz; Kaptanoğlu, Erkan

    2017-02-01

    An imbalance of GABAergic inhibition and glutamatergic excitation is suspected to be the cause of absence epileptic seizures. Absence seizures are known to be generated in thalamocortical circuitry. In the present study we used light microscopy immunohistochemistry to quantify the density of glutamate+ve neurons at two developmental stages (P10 and P60) in two thalamic nuclei, the ventrobasal (VB) and lateral geniculate nucleus (LGN) in Wistar rats and compared the results with similar data obtained from genetic absence epilepsy rats from Strasbourg (GAERS). Rats were perfused transcardially with glutaraldehyde and paraformaldehyde fixative, then samples from VB and LGN were removed from each animal and sectioned. The glutamatergic neurons were labelled using light-microscopic glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in VB and LGN of GAERS and Wistar rats. The data were statistically analyzed. The distribution of the glutamate+ve neurons in the VB thalamic nucleus showed a significant reduction in the neuronal profiles per unit thalamic area from P10 to P60 in both Wistar and GAERS. The decrease was greater in the GAERS compared to the Wistar animals. However, in the LGN no reduction was observed either in the Wistar or in the GAERS. Comparing the density of glutamate+ve neurons in the VB thalamic nucleus of P10 of Wistar animals with of P10 GAERS showed statistically significant greater densities of these neurons in GAERS than in the Wistar rats. However no significant difference was present at P60 between the Wistar and GAERS animals. The disproportional decrease in GAERS may be related to the onset of absence seizures or may be related to neurogenesis of absence epilepsy.

  14. PICK1 uncoupling from mGluR7a causes absence-like seizures.

    PubMed

    Bertaso, Federica; Zhang, Chuansheng; Scheschonka, Astrid; de Bock, Frédéric; Fontanaud, Pierre; Marin, Philippe; Huganir, Richard L; Betz, Heinrich; Bockaert, Joël; Fagni, Laurent; Lerner-Natoli, Mireille

    2008-08-01

    Absence epilepsy is a neurological disorder that causes a recurrent loss of consciousness and generalized spike-and-wave discharges on an electroencephalogram (EEG). The role of metabotropic glutamate receptors (mGluRs) and associated scaffolding proteins in absence epilepsy has been unclear to date. We investigated a possible role for these proteins in absence epilepsy, focusing on the mGluR7a receptor and its PDZ-interacting protein, protein interacting with C kinase 1 (PICK1), in rats and mice. Injection of a cell-permeant dominant-negative peptide or targeted mutation of the mGluR7a C terminus, both of which disrupt the interaction between the receptor and PDZ proteins, caused behavioral symptoms and EEG discharges that are characteristic of absence epilepsy. Inactivation of the Pick1 gene also facilitated pharmacological induction of the absence epilepsy phenotype. The cortex and thalamus, which are known to participate in absence epilepsy, were involved, but the hippocampus was not. Our results indicate that disruption of the mGluR7a-PICK1 complex is sufficient to induce absence epilepsy-like seizures in rats and mice, thus providing, to the best of our knowledge, the first animal model of metabotropic glutamate receptor-PDZ protein interaction in absence epilepsy.

  15. 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

  16. 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.

  17. Absence of anticipatory contrast in rats trained on multiple schedules.

    PubMed Central

    Williams, B A

    1990-01-01

    Rats were trained on three- and four-component multiple schedules in which two of the components were correlated with identical reinforcement schedules that remained unchanged throughout training. These target components differed in terms of whether their respective following schedules were either higher or lower in value. Unlike corresponding experiments previously reported with pigeons, higher response rates occurred in the target component followed by a higher valued schedule than in the target component followed by the lower valued schedule. Overall contrast effects occurred independently of these sequential effects, but were inconsistent across subjects. The results suggest that the effects of a following schedule of reinforcement are opposite for pigeons and rats, and that one reason previous studies have often failed to show contrast effects with rats is that the effects of the following schedule in rats are in competition with contrast dynamics. PMID:2341822

  18. Abnormal Expression of FBXL20 in Refractory Epilepsy Patients and a Pilocarpine-Induced Rat Model.

    PubMed

    Fu, Pengfei; Wen, YueTao; Xiong, Yan; Zhang, Yanke; Zhang, Haiyang; Xie, Yanfeng; Shi, Quanhong

    2016-11-01

    E3 ubiquitin ligases are important protein-modifying enzymes involved in the pathogenesis of a variety of neurodegenerative diseases. F-box and leucine-rich repeat protein 20 (FBXL20), an E3 ubiquitin ligase widely expressed in the central nervous system, plays an important role in the ubiquitin-dependent degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an important factor in the release of synaptic vesicles. FBXL20 has been associated with a variety of neurodegenerative diseases; thus, we hypothesized that FBXL20 is involved in the development of epilepsy. Herein, we used immunofluorescence staining, immunohistochemistry and western blotting to determine the expression pattern of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced epilepsy animal models. We also injected SD rats with lentivirus-vector mediated overexpression of FBXL20. The results showed that FBXL20 is expressed in the membrane and the cytoplasm of cortical neurons, and overexpression of FBXL20 decreased the onset level of spontaneous seizure, the frequency and duration of seizures. Additionally, FBXL20 protein level was decreased but RIM1 protein level was increased in the epileptic group compared with the LV-FBXL20 and LV-GFP group. These findings in humans were consistent with the results from a pilocarpine-induced animal model of chronic epilepsy. Thus, abnormal expression of FBXL20 might play an important role in the development of epilepsy.

  19. BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats.

    PubMed

    Kuramoto, Satoshi; Yasuhara, Takao; Agari, Takashi; Kondo, Akihiko; Jing, Meng; Kikuchi, Yoichiro; Shinko, Aiko; Wakamori, Takaaki; Kameda, Masahiro; Wang, Feifei; Kin, Kyohei; Edahiro, Satoru; Miyoshi, Yasuyuki; Date, Isao

    2011-01-12

    Brain-derived neurotrophic factor (BDNF) is a well neurotrophic factor with neuroprotective potentials for various diseases in the central nervous system. However several previous studies demonstrated that BDNF might deteriorate symptoms for epilepsy model of animals by progression of abnormal neurogenesis. We hypothesized that continuous administration of BDNF at low dose might be more effective for epilepsy model of animals because high dose of BDNF was used in many studies. BDNF-secreting cells were genetically made and encapsulated for transplantation. Rats receiving BDNF capsule showed significant amelioration of seizure stage and reduction of the number of abnormal spikes at 7 days after kainic acid administration, compared to those of control group. The number of BrdU and BrdU/doublecortin positive cells in the hippocampus of BDNF group significantly increased, compared to that of control group. NeuN positive cells in the CA1 and CA3 of BDNF group were significantly preserved, compared to control group. In conclusion, low dose administration using encapsulated BDNF-secreting cells exerted neuroprotective effects with enhanced neurogenesis on epilepsy model of rats. These results might suggest the importance of the dose and administrative way of this neurotrophic factor to the epilepsy model of animals.

  20. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    PubMed

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-01-09

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H2O2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  1. Ethosuximide Affects Paired-Pulse Facilitation in Somatosensory Cortex of WAG\\Rij Rats as a Model of Absence Seizure

    PubMed Central

    Ghamkhari Nejad, Ghazaleh; Shahabi, Parviz; Alipoor, Mohamad Reza; Ghaderi Pakdel, Firouz; Asghari, Mohammad; Sadighi Alvandi, Mina

    2015-01-01

    Purpose: The interaction between somatosensory cortex and thalamus via a thalamocortical loop is a theory behind induction of absence epilepsy. Inside peri-oral somatosensory (S1po) and primary somatosensory forelimb (S1fl) regions, excitatory and inhibitory systems are not balanced and GABAergic inhibitory synapses seem to play a fundamental role in short-term plasticity alterations. Methods: We investigated the effects of Ethosuximide on presynaptic changes by utilizing paired-pulse stimulation that was recorded from somatosensory cortex in 18 WAG\\Rij rats during epileptic activity. A twisted tripolar electrode including two stimulating electrodes and one recording electrode was implanted into the S1po and S1FL according to stereotaxic landmarks. Paired-pulses (200 µs, 100-1000 µA, 0.1 Hz) were applied to somatosensory cortex at 50, 100, 400, 500 ms inter-pulse intervals for 50 min period. Results: The results showed that paired-pulse facilitation was significantly reduced at all intervals in all times, but compared to the control group of epileptic WAG/Rij rats (p<0.05), it was exceptional about the first 10 minutes after the injection. At the intervals of 50 and 100 ms, a remarkable PPD was found in second, third, fourth and fifth 10-min post injection. Conclusion: These experiments indicate that Ethosuximide has effects on presynaptic facilitation in somatosensory cortex inhibitory loops by alteration in GABA levels that leads to a markedly diminished PPF in paired-pulse stimulation. PMID:26819920

  2. Altered expression of c-Abl in patients with epilepsy and in a rat model.

    PubMed

    Chen, Ling; Wang, Zhihua; Tang, Bo; Fang, Min; Li, Jie; Chen, Guojun; Wang, Xuefeng

    2014-07-01

    c-Abl is an ubiquitous nonreceptor tyrosine kinase involved in signal transduction pathways that promote cytoskeleton remodeling and apoptosis. In brain, c-Abl plays important roles in neuronal development, neurogenesis, neuronal migration, neurite outgrowth, and synaptic plasticity. Neuronal death, gliosis and synaptic remodeling are thought to be involved in the development of epilepsy. Here we investigated the expression pattern and distribution of total and phosphorylated c-Abl in patients with temporal lobe epilepsy (TLE) and a rat model of epilepsy to explore the probable relationship between c-Abl expression and TLE. Double immunolabeling, Immunohistochemistry, and immunoblotting results showed that both total and phosphorylated c-Abl were upregulated in the temporal neocortex of 26 patients with TLE compared to nonepileptic controls. In the temporal neocortex of pilocarpine-treated rats, upregulation of total and phosphorylated c-Abl began 6 hours after seizures, with relatively high expression for 60 days. In the hippocampus of experimental rats, total unphosphorylated c-Abl elevated from 6 hours to 30 days after seizures, the expression then returned to normal levels at 60 days, while phosphorylated c-Abl increased along with the time and maintained at significant high levels for up to 60 days. These results indicate that c-Abl may play an important role in the development of TLE.

  3. 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.

  4. Occurrence of Epilepsy at Different Zeitgeber Times Alters Sleep Homeostasis Differently in Rats

    PubMed Central

    Yi, Pei-Lu; Chen, Ying-Ju; Lin, Chung-Tien; Chang, Fang-Chia

    2012-01-01

    Study Objectives: Controversial sleep disruptions (e.g., poor nighttime sleep and daytime somnolence) are common in epilepsy patients. Sleep is known to be regulated by homeostatic factors, which mediate sleep propensity, and the circadian oscillator, a clocklike mechanism. However, it is unknown how epileptic episodes that occur at different zeitgeber times (ZTs) alter sleep regulation. This study was designed to elucidate the sleep disruptions associated with epilepsy and their underlying mechanisms by delivering kindled epilepsy at different ZTs: ZT0, ZT6, and ZT13. Design: Kindled epilepsy was induced at 3 different ZTs, and sleep-wake activities were analyzed before and after full-blown seizure. Ribonuclease protection assay, radioimmunoassay, and immunohistochemistry were respectively employed to determine the levels of interleukin-1 mRNA, corticosterone, and PER1 protein. Setting: The experiments were performed at Neurophysiology Laboratory at National Taiwan University. Participant and Interventions: Male Sprague-Dawley rats were implanted with electroencephalograph (EEG) electrodes, a bipolar stimulating electrode, and a guide cannula. Kindling stimuli were delivered via a bipolar electrode placed in the right central nucleus of the amygdala. Measurement and Results: Kindled epilepsy occurring at ZT0 and ZT13 predominantly affected homeostatic factors, whereas ZT6-kindling stimuli altered the circadian oscillator. ZT0-kindling decreased rapid eye movement (REM) and non-REM (NREM) sleep, which was mediated by corticotrophin-releasing hormone, but did not alter the rhythm of sleep-wake fluctuation. On the other hand, ZT13-kindling enhanced interleukin-1 and consequently increased NREM sleep without altering the sleep-wake fluctuation. Nevertheless, the expression of PER1 protein in suprachiasmatic nucleus of the hypothalamus and the circadian rhythm of sleep fluctuation were respectively advanced 6 h and 2 h when kindling stimulation was delivered at ZT6

  5. Phenotypic characterization of spontaneously mutated rats showing lethal dwarfism and epilepsy.

    PubMed

    Suzuki, Hiroetsu; Takenaka, Motoo; Suzuki, Katsushi

    2007-08-01

    We have characterized the phenotype of spontaneously mutated rats, found during experimental inbreeding in a closed colony of Wistar Imamichi rats. Mutant rats showed severe dwarfism, short lifespan (early postnatal lethality), and high incidence of epileptic seizures. Mutant rats showed growth retardation after 3 d of age, and at 21 d their weight was about 56% that of normal rats. Most mutant rats died without reaching maturity, and 95% of the mutant rats had an ataxic gait. About 34% of the dwarf rats experienced epileptic seizures, most of which started as 'wild running' convulsions, progressing to generalized tonic-clonic convulsions. At age 28 d, the relative weight of the testes was significantly lower, and the relative weight of the brain was significantly higher, in mutant than in normal rats. Histologically, increased apoptotic germ cells, lack of spermatocytes, and immature Leydig cells were found in the mutant testes, and extracellular vacuoles of various sizes were present in the hippocampus and amygdala of the mutant brain. Mutant rats had significantly increased concentrations of plasma urea nitrogen, creatinine, and inorganic phosphate, as well as decreased concentrations of plasma growth hormone. Hereditary analysis showed that the defects were inherited as a single recessive trait. We have named the hypothetically mutated gene as lde (lethal dwarfism with epilepsy).

  6. Low Frequency Stimulation of Hippocampal Commissures Reduces Seizures in Chronic Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Rashid, Saifur; Pho, Gerald; Czigler, Michael; Werz, Mary Ann; Durand, Dominique M.

    2013-01-01

    SUMMARY Purpose To investigate the effects of low frequency stimulation (LFS) of a fiber track for the suppression of spontaneous seizures described by Nissinen in a rat model of human temporal lobe epilepsy. Methods Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recordings electrodes were placed in the CA3 regions bilaterally and neural data was recorded for a minimum of six weeks. LFS (60 minute train of 1Hz biphasic square wave pulses, each 0.1ms in duration and 200μA in amplitude, followed by 15 minutes of rest) was applied to the VHC for, two weeks, 24 hours a day. Key Findings The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n=7). By the end of the two-week period of stimulation, there was a significant 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during two weeks LFS session. The hippocampal histological analysis showed no significant difference between rats that received LFS and SE-induction and those that had only received SE-induction. None of the animals showed any symptomatic hemorrhage, infection or complication. Significance LFS applied at a frequency of 1Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could be lead to the development of the new therapeutic modality for human patients with temporal lobe epilepsy. PMID:22150779

  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.

  8. Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs.

    PubMed

    De Sarro, Giovambattista; Russo, Emilio; Citraro, Rita; Meldrum, Brian S

    2015-08-06

    This review summarizes the current knowledge about DBA/2 mice and genetically epilepsy-prone rats (GEPRs) and discusses the contribution of such animal models on the investigation of possible new therapeutic targets and new anticonvulsant compounds for the treatment of epilepsy. Also, possible chemical or physical agents acting as proconvulsant agents are described. Abnormal activities of enzymes involved in catecholamine and serotonin synthesis and metabolism were reported in these models, and as a result of all these abnormalities, seizure susceptibility in both animals is greatly affected by pharmacological manipulations of the brain levels of monoamines and, prevalently, serotonin. In addition, both genetic epileptic models permit the evaluation of pharmacodynamic and pharmacokinetic interactions among several drugs measuring plasma and/or brain level of each compound. Audiogenic models of epilepsy have been used not only for reflex epilepsy studies, but also as animal models of epileptogenesis. The seizure predisposition (epileptiform response to sound stimulation) and substantial characterization of behavioral, cellular, and molecular alterations in both acute and chronic (kindling) protocols potentiate the usefulness of these models in elucidating ictogenesis, epileptogenesis, and their mechanisms. This article is part of a Special Issue entitled "Genetic Models-Epilepsy".

  9. Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure.

    PubMed

    Hanaya, R; Hosoyama, H; Sugata, S; Tokudome, M; Hirano, H; Tokimura, H; Kurisu, K; Serikawa, T; Sasa, M; Arita, K

    2012-09-27

    The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.

  10. Genetically Epilepsy-Prone Rats Have Increased Brain Regional Activity of an Enzyme Which Liberates Glutamate from N-acetyl-aspartyl-glutamate

    DTIC Science & Technology

    1992-01-01

    genetically epilepsy -prone iats "was 11-26% greater than control in brain regions, including the amygdala, hippocarrpus and cerebellum, as well as the...9 -0 3 Genetically epilepsy -prone rats have increased brain regional activity of an enzyme which liberates glutamate from N-acetyl-aspartyl...in genctically epilepsy -prone rats was 11-~261; greater than control in brain regions. including the amygdala. hippocampus and cerebellum, as well as

  11. Gelastic epilepsy

    PubMed Central

    Gumpert, John; Hansotia, Phiroze; Upton, Adrian

    1970-01-01

    A case of retinitis pigmentosa with laughing epilepsy is described. Stereotyped repetitive episodes of limb movement, rigidity, and cackling laughter responding to diazepam are recorded. One episode is presented as gelastic status epilepticus and the clinical and EEG features are reported. Features of gelastic epilepsy are discussed and briefly compared with other laughing disorders. A short history of the condition is accompanied by a relevant review of the literature. The possible importance of hypothalamic lesions in laughing epilepsy is discussed and the absence of consistent EEG findings is noted. Images PMID:5505675

  12. Abnormal expression of netrin-G2 in temporal lobe epilepsy neurons in humans and a rat model.

    PubMed

    Pan, Yumin; Liu, Guangwei; Fang, Min; Shen, Lan; Wang, Liang; Han, Yanbing; Shen, Dinglie; Wang, Xuefeng

    2010-08-01

    The membrane-bound axon guidance molecule netrin-g2 is preferentially expressed in the central nervous system and plays a role in synapse formation and maintenance. Using immunohistochemistry, immunofluorescence, and Western blotting, we investigated the possible correlation between netrin-g2 expression and intractable epilepsy (IE) using surgical samples from epilepsy patients. We used 35 samples of temporal neocortex from patients undergoing surgery for drug-refractory epilepsy and 15 autopsy samples from individuals who died in traffic accidents (i.e., samples of normal human brain). We also examined netrin-g2 expression in the hippocampus and adjacent cortex of rats with temporal lobe epilepsy (lithium chloride-pilocarpine model). Netrin-g2 was expressed in the membrane and cytoplasm of neurons from control specimens, and expression was higher in tissue from patients with intractable epilepsy. Western blotting of rat brain tissue showed that netrin-g2 was upregulated starting at 6h after kindling. Maximal expression was seen around 2 days, and relatively high expression was maintained until 30 days. Expression then returned to normal levels at 60 days, which was consistent with the immunohistochemical and immunofluorescence results. These data implicate netrin-g2 in the pathophysiology of epilepsy and are consistent with the hypothesis that this protein may participate in the abnormal development of synapses and in neuron migration.

  13. 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.

  14. The Anticonvulsant and Antioxidant Effects of Berberine in Kainate-induced Temporal Lobe Epilepsy in Rats

    PubMed Central

    Mojarad, Tourandokht Baluchnejad; Roghani, Mehrdad

    2014-01-01

    Introduction Temporal lobe epilepsy (TLE) is a long lasting neurological disorder in which patients suffer from spontaneous seizures. New treatments with novel mechanisms of action are needed to help those patients whose seizures are resistant to available drugs. In this study, we investigated the possible neuroprotective effect of berberine in an intrahippocampal kainate model of TLE in rat. Methods In the present study, the anticonvulsant and antioxidant effects of intraperitoneal administration of berberine (25, 50 and 100 mg/kg), was evaluated in intrahippocampal kainate (4µg)-induced TLE in rats. Results The results showed that the kainate rats exhibit acute and spontaneous seizures in 24 hours and two weeks after intrahippocampal kainic acid injection. Administration of berberine, significantly decreased the Racine score and rate of incidence of seizure in kainate rats (P<0.05). On the other hand, berberine ameliorated the lipid peroxidation (P<0.001) and nitrite (P<0.001) level, but had no effect on SOD activity. Discussion These data suggest that berberine pretreatment could attenuate spontaneous recurrent seizures. Since, administration of berberine decreased lipid peroxidation in kainate rats, it seems that berberine favorable effect is due to its effectiveness in lessening of oxidative stress in rat. PMID:25337370

  15. 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

  16. Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide A.

    PubMed

    Soman, Smijin; Anju, T R; Jayanarayanan, S; Antony, Sherin; Paulose, C S

    2013-06-01

    The aim of this study was to investigate the effect of Withania somnifera (WS) extract, withanolide A (WA), and carbamazepine (CBZ) on cerebellar AMPA receptor function in pilocarpine-induced temporal lobe epilepsy (TLE). In the present study, motor learning deficit was studied by rotarod test, grid walk test, and narrow beam test. Motor learning was significantly impaired in rats with epilepsy. The treatment with WS and WA significantly reversed the motor learning deficit in rats with epilepsy when compared with control rats. There was an increase in glutamate content and IP3 content observed in rats with epilepsy which was reversed in WS- and WA-treated rats with epilepsy. alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor dysfunction was analyzed using radiolabeled AMPA receptor binding assay, AMPA receptor mRNA expression, and immunohistochemistry using anti-AMPA receptor antibody. Our results suggest that there was a decrease in Bmax, mRNA expression, and AMPA receptor expression indicating AMPA receptor dysfunction, which is suggested to have contributed to the motor learning deficit observed in rats with epilepsy. Moreover, treatment with WS and WA resulted in physiological expression of AMPA receptors. There was also alteration in GAD and GLAST expression which supplemented the increase in extracellular glutamate. The treatment with WS and WA reversed the GAD and GLAST expression. These findings suggest that WS and WA regulate AMPA receptor function in the cerebellum of rats with TLE, which has therapeutic application in epilepsy.

  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

    2015-12-02

    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.

  18. Reproductive success of bromadiolone-resistant rats in absence of anticoagulant pressure.

    PubMed

    Heiberg, Ann-Charlotte; Leirs, Herwig; Siegismund, Hans R

    2006-09-01

    Resistance to anticoagulant rodenticides in brown rats (Rattus norvegicus Berk.) is associated with pleiotropic effects, notably with an increased dietary vitamin K requirement. Owing to this disadvantage, resistance is believed to be selected against if anticoagulant selection is absent. In small experimental populations of wild brown rats, an investigation was carried out to establish whether tolerance to anticoagulant exposure changed over a period of 2 years. In the same populations, DNA microsatellite markers were used to infer parentage, and this made it possible to estimate reproductive success of sensitive and resistant rats and estimate effective population size, Ne. Even though there was evidence for a selection against resistant rats with high vitamin K requirement, anticoagulant tolerance was not seen to be significantly influenced in the absence of bromadiolone selection. As the population size under investigation was small, random genetic drift may have played a role in this. In the presence of bromadiolone selection, however, the tolerance was significantly increased, suggesting that continuous selection will increase the proportion of highly resistant rats in the population. It was found that, for both males and females, surprisingly few individuals contributed to the next generation with numerous offspring, and most breeders contributed with none or a single offspring. The expected higher reproductive success and consequent increase in proportional numbers of sensitive rats in the absence of anticoagulant selection could not be observed. Among the resistant rats, moderately resistant females were found to be better breeders than highly resistant breeders, but for resistant males the reverse was true. This could be explained by the fact that the increased vitamin K requirement results in sex differential selection; in highly resistant males the selection presumably takes place at the immature stage, whereas in females the vitamin K requirement

  19. Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study.

    PubMed

    Camfield, P R; Camfield, C S; Dooley, J M; Gordon, K; Jollymore, S; Weaver, D F

    1992-05-01

    There are anecdotal reports of increased seizures in humans after ingestion of aspartame. We studied 10 children with newly diagnosed but untreated generalized absence seizures. Ambulatory cassette recording of EEG allowed quantification of numbers and length of spike-wave discharges in a double-blind study on two consecutive days. On one day the children received 40 mg/kg aspartame and on the other day, a sucrose-sweetened drink. Baseline EEG was the same before aspartame and sucrose. Following aspartame compared with sucrose, the number of spike-wave discharges per hour and mean length of spike-wave discharges increased but not to a statistically significant degree. However, the total duration of spike-wave discharge per hour was significantly increased after aspartame (p = 0.028), with a 40% +/- 17% (SEM) increase in the number of seconds per hour of EEG recording that the children spent in spike-wave discharge. Aspartame appears to exacerbate the amount of EEG spike wave in children with absence seizures. Further studies are needed to establish if this effect occurs at lower doses and in other seizure types.

  20. 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.

  1. Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models.

    PubMed

    Motamedi, Gholam K; Salazar, Patricia; Smith, Eric L; Lesser, Ronald P; Webber, William R S; Ortinski, Pavel I; Vicini, Stefano; Rogawski, Michael A

    2006-08-01

    Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling to abort spontaneous epileptiform discharges in in vitro brain slice models. We induced spontaneous epileptiform activity in rat brain slices by exposure to 4-aminopyridine (4-AP), 4-AP plus bicuculline, and Mg(2+)-free artificial CSF (aCSF) at 28-34 degrees C. Extracellular field recordings were made at hippocampal or neocortical sites. Slice temperature was reduced by perfusion with cold aCSF. Rapid cooling at rates of 2-5 degrees C/s was compared to cooling at slower rates of 0.1-1 degrees C/s. Cooling at both rates reversibly aborted epileptiform discharges in all three models and at all recording sites. With rapid cooling, small temperature drops were highly effective in terminating discharges, an effect that was sustained for as long as the reduced temperature level was maintained. In contrast, slow cooling required much larger temperature drops to inhibit discharges. With slow cooling, absolute temperature drops to 21-22 degrees C caused a 90% reduction in event frequency, but cooling to 14-15 degrees C was required to terminate discharges. We conclude that rapid cooling as effectively aborts discharges in in vitro epilepsy models as does slow cooling, but the magnitude of the temperature change required is less. Practical devices to inhibit seizure activity may only need to induce small temperature drops, if the cooling can be applied sufficiently rapidly.

  2. Cingulate Epilepsy

    PubMed Central

    Alkawadri, Rafeed; So, Norman K.; Van Ness, Paul C.; Alexopoulos, Andreas V.

    2016-01-01

    present with electroclinical findings that are suggestive of temporal lobe epilepsy and can be considered as another example of pseudotemporal epilepsies. The electroclinical presentation and surgical outcome of lesional anterior cingulate epilepsy is possibly influenced by the underlying pathology. This study highlights the difficulty in localizing seizures arising from the cingulate gyrus in the absence of a magnetic resonance image lesion. PMID:23753910

  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. 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.

  5. 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.

  6. Increased expression of histone deacetylases 2 in temporal lobe epilepsy: a study of epileptic patients and rat models.

    PubMed

    Huang, Yuanyuan; Zhao, Fenghua; Wang, Liang; Yin, Huan; Zhou, Chunlei; Wang, Xuefeng

    2012-02-01

    Histone deacetylases 2 (HDAC2) is expressed in the central nervous system; it has multiple functions in neural plasticity. However, we do not know if HDAC2 is also involved in the pathology of epilepsy. Here we report that HDAC2 was expressed in the brain tissues of both control and temporal lobe epilepsy (TLE) patients. Results from immunofluorescence and immunohistochemistry showed that HDAC2 was primarily located in the nucleus and that TLE patients exhibit significantly more HDAC2 positive cells than control. Western blotting showed that HDAC2 protein levels were significantly higher in TLE than in control brain. Moreover, in the rat model of TLE, there was a sustained enhancement of HDAC2 expression in rat models of TLE. HDAC2 was significantly increased in both the acute (1 day) and chronic (60 days) animals compared with control group. These results suggest that HDAC2 play an important role in the pathogenesis of human TLE.

  7. Protein expression of phospho-lim kinase-1 in patients and an experimental rat model with intractable temporal lobe epilepsy

    PubMed Central

    Huang, Hao; Wang, Heng; Yuan, Jinxian; Wu, Xuling; Huang, Yunyi; Zhou, Xin; Chen, Yangmei

    2015-01-01

    Lim kinase-1 (LIMK1) plays a critical role in dendritic spine morphogenesis and brain function. The protein expression pattern of phospho-LIMK1 (p-LIMK1), the active form of LIMK1, in intractable temporal lobe epilepsy (TLE), however, is unknown. Here we measured p-LIMK1 protein expression in thirty temporal neocortex tissue samples from intractable TLE patients, fifteen histologically normal temporal neocortex tissue samples from trauma patients without epilepsy, in the hippocampi of lithium chloride/pilocarpine-induced TLE rats, and in controls. We found that p-LIMK1 was expressed mainly in the cytoplasm of neurons. The protein expression of p-LIMK1 was significantly higher in the TLE patients and rats than in the control groups. Our results suggest that p-LIMK1 might be involved in the pathogenesis of intractable TLE. PMID:25785037

  8. Calcium Channel Dysfunction in Inferior Colliculus Neurons of the Genetically Epilepsy-Prone Rat

    PubMed Central

    N’Gouemo, Prosper; Faingold, Carl L.; Morad, Martin

    2008-01-01

    Summary Voltage-gated calcium (Ca2+) channels are thought to play an important role in epileptogenesis and seizure generation. Here, using the whole-cell configuration of patch-clamp techniques, we report on the modifications of biophysical and pharmacological properties of high threshold voltage-activated Ca2+ channel currents in inferior colliculus (IC) neurons of the genetically epilepsy-prone rats (GEPR-3s). Ca2+channel currents were measured by depolarizing pulses from a holding potential of −80 mV using barium (Ba2+) as the charge carrier. We found that the current density of high threshold voltage-activated Ca2+ channels was significantly larger in IC neurons of seizure-naive GEPR-3s compared to control Sprague-Dawley rats, and that seizure episodes further enhanced the current density in the GEPR-3s. The increased current density was reflected by both a −20 mV shifts in channel activation and a 25% increase in the non-inactivating fraction of channels in seizure-naive GEPR-3s. Such changes were reduced by seizure episodes in the GEPR-3s. Pharmacological analysis of the current density suggests that upregulation of L-, N- and R-type of Ca2+ channels may contribute to IC neuronal hyperexcitability that leads to seizure susceptibility in the GEPR-3s. PMID:19084544

  9. 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

  10. 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.

  11. A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy.

    PubMed

    Suzuki, H; Katayama, K; Takenaka, M; Amakasu, K; Saito, K; Suzuki, K

    2009-10-01

    The lde/lde rat is characterized by dwarfism, postnatal lethality, male hypogonadism, a high incidence of epilepsy and many vacuoles in the hippocampus and amygdala. We used a candidate approach to identify the gene responsible for the lde phenotype and assessed the susceptibility of lde/lde rats for audiogenic seizures. Following backcross breeding of lethal dwarfism with epilepsy (LDE) to Brown Norway rats, the lde/lde rats with an altered genetic background showed all pleiotropic phenotypes. The lde locus was mapped to a 1.5-Mbp region on rat chromosome 19 that included the latter half of the Wwox gene. Sequencing of the full-length Wwox transcript identified a 13-bp deletion in exon 9 in lde/lde rats. This mutation causes a frame shift, resulting in aberrant amino acid sequences at the C-terminal. Western blotting showed that both the full-length products of the Wwox gene and its isoform were present in normal testes and hippocampi, whereas both products were undetectable in the testes and hippocampi of lde/lde rats. Sound stimulation induced epileptic seizures in 95% of lde/lde rats, with starting as wild running (WR), sometimes progressing to tonic-clonic convulsions. Electroencephalogram (EEG) analysis showed interictal spikes, fast waves during WR and burst of spikes during clonic phases. The Wwox protein is expressed in the central nervous system (CNS), indicating that abnormal neuronal excitability in lde/lde rats may be because of a lack of Wwox function. The lde/lde rat is not only useful for understanding the multiple functions of Wwox but is also a unique model for studying the physiological function of Wwox in CNS.

  12. Absence of chemopreventive influence of propolis on the rat liver altered foci development.

    PubMed

    Said, Roueda Abou; Grassi, Tony Fernando; Scolastici, Clarissa; Alves de Lima, Rodrigo Otávio; Darros, Bruno R; Barbisan, Luis Fernando; de Camargo, João Lauro V

    2010-07-01

    Propolis (bee glue) is a complex mixture of natural substances that exhibits a broad spectrum of biological activities. As the possibility exists that it may exert a chemopreventive role against cancer development, the present study aimed to evaluate the chemopreventive influence of a Brazilian aqueous propolis extract (APE) in a rat two-stage (initiation-promotion) medium-term bioassay for chemical liver carcinogenesis. Male Wistar rats were sequentially initiated with diethylnitrosamine (DEN, 200mg/kgb.w.) and, 2 weeks later, exposed to a diet containing hexachlorobenzene (HCB, 100ppm) and to APE 0.1% through drinking water for 6 weeks. Appropriate control groups were also established. The animals were sacrificed at the weeks 8th and 30th when liver samples were processed to evaluate the development of altered hepatocyte foci (AHF) identified under hematoxylin and eosin (H&E) staining and by the immunohistochemical expression of the enzyme glutathione S-transferase placental form (GST-P). The results indicate that APE 0.1% did not protect against the development of any of the differentially identified putative preneoplastic foci in DEN-initiated animals, exposed or not to the promoting agent HCB. Also, APE 0.1% by itself did not significantly induce any AHF, what is in line with its already known absence of genotoxic potential. Our results indicate that an aqueous extract of Brazilian propolis did not exert chemoprevention on the hepatocarcinogenesis process chemically induced in the rat.

  13. Photoacoustic Imaging of Epilepsy

    DTIC Science & Technology

    2013-04-01

    Numbers 1–5 indi- cate the corresponding blood vessels in the PAT image and rat brain photograph. 241L. Xiang et al. / NeuroImage 66 (2013) 240–248( Bertram ...the epileptic circuitry have enhanced excitability throughout ( Bertram et al., 1998; Fountain et al., 1998; Mangan et al., 2000). The implication of...antiepileptic drugs after epilepsy surgery: a survey of U.S. epilepsy center neurologists. Epilepsy Behav. 10, 219–222. Bertram , E.H., 2009. Temporal lobe

  14. N-methyl-D-aspartate receptor NR2B subunit involved in depression-like behaviours in lithium chloride-pilocarpine chronic rat epilepsy model.

    PubMed

    Peng, Wei-Feng; Ding, Jing; Li, Xin; Fan, Fan; Zhang, Qian-Qian; Wang, Xin

    2016-01-01

    Depression is a common comorbidity in patients with epilepsy with unclear mechanisms. This study is to explore the role of glutamate N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunits in epilepsy-associated depression. Lithium chloride (Licl)-pilocarpine chronic rat epilepsy model was established and rats were divided into epilepsy with depression (EWD) and epilepsy without depression (EWND) subgroups based on forced swim test. Expression of NMDA receptor NR1, NR2A and NR2B subunits was measured by western blot and immunofluorescence methods. The immobility time (IMT) was significantly greater in Licl-pilocarpine model group than in Control group, which was also greater in EWD group than in EWND group. No differences of spontaneous recurrent seizure (SRS) counts over two weeks and latency were found between EWD and EWND groups. The number of NeuN positive cells was significantly less in Licl-pilocarpine model group than in Control group, but had no difference between EWD and EWND groups. The ratios of phosphorylated NR1 (p-NR1)/NR1 and p-NR2B/NR2B were significantly greater in the hippocampus in EWD group than in EWND group. Moreover, the expression of p-NR1 and p-NR2B in the CA1 subfield of hippocampus were both greater in Licl-pilocarpine model group than Control group. Selective blockage of NR2B subunit with ifenprodil could alleviate depression-like behaviours of Licl-pilocarpine rat epilepsy model. In conclusion, glutamate NMDA receptor NR2B subunit was involved in promoting depression-like behaviours in the Licl-pilocarpine chronic rat epilepsy model and might be a target for treating epilepsy-associated depression.

  15. 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.

  16. Abnormal expression of stathmin 1 in brain tissue of patients with intractable temporal lobe epilepsy and a rat model.

    PubMed

    Zhao, Fenghua; Hu, Yida; Zhang, Ying; Zhu, Qiong; Zhang, Xiaogang; Luo, Jing; Xu, Yali; Wang, Xuefeng

    2012-09-01

    Microtubule dynamics have been shown to contribute to neurite outgrowth, branching, and guidance. Stathmin 1 is a potent microtubule-destabilizing factor that is involved in the regulation of microtubule dynamics and plays an essential role in neurite elongation and synaptic plasticity. Here, we investigate the expression of stathmin 1 in the brain tissues of patients with intractable temporal lobe epilepsy (TLE) and experimental animals using immunohistochemistry, immunofluorescence and western blotting. We obtained 32 temporal neocortex tissue samples from patients with intractable TLE and 12 histologically normal temporal lobe tissues as controls. In addition, 48 Sprague Dawley rats were randomly divided into six groups, including one control group and five groups with epilepsy induced by lithium chloride-pilocarpine. Hippocampal and temporal lobe tissues were obtained from control and epileptic rats on Days 1, 7, 14, 30, and 60 after kindling. Stathmin 1 was mainly expressed in the neuronal membrane and cytoplasm in the human controls, and its expression levels were significantly higher in patients with intractable TLE. Moreover, stathmin 1 was also expressed in the neurons of both the control and the experimental rats. Stathmin 1 expression was decreased in the experimental animals from 1 to 14 days postseizure and then significantly increased at Days 30 and 60 compared with the control group. Many protruding neuronal processes were observed in the TLE patients and in the chronic stage epileptic rats. These data suggest that stathmin 1 may participate in the abnormal network reorganization of synapses and contribute to the pathogenesis of TLE.

  17. Epilepsy - resources

    MedlinePlus

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

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

    PubMed

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

    2017-02-01

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

  20. MBD3 expression and DNA binding patterns are altered in a rat model of temporal lobe epilepsy

    PubMed Central

    Bednarczyk, Joanna; Dębski, Konrad J.; Bot, Anna M.; Lukasiuk, Katarzyna

    2016-01-01

    The aim of the present study was to examine involvement of MBD3 (methyl-CpG-binding domain protein 3), a protein involved in reading DNA methylation patterns, in epileptogenesis and epilepsy. We used a well-characterized rat model of temporal lobe epilepsy that is triggered by status epilepticus, evoked by electrical stimulation of the amygdala. Stimulated and sham-operated animals were sacrificed 14 days after stimulation. We found that MBD3 transcript was present in neurons, oligodendrocytes, and astrocytes in both control and epileptic animals. We detected the nuclear localization of MBD3 protein in neurons, mature oligodendrocytes, and a subpopulation of astrocytes but not in microglia. Amygdala stimulation significantly increased the level of MBD3 immunofluorescence. Immunoprecipitation followed by mass spectrometry and Western blot revealed that MBD3 in the adult brain assembles the NuRD complex, which also contains MTA2, HDAC2, and GATAD2B. Using chromatin immunoprecipitation combined with deep sequencing, we observed differences in the occupancy of DNA regions by MBD3 protein between control and stimulated animals. This was not followed by subsequent changes in the mRNA expression levels of selected MBD3 targets. Our data demonstrate for the first time alterations in the MBD3 expression and DNA occupancy in the experimental model of epilepsy. PMID:27650712

  1. PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy

    PubMed Central

    2012-01-01

    Background Recently, inflammatory cascades have been suggested as a target for epilepsy therapy. Positron emission tomography (PET) imaging offers the unique possibility to evaluate brain inflammation longitudinally in a non-invasive translational manner. This study investigated brain inflammation during early epileptogenesis in the post-kainic acid-induced status epilepticus (KASE) model with post-mortem histology and in vivo with [18F]-PBR111 PET. Methods Status epilepticus (SE) was induced (N = 13) by low-dose injections of KA, while controls (N = 9) received saline. Translocator protein (TSPO) expression and microglia activation were assessed with [125I]-CLINDE autoradiography and OX-42 immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [18F]-PBR111 PET imaging with metabolite-corrected input function was performed before post-mortem evaluation. [18F]-PBR111 volume of distribution (Vt) in volume of interests (VOIs) was quantified by means of kinetic modelling and a VOI/metabolite-corrected plasma activity ratio. Results Animals with substantial SE showed huge overexpression of TSPO in vitro in relevant brain regions such as the hippocampus and amygdala (P < 0.001), while animals with mild symptoms displayed a smaller increase in TSPO in amygdala only (P < 0.001). TSPO expression was associated with OX-42 signal but without obvious cell loss. Similar in vivo [18F]-PBR111 increases in Vt and the simplified ratio were found in key regions such as the hippocampus (P < 0.05) and amygdala (P < 0.01). Conclusion Both post-mortem and in vivo methods substantiate that the brain regions important in seizure generation display significant brain inflammation during epileptogenesis in the KASE model. This work enables future longitudinal investigation of the role of brain inflammation during epileptogenesis and evaluation of anti-inflammatory treatments. PMID:23136853

  2. An Abnormal GABAergic System in the Inferior Colliculus Provides a Basis for Audiogenic Seizures in Genetically Epilepsy-Prone Rats

    PubMed Central

    Ribak, Charles E.

    2015-01-01

    In this review of neuroanatomical studies of the genetically epilepsy-prone rat (GEPR), three main topics will be covered. First, the number of GABAergic neurons and total neurons in the inferior colliculus of GEPRs will be compared to those of the non-epileptic Sprague-Dawley rat. Next, the number of small neurons in the inferior colliculus will be described in both developmental and genetic analyses of GEPRs and their backcrosses. Last, results from two types of studies on the propagation pathways for audiogenic seizures in GEPRs will be shown. Together, these studies demonstrate a unique GABAergic, small neuron defect in the inferior colliculus of GEPRs that may play a vital role in the initiation and spread of seizure activity during audiogenic seizures. PMID:25812940

  3. Anatomical changes of the GABAergic system in the inferior colliculus of the genetically epilepsy-prone rat.

    PubMed

    Roberts, R C; Ribak, C E

    1986-09-01

    The number of GABAergic neurons as determined by GAD immunocytochemistry and total neurons as determined from Nissl preparations were counted and classified at the light microscopic level in the inferior colliculus (IC) of the genetically epilepsy prone rat (GEPR) and the non-epileptic Sprague-Dawley (SD) strain of rat. GAD-positive neurons are abundant in the IC and a significant increase in the number of GAD-positive neurons occurs in the GEPR as compared to the SD in all three subdivisions. However, the most pronounced difference occurs in the ventral lateral portion of the central nucleus, where there is a selective increase in the small (200%) and medium-sized (90%) GABAergic somata (10-15 microns in diameter and 15-25 microns in diameter, respectively). As determined from Nissl preparations an increase in total numbers of neurons also occurs. Thus, a 100% increase in the number of small neurons and a 30% increase in the number of medium-sized neurons occur in the adult GEPR as compared to the SD rat. A statistically significant increase in the numbers of small neurons also occurred in the IC of the young GEPR. At 4 days of age, a 55% increase in the number of small neurons was found, and at 10 days of age this increase was 105%. The numbers of the medium and large neurons were similar in the older group of rats. These data suggest that the increase in cell number observed in the adult GEPR is not compensatory to the seizure activity, but may either be genetically programmed or be a failure of cell death. Based on other studies of genetic models of epilepsy, we propose that the additional GABAergic neurons may disinhibit excitatory projection neurons in the IC.

  4. Pharmacokinetics and cardiovascular effect of etoricoxib in the absence or presence of St. John's Wort in rats.

    PubMed

    Radwan, M A; Baky, N A A; Zaghloul, I; Aboul-Enein, H Y

    2012-07-01

    The effect of chronic administration of etoricoxib (EXB), in the absence or presence of St. John's Wort (SJW), on its pharmacokinetic parameters and blood pressure was investigated in rats.Rats were divided into 3 groups, each group received daily different oral treatment for 3 weeks. Rats' blood pressures were monitored initially, after 1 and 3 weeks of treatment, and after 1 week of discontinuing dosing of both drugs. EXB pharmacokinetic parameters in the absence or presence of SJW were calculated after 3 weeks.SJW was significantly affected EXB pharmacokinetic parameters. The steady state peak plasma concentration and terminal half-life were reduced by 32% and 91%, respectively, due to a > 3 fold increase in its apparent clearance which is a concentration and time dependent effect. EXB was significantly increased (P<0.001) Rats' blood pressure while, co-administration of EXB and SJW was not significantly affect (P>0.05) rats' blood pressure as compared to the control.Monitoring blood pressure of patients anticipated taking EXB for extended period should be advised. The co-administration of SJW with EXB should be avoided since SJW would greatly reduce EXB concentrations by inducing its metabolism.

  5. Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.

    PubMed

    Omerbašić, Damir; Smith, Ewan St J; Moroni, Mirko; Homfeld, Johanna; Eigenbrod, Ole; Bennett, Nigel C; Reznick, Jane; Faulkes, Chris G; Selbach, Matthias; Lewin, Gary R

    2016-10-11

    The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.

  6. Rapamycin attenuates aggressive behavior in a rat model of pilocarpine-induced epilepsy

    PubMed Central

    Huang, Xiaoxing; McMahon, John; Huang, Yunfei

    2012-01-01

    Psychiatric disorders are fairly common comorbidities of epilepsy in humans. Following pilocarpine-induced status epilepticus (SE), experimental animals not only developed spontaneous recurrent seizures, but also exhibited significantly elevated levels of aggressive behavior. The cellular and molecular mechanism triggering these behavioral alterations remains unclear. In the present study, we found that aggression is positively correlated with development of spontaneous seizures. Treatment with rapamycin, a potent mTOR pathway inhibitor, markedly diminished aggressive behavior. Therefore, the mTOR pathway may have significance in the underlying molecular mechanism leading to aggression associated with epilepsy. PMID:22522471

  7. Comparative analysis of the treatment of chronic antipsychotic drugs on epileptic susceptibility in genetically epilepsy-prone rats.

    PubMed

    Citraro, Rita; Leo, Antonio; Aiello, Rossana; Pugliese, Michela; Russo, Emilio; De Sarro, Giovambattista

    2015-01-01

    Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

  8. Complementation of temperature tolerance by rat Rgl-1 recessive oncogene in the absence of Saccharomyces cerevisiae Sop genes.

    PubMed

    Kim, Yu-Kyung; Kim, Yong-Soo; Chung, Hyung-Min; Baek, Kwang-Hyun

    2004-11-01

    It has been demonstrated that homozygous mutations at the L(2)gl locus in Drosophila result in the development of tumor in the presumptive adult optic centers of the larval brain and of the imaginal discs. We previously cloned an L(2)gl homologue, Rgl-1, in the rat brain. In this study, we analyzed the capability of Rgl-1 in recovering temperature tolerance in the absence of Saccharomyces cerevisiae Sop genes, yeast homologues of the Drosophila recessive oncogene Lethal (2) giant larvae. The expression of Rgl-1 revealed the recovery of temperature tolerance at 20 degrees C in the absence of Sop genes in Saccharomyces cerevisiae. This indicates that the Rgl-1 cDNA we isolated from the rat brain is highly homologous to Lgl family members and can also substitute the function of Sop proteins for temperature tolerance in Saccharomyces cerevisiae.

  9. A new trick of INPP4A: decreased expression of INPP4A in patients with temporal lobe epilepsy and pilocarpine-induced rat model.

    PubMed

    Wang, Li; Luo, Jing; Fang, Min; Jiang, Guohui; Zhang, Xiaogang; Yu, Weihua; Wang, Xuefeng

    2012-06-01

    Inositol polyphosphate phosphatase 4 A (INPP4A), a phosphoinositides phosphatase, is highly expressed in the central nervous system and plays a role in glutamate excitotoxicity and cell proliferation. Our aim was to investigate the expression of INPP4A in patients with temporal lobe epilepsy (TLE) and in a rat model of epilepsy. We assessed the expression of INPP4A in the temporal neocortex from 20 TLE patients. The result showed that INPP4A expression was significantly lower in TLE patients than in controls. To validate the results found in TLE patients, we assessed the expression of INPP4A in rat model. Rat epilepsy was induced by lithium-pilocarpine. Expression of INPP4A of rat models was assessed by immunohistochemistry, immunofluorescence, and Western blotting. INPP4A was expressed in the membrane and cytoplasm of neurons. In the hippocampus and neocortex of epileptic rats, INPP4A expression was first downregulated at the 24 h after seizures and maintained decreased levels at 72 h, 7 days, 14 days, 30 days, and 60 days, respectively. These results suggest that a decreased expression of INPP4A in the brain may be associated with TLE.

  10. Protection against hyperoxia by serum from endotoxin treated rats: absence of superoxide dismutase induction

    SciTech Connect

    Berg, J.T.; Smith, R.M.

    1988-01-01

    Endotoxin greatly reduces lung injury and pleural effusions in adult rats exposed to normobaric hyperoxia (> 98% oxygen for 60 hours). This study reports that serum from endotoxin treated donor rats protects serum recipients against hyperoxic lung injury without altering lung superoxide dismutase (SOD) activity. Rats pretreated with endotoxin alone were protected and exhibited an increase in lung SOD activity as previously reported by others. Protection by serum was not due to the transfer of residual endotoxin or SOD. These results show, that protection from oxygen toxicity can occur in rats without an increase in lung SOD and suggest that a serum factor may be involved.

  11. [Myoclonus and myoclonic epilepsies in childhood].

    PubMed

    Nieto-Barrera, M

    Myoclonic jerks occur in a number of different syndromes. There is many classifications of myoclonus. It is preferred the Fejerman classification, slightly modified that present the following five groups: 1. Myoclonus without encephalopathy and without epilepsy, which includes physiological myoclonus; 2. Encephalopathies with non epileptic myoclonus, which includes Kinsbourne syndrome and certain types of hyperekplexia which pose differential diagnosis problems with reflex myoclonic epilepsy; 3. Progressive encephalopathies with myoclonic seizures which includes typical and atypical progressive myoclonus epilepsies; 4. Epilepsies and epileptic encephalopathies with myoclonic seizures, which includes severe epilepsies which leads to mental retardation, as Otahara syndrome, West syndrome and Lennox-Gastaut syndrome, and other epilepsies which present sometimes myoclonic seizures, as Landau-Kleffner syndrome, 5. Comprises true myoclonic epilepsies, differentiating syndromes recognized as idiopathic, -benign myoclonic epilepsy of infancy, reflex form of benign myoclonic epilepsy in infancy, eyelid myoclonic with absences, perioral myoclonic with absences and juvenile myoclonic epilepsy-, cryptogenic-severe myoclonic epilepsy of infancy, myoclonic-astatic epilepsy and epilepsy with myoclonic absences-, and symptomatic as the generalized myoclonus in children with static encephalopathies. The epileptic syndromes of the last group are described. Despite this classification, apparently clear, there is still a great deal of confusion and in clinical practice, many cases are difficult to classify.

  12. The influence of manganese supplementation on seizure onset and severity, and brain monoamines in the genetically epilepsy prone rat.

    PubMed

    Critchfield, J W; Carl, G F; Keen, C L

    1993-01-01

    Human and experimental animal studies suggest a relationship between low Mn status and seizures. The genetically epilepsy prone rat (GEPR), which has low tissue Mn levels, was studied in the context of Mn supplementation. Manganese was provided at 45 micrograms/g diet (control) or 1000 micrograms/g diet (supplemented) to dams during pregnancy and lactation, then to the offspring after weaning. Offspring were tested for seizure susceptibility as young adults; tissue trace elements, brain monoamines and brain glutamine synthetase activity were measured as endpoint biochemical indices. Supplementation, although developmentally encompassing and highly effective in elevating tissue Mn levels, had no effect on seizure latency or severity. Similarly, brain monoamine concentrations and glutamine synthetase activities were resistant to Mn supplementation. Notably, the GEPR was confirmed to have low whole brain glutamine synthetase activity. These findings suggest that seizure activity in the GEPR does not stem from an increased nutritional/metabolic need for Mn.

  13. 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.

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

    PubMed

    Vadász, C; Carpi, D; Jando, G; Kandel, A; Urioste, R; Horváth, Z; Pierre, E; Vadi, D; Fleischer, A; Buzsáki, 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 a 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.

  15. [GABAergic mechanisms in generalized epilepsies: the neuroanatomical dimension].

    PubMed

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

    1997-01-01

    Generalized epileptic seizures are underlied by specific circuits where GABAergic synapses are involved at different levels. The role of these synapses depends on (i) the type of epilepsy and (ii) their localization within the central nervous system. This dual complexity can be illustrated by two examples from animal experimentation. Clinical, as well as experimental data have shown that the neural mechanisms underlying generalized non-convulsive seizures (e.g., absence-epilepsy) are distinct from those involved in convulsive generalized seizures. Pharmacological reactivity to anti-epileptic compounds is different between these two forms of seizures. Hippocampus and amygdala are key-structures in convulsive seizures whereas they are not involved in absence-epilepsy. A thalamo-cortical circuit generates the spike-and-wave discharges in absence epilepsy. Global activation of GABAergic transmission by systemic administration generally suppresses convulsive seizures whereas it aggravates absence in both humans and animals. Further investigations using a genetic model of absence seizures in the rat have suggested that this aggravation may be related to the role of post-synaptic GABA-B receptors in slow hyperpolarization, in the relay nuclei of the thalamus. By "de-inactivating" low-threshold calcium currents, activation of these receptors facilitates rhythmic activity in the thalamo-cortical circuit. In addition, regulation of transmitter release by presynaptic GABA-B receptors in the thalamus and the cortex may also contribute to the control of absence seizures. A blockade of the GABA-B receptors, either locally in the thalamus or systemically suppresses absence seizures. The critical role of the substantia nigra in the control of different forms of seizures has been demonstrated recently in the rat. This structure is one of the richest regions of the brain for GABAergic terminals, neurons and receptors. Local applications of GABA mimetics resulting in the

  16. Various modifications of the intrahippocampal kainate model of mesial temporal lobe epilepsy in rats fail to resolve the marked rat-to-mouse differences in type and frequency of spontaneous seizures in this model.

    PubMed

    Klee, Rebecca; Brandt, Claudia; Töllner, Kathrin; Löscher, Wolfgang

    2017-02-03

    Temporal lobe epilepsy (TLE) is the most common type of acquired epilepsy in adults. TLE can develop after diverse brain insults, including traumatic brain injury, infections, stroke, or prolonged status epilepticus (SE). Post-SE rodent models of TLE are widely used to understand mechanisms of epileptogenesis and develop treatments for epilepsy prevention. In this respect, the intrahippocampal kainate model of TLE in mice is of interest, because highly frequent spontaneous electrographic seizures develop in the kainate focus, allowing evaluation of both anti-seizure and anti-epileptogenic effects of novel drugs with only short EEG recording periods, which is not possible in any other model of TLE, including the intrahippocampal kainate model in rats. In the present study, we investigated whether the marked mouse-to-rat difference in occurrence and frequency of spontaneous seizures is due to a species difference or to technical variables, such as anesthesia during kainate injection, kainate dose, or location of kainate injection and EEG electrode in the hippocampus. When, as in the mouse model, anesthesia was used during kainate injection, only few rats developed epilepsy, although severity or duration of SE was not affected by isoflurane. In contrast, most rats developed epilepsy when kainate was injected without anesthesia. However, frequent electrographic seizures as observed in mice did not occur in rats, irrespective of location of kainate injection (CA1, CA3) or EEG recording electrode (CA1, CA3, dentate gyrus) or dose of kainate injected. These data indicate marked phenotypic differences between mice and rats in this model. Further studies should explore the mechanisms underlying this species difference.

  17. Lovastatin decreases the synthesis of inflammatory mediators during epileptogenesis in the hippocampus of rats submitted to pilocarpine-induced epilepsy.

    PubMed

    Gouveia, T L F; Scorza, F A; Iha, H A; Frangiotti, M I B; Perosa, S R; Cavalheiro, E A; Silva, J A; Feliciano, R S; de Almeida, A C; Naffah-Mazzacoratti, M G

    2014-07-01

    Statins may act on inflammatory responses, decreasing oxidative stress and also reducing brain inflammation in several brain disorders. Epileptogenesis is a process in which a healthy brain becomes abnormal and predisposed to generating spontaneous seizures. We previously reported that lovastatin could prevent neuroinflammation in pilocarpine-induced status epilepticus (SE). In this context, this study investigated the long-lasting effects of lovastatin on mRNA expression of proinflammatory cytokines (interleukin-1β, tumor necrosis factor α, interleukin-6) and the antiinflammatory cytokine IL-10 in the hippocampus during epileptogenesis by immunohistochemistry and real time polymerase chain reaction (RT-PCR) during the latent and chronic phases in the epilepsy model induced by pilocarpine in rats. For these purposes, four groups of rats were employed: saline (CONTROL), lovastatin (LOVA), pilocarpine (PILO), and pilocarpine plus lovastatin (PILO+LOVA). After pilocarpine injection (350mg/kg, i.p.), the rats were treated with 20mg/kg of lovastatin via an esophagic probe 2h after SE onset. All surviving rats were continuously treated during 15days, twice/day. The pilocarpine plus lovastatin group showed a significant decrease in the levels of IL-1β, TNF-α, and IL-6 during the latent phase and a decreased expression of IL-1β and TNF-α in the chronic phase when compared with the PILO group. Moreover, lovastatin treatment also induced an increased expression of the antiinflammatory cytokine, IL-10, in the PILO+LOVA group when compared with the PILO group in the chronic phase. Thus, our data suggest that lovastin may reduce excitotoxicity during epileptogenesis induced by pilocarpine by increasing the synthesis of IL-10 and decreasing proinflammatory cytokines in the hippocampus.

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

    PubMed Central

    Althaus, A. L.; Sagher, O.; Parent, J. M.

    2014-01-01

    Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2–4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. PMID:25429123

  19. Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

    PubMed Central

    Do Val-da Silva, Raquel A.; Peixoto-Santos, Jose E.; Kandratavicius, Ludmyla; De Ross, Jana B.; Esteves, Ingrid; De Martinis, Bruno S.; Alves, Marcela N. R.; Scandiuzzi, Renata C.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Crippa, Jose A.; Leite, Joao P.

    2017-01-01

    The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders. PMID:28367124

  20. 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.

  1. The effect of experimental epilepsy induced by injection of tetanus toxin into the amygdala of the rat on eating behaviour and response to novelty.

    PubMed

    Mellanby, J; Oliva, M; Peniket, A; Nicholls, B

    1999-04-01

    A minute dose of tetanus toxin injected into the amygdala of rats produced an apparently reversible epileptiform syndrome similar to that previously described after injection of the toxin into the hippocampus. During the active epilepsy the toxin-injected rats occasionally exhibited 'paroxysmal eating' and also sometimes ran round in circles attempting to bite their own tails. When presented with a novel but palatable food (chocolate buttons or harvest crunch) the toxin-injected rats showed less neophobia than their controls--they ate sooner and ate more. This was found both during the active epilepsy and several weeks later when they had recovered. A similar effect of amygdala injections was found in a second experiment, in which the effect was compared with that of toxin injection in the hippocampus. These rats were tested also on the playground maze on their approach response to a neutral novel object (in a familiar environment in the context of seven familiar objects). The amygdala rats did not show any increase in their novelty response; thus their reduction in neophobia was specific to an appetitive behaviour. In contrast, the hippocampally-injected rats did not exhibit a novelty response in the playground maze, but showed normal neophobia to a new food.

  2. 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.

  3. Inhibition of adenosine metabolism induces changes in post-ictal depression, respiration, and mortality in genetically epilepsy prone rats.

    PubMed

    Kommajosyula, Srinivasa P; Randall, Marcus E; Faingold, Carl L

    2016-01-01

    A major cause of mortality in epilepsy patients is sudden unexpected death in epilepsy (SUDEP). Post-ictal respiratory dysfunction following generalized convulsive seizures is most commonly observed in witnessed cases of human SUDEP. DBA mouse models of SUDEP are induced by audiogenic seizures (AGSz) and show high incidences of seizure-induced death due to respiratory depression. The relatively low incidence of human SUDEP suggests that it may be useful to examine seizure-associated death in an AGSz model that rarely exhibits sudden death, such as genetically epilepsy-prone rats (GEPR-9s). Adenosine is released extensively during seizures and depresses respiration, which may contribute to seizure-induced death. The present study examined the effects of inhibiting adenosine metabolism on the durations of post-ictal depression (PID) and respiratory distress (RD), changes in blood oxygen saturation (% SpO2), and the incidence of post-seizure mortality in GEPR-9s. Systemic administration of adenosine metabolism inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 30 mg/kg) with 5-Iodotubericidin (5-ITU, 3mg/kg) in GEPR-9s resulted in significant changes in the duration of AGSz-induced PID as compared to vehicle in both genders. These agents also significantly increased the duration of post-seizure RD and significantly decreased the mean% SpO2 after AGSz, as compared to vehicle but only in females. Subsequently, we observed that the incidences of death in both genders 12-48 h post-seizure were significantly greater in drug vs. vehicle treatment. The incidence of death in females was also significantly higher than in males, which is consistent with the elevated seizure sensitivity of female GEPR-9s developmentally. These results support a potentially important role of elevated adenosine levels following generalized seizures in the increased incidence of death in GEPR-9s induced by adenosine metabolism inhibitors. These findings may also be relevant to human SUDEP, in

  4. 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

  5. Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract.

    PubMed

    Krishnakumar, Amee; Abraham, Pretty Mary; Paul, Jes; Paulose, C S

    2009-09-15

    Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT(2C) receptors. 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs. In the present study, we investigated the changes in the 5-HT(2C) receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (p<0.001), 5-HT(2C) gene expression (p<0.001) and 5-HT(2C) receptor binding (p<0.001) with an increased affinity (p<0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (p<0.01), 5-HT(2C) receptor binding (p<0.001) and gene expression (p<0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT(2C) receptor in epileptic rats. This has clinical significance in the management of epilepsy.

  6. Epilepsy but not mobile phone frequency (900 MHz) induces apoptosis and calcium entry in hippocampus of epileptic rat: involvement of TRPV1 channels.

    PubMed

    Nazıroğlu, Mustafa; Özkan, Fatma Feyza; Hapil, Seher Rabia; Ghazizadeh, Vahid; Çiğ, Bilal

    2015-02-01

    Electromagnetic radiation (EMR) and epilepsy are reported to mediate the regulation of apoptosis and oxidative stress through Ca(2+) influx. Results of recent reports indicated that EMR can increase temperature and oxidative stress of body cells, and TRPV1 channel is activated by noxious heat, oxidative stress, and capsaicin (CAP). We investigated the effects of mobile phone (900 MHz) EMR exposure on Ca(2+) influx, apoptosis, oxidative stress, and TRPV1 channel activations in the hippocampus of pentylenetetrazol (PTZ)-induced epileptic rats. Freshly isolated hippocampal neurons of twenty-one rats were used in study within three groups namely control, PTZ, and PTZ + EMR. The neurons in the three groups were stimulated by CAP. Epilepsy was induced by PTZ administration. The neurons in PTZ + EMR group were exposed to the 900 MHz EMR for 1 h. The apoptosis, mitochondrial membrane depolarization, intracellular reactive oxygen species (ROS), and caspase-3 and caspase-9 values were higher in PTZ and PTZ + EMR groups than in control. However, EMR did not add additional increase effects on the values in the hippocampal neurons. Intracellular-free Ca(2+) concentrations in fura-2 analyses were also higher in PTZ + CAP group than in control although their concentrations were decreased by TRPV1 channel blocker, capsazepine. However, there were no statistical changes on the Ca(2+) concentrations between epilepsy and EMR groups. In conclusion, apoptosis, mitochondrial, ROS, and Ca(2+) influx via TRPV1 channel were increased in the hippocampal neurons by epilepsy induction although the mobile phone did not change the values. The results indicated that TRPV1 channels in hippocampus may possibly be a novel target for effective target of epilepsy.

  7. 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.

  8. Microsensors and wireless system for monitoring epilepsy

    NASA Astrophysics Data System (ADS)

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

    2003-07-01

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

  9. 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.

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

    PubMed

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

    2002-08-01

    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 microM 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 alpha(2) homomeric GlyRs in neonatal rats and alpha(1)/beta 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 microM gabazine blocked spontaneous or evoked inhibitory synaptic current, while the addition of 1 microM 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.

  11. Epilepsy Foundation

    MedlinePlus

    ... the Facts Take Charge of the Storm Rick Harrison of 'Pawn Stars' Partners with Epilepsy Foundation to ... the Facts Take Charge of the Storm Rick Harrison of 'Pawn Stars' Partners with Epilepsy Foundation to ...

  12. 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

  13. Axonal plasticity of age-defined dentate granule cells in a rat model of mesial temporal lobe epilepsy.

    PubMed

    Althaus, A L; Zhang, H; Parent, J M

    2016-02-01

    Dentate granule cell (DGC) mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (mTLE) is thought to underlie the creation of aberrant circuitry which promotes the generation or spread of spontaneous seizure activity. Understanding the extent to which populations of DGCs participate in this circuitry could help determine how it develops and potentially identify therapeutic targets for regulating aberrant network activity. In this study, we investigated how DGC birthdate influences participation in MFS and other aspects of axonal plasticity using the rat pilocarpine-induced status epilepticus (SE) model of mTLE. We injected a retrovirus (RV) carrying a synaptophysin-yellow fluorescent protein (syp-YFP) fusion construct to birthdate DGCs and brightly label their axon terminals, and compared DGCs born during the neonatal period with those generated in adulthood. We found that both neonatal and adult-born DGC populations participate, to a similar extent, in SE-induced MFS within the dentate gyrus inner molecular layer (IML). SE did not alter hilar MF bouton density compared to sham-treated controls, but adult-born DGC bouton density was greater in the IML than in the hilus after SE. Interestingly, we also observed MF axonal reorganization in area CA2 in epileptic rats, and these changes arose from DGCs generated both neonatally and in adulthood. These data indicate that both neonatal and adult-generated DGCs contribute to axonal reorganization in the rat pilocarpine mTLE model, and indicate a more complex relationship between DGC age and participation in seizure-related plasticity than was previously thought.

  14. AXONAL PLASTICITY OF AGE-DEFINED DENTATE GRANULE CELLS IN A RAT MODEL OF MESIAL TEMPORAL LOBE EPILEPSY

    PubMed Central

    Althaus, AL; Zhang, H; Parent, JM

    2016-01-01

    Dentate granule cell (DGC) mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (mTLE) is thought to underlie the creation of aberrant circuitry which promotes the generation or spread of spontaneous seizure activity. Understanding the extent to which populations of DGCs participate in this circuitry could help determine how it develops and potentially identify therapeutic targets for regulating aberrant network activity. In this study, we investigated how DGC birthdate influences participation in MFS and other aspects of axonal plasticity using the rat pilocarpine-induced status epilepticus (SE) model of mTLE. We injected a retrovirus (RV) carrying a synaptophysin-yellow fluorescent protein (syp-YFP) fusion construct to birthdate DGCs and brightly label their axon terminals, and compared DGCs born during the neonatal period with those generated in adulthood. We found that both neonatal and adult-born DGC populations participate, to a similar extent, in SE-induced MFS within the dentate gyrus inner molecular layer (IML). SE did not alter hilar MF bouton density compared to sham-treated controls, but adult-born DGC bouton density was greater in the IML than in the hilus after SE. Interestingly, we also observed MF axonal reorganization in area CA2 in epileptic rats, and these changes arose from DGCs generated both neonatally and in adulthood. These data indicate that both neonatal and adult-generated DGCs contribute to axonal reorganization in the rat pilocarpine mTLE model, and indicate a more complex relationship between DGC age and participation in seizure-related plasticity than was previously thought. PMID:26644085

  15. 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.

  16. Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation.

    PubMed

    Urbizu, Aintzane; Cuenca-León, Ester; Raspall-Chaure, Miquel; Gratacòs, Margarida; Conill, Joan; Redecillas, Susana; Roig-Quilis, Manuel; Macaya, Alfons

    2010-08-15

    We report two monochorionic twins that progressively developed, between ages 5 and 10, a combination of episodic neurological disorders including paroxysmal exercise-induced dyskinesia, migraine without or with aura, absence seizures and writer's cramp. CSF/serum glucose ratio was moderately decreased in both patients. Mutational analysis of SLC2A1 gene identified a de novo heterozygous missense mutation in exon 4. This novel mutation has been previously showed to disrupt glucose transport in vitro. Both patients showed immediate and near-complete response to ketogenic diet. This clinical observation suggests that a high index of suspicion for GLUT1 deficiency syndrome is warranted in evaluating patients with multiple neurological paroxysmal events.

  17. Epigenetics and epilepsy.

    PubMed

    Roopra, Avtar; Dingledine, Raymond; Hsieh, Jenny

    2012-12-01

    Seizures can give rise to enduring changes that reflect alterations in gene-expression patterns, intracellular and intercellular signaling, and ultimately network alterations that are a hallmark of epilepsy. A growing body of literature suggests that long-term changes in gene transcription associated with epilepsy are mediated via modulation of chromatin structure. One transcription factor in particular, repressor element 1-silencing transcription factor (REST), has received a lot of attention due to the possibility that it may control fundamental transcription patterns that drive circuit excitability, seizures, and epilepsy. REST represses a suite of genes in the nervous system by utilizing nuclear protein complexes that were originally identified as mediators of epigenetic inheritance. Epigenetics has traditionally referred to mechanisms that allow a heritable change in gene expression in the absence of DNA mutation. However a more contemporaneous definition acknowledges that many of the mechanisms used to perpetuate epigenetic traits in dividing cells are utilized by neurons to control activity-dependent gene expression. This review surveys what is currently understood about the role of epigenetic mechanisms in epilepsy. We discuss how REST controls gene expression to affect circuit excitability and neurogenesis in epilepsy. We also discuss how the repressor methyl-CpG-binding protein 2 (MeCP2) and activator cyclic AMP response element binding protein (CREB) regulate neuronal activity and are themselves controlled by activity. Finally we highlight possible future directions in the field of epigenetics and epilepsy.

  18. Hypertension induced by high salt intake in absence of volume retention in reduced renal mass rats.

    PubMed

    Cowley, A W; Skelton, M M; Papanek, P E; Greene, A S

    1994-11-01

    Reduction of renal mass (RRM) combined with a high-salt diet results in volume retention, a rise of cardiac output, and hypertension. The present studies were designed to determine whether prevention of volume retention would alter the rise of mean arterial pressure (MAP) in RRM rats given high salt. Rats were studied in a modified metabolic cage to permit continuous determination of total body weight (TBW). In group 1, NaCl was increased from 1 to 14.5 meq/day and delivered isotonically. In group 2, NaCl was increased while TBW was servo-controlled to a constant level. Group 3 was also servo-controlled, but rats received an intravenous infusion of an arginine vasopressin V1 antagonist throughout the study. MAP in group 1 rose 24 mmHg by day 4 of high salt with a parallel increase of TBW of 26 g. In group 2, MAP rose 48 mmHg by day 4 of high salt, while TBW was controlled to within 0.6% of control body weight. With inhibition of vasopressin V1 receptors (group 3), MAP rose 39 mmHg. Nearly equivalent amounts of NaCl were retained in all groups, which was associated with no change of plasma Na in group 1 but an increase of nearly 7 meq/ml in groups 2 and 3. Hematocrit fell nearly 9% in groups 2 and 3 compared with a 4% reduction in group 1. The results suggest that under conditions where net retention cannot occur, high salt intake increases MAP by an osmotically driven fluid transfer from cells, which results in an even greater expansion of blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. 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.

  20. Hypotonic shocks activate rat TRPV4 in Yeast in the Absence of Polyunsaturated Fatty Acids

    PubMed Central

    Loukin, Stephen H.; Su, Zhenwei; Kung, Ching

    2010-01-01

    Transient-receptor-potential channels (TRPs) underlie the sensing of chemicals, heat, and mechanical force. We expressed the rat TRPV1 and TRPV4 subtypes in yeast and monitored their activities in vivo as Ca2+ rise using transgenic aequorin. Heat and capsaicin activate TRPV1 but not TRPV4 in yeast. Hypotonic shocks activate TRPV4 but not TRPV1. Osmotic swelling is modeled to activate enzyme(s), producing polyunsaturated fatty acids (PUFAs) to open TRPV4 in mammalian cells. This model relegates mechanosensitivity to the enzyme and not the channel. Yeast has only a single Δ9 fatty-acid monodesaturase and cannot make PUFAs suggesting an alternative mechanism for TRPV4 activation. We discuss possible explanations of this difference. PMID:19174160

  1. Increased excitatory synaptic input to granule cells from hilar and CA3 regions in a rat model of temporal lobe epilepsy

    PubMed Central

    Zhang, Wei; Huguenard, John R.; Buckmaster, Paul S.

    2012-01-01

    One potential mechanism of temporal lobe epilepsy is recurrent excitation of dentate granule cells through aberrant sprouting of their axons (mossy fibers), which is found in many patients and animal models. However, correlations between the extent of mossy fiber sprouting and seizure frequency are weak. Additional potential sources of granule cell recurrent excitation that would not have been detected by markers of mossy fiber sprouting in previous studies include surviving mossy cells and proximal CA3 pyramidal cells. To test those possibilities in hippocampal slices from epileptic pilocarpine-treated rats, laser scanning glutamate uncaging was used to randomly and focally activate neurons in the granule cell layer, hilus, and proximal CA3 pyramidal cell layer while measuring evoked excitatory postsynaptic currents (EPSCs) in normotopic granule cells. Consistent with mossy fiber sprouting, a higher proportion of glutamate-uncaging spots in the granule cell layer evoked EPSCs in epileptic rats compared to controls. In addition, stimulation spots in the hilus and proximal CA3 pyramidal cell layer were more likely to evoke EPSCs in epileptic rats, despite significant neuron loss in those regions. Furthermore, synaptic strength of recurrent excitatory inputs to granule cells from CA3 pyramidal cells and other granule cells was increased in epileptic rats. These findings reveal substantial levels of excessive, recurrent, excitatory synaptic input to granule cells from neurons in the hilus and proximal CA3 field. The aberrant development of these additional positive-feedback circuits might contribute to epileptogenesis in temporal lobe epilepsy. PMID:22279204

  2. 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 Central

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

    2015-01-01

    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 21 days after the onset of MSO infusion. Sucrose preference, a measure of anhedonia, was assessed after 21 days. 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

  3. 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.

  4. 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

  5. Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

    PubMed

    Ghazizadeh, Vahid; Nazıroğlu, Mustafa

    2014-09-01

    Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

  6. Peritoneal dialysis fluid-induced angiogenesis in rat mesentery is increased by lactate in the presence or absence of glucose.

    PubMed

    Albrektsson, Ann; Bazargani, Farhan; Wieslander, Anders; Braide, Magnus

    2006-01-01

    Angiogenesis may be an important mechanism behind the functional deterioration of the peritoneum leading to ultrafiltration failure in peritoneal dialysis. The present study was designed to compare the angiogenic properties of lactate-, bicarbonate-, and pyruvate-buffered fluids, evaluated separately with and without glucose. Five different fluids (lactate and bicarbonate with and without 2.5% glucose and pyruvate without glucose) were studied for 5 weeks of twice-daily injections in rats. The respective buffers (40 mmol/l) were adjusted to pH 7.2, and sodium, chloride, calcium, and magnesium were present at standard concentrations. The mesenteric window model, based on observation of the translucent peritoneal sections of the small intestine mesentery, was used for immunohistochemical imaging of microvessels (RECA-1 antigen) and macrophages (ED1 and ED2 antigens). All fluids induced angiogenesis as compared with untreated controls. The lactate-buffered fluids induced larger vascularized zones than did their bicarbonate- and pyruvate-buffered counterparts. Angiogenesis was accompanied by a local recruitment of ED1 macrophages from blood. Addition of glucose to the lactate- and bicarbonate-buffered fluids did not seem to alter their pro-angiogenic properties. In conclusion, intraperitoneal exposure to lactate buffer, compared with bicarbonate, stimulates angiogenesis in the presence or absence of glucose.

  7. Protein expression of small conductance calcium-activated potassium channels is altered in inferior colliculus neurons of the genetically epilepsy-prone rat

    PubMed Central

    N’Gouemo, Prosper; Yasuda, Robert P.; Faingold, Carl L.

    2009-01-01

    The genetically epilepsy-prone rat (GEPR) exhibits inherited predisposition to sound stimuli-induced generalized tonic-clonic seizures (audiogenic reflex seizures) and is a valid model to study the physiopathology of epilepsy. In this model, the inferior colliculus (IC) exhibits enhanced neuronal firing that is critical in the initiation of reflex audiogenic seizures. The mechanisms underlying IC neuronal hyperexcitability that leads to seizure susceptibility are not as yet fully understood. The present report shows that the levels of protein expression of SK1 and SK3 subtypes of the small conductance Ca2+-activated K+ channels were significantly decreased, while SK2 channel proteins were increased in IC neurons of seizure-naive GEPR-3s (SN-GEPR-3), as compared to control Sprague-Dawley rats. No significant change was found in the expression of BK channel proteins in IC neurons of SN-GEPR-3s. Single episode of reflex audiogenic seizures in the GEPR-3s did not significantly alter the protein expression of SK1-3 and BK channels in IC neurons compared to SN-GEPR-3s. Thus, downregulation of SK1 and SK3 channels and upregulation of SK2 channels provide direct evidence that these Ca2+-activated K+ channels play important roles in IC neuronal hyperexcitability that leads to inherited seizure susceptibility in the GEPR. PMID:19254702

  8. Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy

    PubMed Central

    Faria, Leonardo C.

    2010-01-01

    Partially isolated “undercut” neocortex with intact pial circulation is a well-established model of posttraumatic epileptogenesis. Results of previous experiments showed a decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal (Pyr) neurons of undercuts. We further examined possible functional abnormalities in GABAergic inhibition in rat epileptogenic neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. Compared with controls, IPSCs in Pyr neurons of injured slices showed increased threshold and decreased peak amplitude at threshold, decreased input/output slopes, increased failure rates, and a shift from paired pulse depression toward paired pulse facilitation (increased paired pulse ratio or PPR). Increasing [Ca2+]o from 2 to 4 mM partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto FS cells also had an increased PPR and failures. Blockade of GABAB receptors did not affect the paired results. These findings suggest that there are functional alterations in GABAergic presynaptic terminals onto both Pyr and FS cells in this model of posttraumatic epileptogenesis. PMID:20484536

  9. Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat

    PubMed Central

    Leroy, Claire; Pierre, Karin; Simpson, Ian A.; Pellerin, Luc; Vannucci, Susan J.; Nehlig, Astrid

    2013-01-01

    The lithium-pilocarpine model mimics most features of human temporal lobe epilepsy. Following our prior studies of cerebral metabolic changes, here we explored the expression of transporters for glucose (GLUT1 and GLUT3) and monocarboxylates (MCT1 and MCT2) during and after status epilepticus (SE) induced by lithium-pilocarpine in PN10, PN21, and adult rats. In situ hybridization was used to study the expression of transporter mRNAs during the acute phase (1, 4, 12 and 24 h of SE), the latent phase, and the early and late chronic phases. During SE, GLUT1 expression was increased throughout the brain between 1 and 12 h of SE, more strongly in adult rats; GLUT3 increased only transiently, at 1 and 4 h of SE and mainly in PN10 rats; MCT1 was increased at all ages but 5-10-fold more in adult than immature rats; MCT2 expression increased mainly in adult rats. At all ages, MCT1 and MCT2 up-regulation was limited to the circuit of seizures while GLUT1 and GLUT3 changes were more widespread. During the latent and chronic phases, the expression of nutrient transporters was normal in PN10 rats. In PN21 rats, GLUT1 was up-regulated in all brain regions. In contrast, in adult rats GLUT1 expression was down-regulated in the piriform cortex, hilus and CA1 as a result of extensive neuronal death. The changes in nutrient transporter expression reported here further support previous findings in other experimental models demonstrating rapid transcriptional responses to marked changes in cerebral energetic/glucose demand. PMID:21624469

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

    PubMed

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

    2014-10-15

    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.

  11. 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

  12. About Epilepsy

    MedlinePlus

    ... diagnosed? How is epilepsy treated? What is an electroencephalography (EEG)? What is a Positron Emission Tomography (PET) ... Go back to the top What is an electroencephalography (EEG)? An electroencephalogram (EEG) is a test to ...

  13. About Epilepsy

    MedlinePlus

    ... EEG Telemetry? What is Magnetoencephalography (MEG)? What is Magnetic Resonance Imaging (MRI)? About Pre-surgical Evaluation for Epilepsy. What ... In most cases, an EEG (electroencephalogram) and MRI (magnetic resonance imaging) test will be performed as well. You will ...

  14. Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model.

    PubMed

    Luo, Jing; Xu, Yali; Zhu, Qiong; Zhao, Fenghua; Zhang, Ying; Peng, Xi; Wang, Wei; Wang, Xuefeng

    2011-11-01

    Mical-1 is a novel F-actin-disassembly factor that is critical in actin reorganization. It provides a molecular conduit through which actin reorganizes-a hallmark of cell morphological changes, including axon navigation. However, whether Mical-1 is involved in the epileptogenesis remains unknown. Here, we investigate Mical-1 expression pattern in patients with intractable temporal lobe epilepsy (TLE) and pilocarpine-induced rat model. We used double-labeled immunoflurescence, immunohistochemistry, and Western blotting to assess the location and expression of Mical-1 in temporal neocortex of patients with intractable TLE, and the expression pattern of Mical-1 at different time point in the hippocampus and temporal lobe cortex of the pilocarpine-induced rat model. Double-labeled immunofluorescence showed that Mical-1 was coexpressed with neuron-specific enolase (NSE) in the cytoplasm of neurons in temporal neocortex of patients with TLE and hippocampus of rat model. Faint and scattered immunoreactivity for Mical-1 in the neuron of temporal neocortex in TLE group, but strong immunoreactivity for Mical-1 was shown in control subjects. To quantitatively evaluate the Mical-1 immunoreactivity, we measured the mean optical density (OD) of Mical-1. In the hippocampus of pilocarpine-induced rat model, the OD values transient increased at 6 h after seizure then decreased from 1 day to 14 days, and returned to a subnormal level at 60 days. The lowest level of Mical-1 expression occurred at 14 days after seizure in the hippocampus. In the temporal lobe cortex of rat model, the OD values decreased at all time point after kindling compared to the normal group. Furthermore, our Western blot analysis confirmed these expression patterns of Mical-1 from latent stage to chronic stage. Our results indicate that in patients with TLE and pilocarpine-induced rat model, the expression of Mical-1 were followed a downtrend from the latent stage to chronic stage after seizure evoke. Thus, as

  15. Hippocampal-Dependent Spatial Memory in the Water Maze is Preserved in an Experimental Model of Temporal Lobe Epilepsy in Rats

    PubMed Central

    Inostroza, Marion; Cid, Elena; Brotons-Mas, Jorge; Gal, Beatriz; Aivar, Paloma; Uzcategui, Yoryani G.

    2011-01-01

    Cognitive impairment is a major concern in temporal lobe epilepsy (TLE). While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA) from two different rat strains (Wistar and Sprague-Dawley) using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se. PMID:21829459

  16. The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes.

    PubMed

    Fabene, P F; Correia, L; Carvalho, R A; Cavalheiro, E A; Bentivoglio, M

    2001-01-01

    At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase(67)-immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced. These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.

  17. Modulation of miR-146a/complement factor H-mediated inflammatory responses in a rat model of temporal lobe epilepsy

    PubMed Central

    He, Fang; Liu, Bei; Meng, Qiang; Sun, Yang; Wang, Weiwen; Wang, Chao

    2016-01-01

    Increasing evidence supports the involvement of inflammatory and immune processes in temporal lobe epilepsy (TLE). miRNAs represent small regulatory RNA molecules that have been shown to act as negative regulators of gene expression controlling different biological processes, including immune system homoeostasis and function. We investigated the expression and cellular distribution of miRNA-146a (miR-146a) in a rat model of TLE. Prominent up-regulation of miR-146a activation was evident in 1 week after status epilepticus (SE) and persisted in the chronic phase. The predicted miR-146a's target complement factor H (CFH) mRNA and protein expression was also down-regulated in TLE rat model. Furthermore, transfection of miR-146a mimics in neuronal and glial cells down-regulated CFH mRNA and protein levels respectively. Luciferase reporter assays demonstrated that miR-146a down-regulated CFH mRNA expression via 3′-UTR pairing. Down-regulating miR-146a by intracerebroventricular injection of antagomir-146a enhanced the hippocampal expression of CFH in TLE model and decreased seizure susceptibility. These findings suggest that immunopathological deficits associated with TLE can in part be explained by a generalized miR-146a-mediated down-regulation of CFH that may contribute to epileptogenesis in a rat model of TLE. PMID:27852797

  18. 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.

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

    PubMed

    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.

  20. Acupuncture for Refractory Epilepsy: Role of Thalamus

    PubMed Central

    Chen, Shuping; Wang, Shubin; Rong, Peijing; Liu, Junling; Zhang, Hongqi; Zhang, Jianliang

    2014-01-01

    Neurostimulation procedures like vagus nerve stimulation (VNS) and deep brain stimulation have been used to treat refractory epilepsy and other neurological disorders. While holding promise, they are invasive interventions with serious complications and adverse effects. Moreover, their efficacies are modest with less seizure free. Acupuncture is a simple, safe, and effective traditional healing modality for a wide range of diseases including pain and epilepsy. Thalamus takes critical role in sensory transmission and is highly involved in epilepsy genesis particularly the absence epilepsy. Considering thalamus serves as a convergent structure for both acupuncture and VNS and the thalamic neuronal activities can be modulated by acupuncture, we propose that acupuncture could be a promising therapy or at least a screening tool to select suitable candidates for those invasive modalities in the management of refractory epilepsy. PMID:25548594

  1. Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P.

    PubMed

    Smith, Ewan St John; Blass, Gregory R C; Lewin, Gary R; Park, Thomas J

    2010-05-24

    Recent research has proposed a pathway in which sensory neurons expressing the capsaicin activated ion channel TRPV1 are required for histamine-induced itch and subsequent scratching behavior. We examined histamine-induced itch in the African naked mole-rat (Heterocephalus glaber) and found that although naked mole-rats display innate scratching behavior, histamine was unable to evoke increased scratching as is observed in most mouse strains. Using calcium imaging, we examined the histamine sensitivity of naked mole-rat dorsal root ganglia (DRG) neurons and identified a population of small diameter neurons activated by histamine, the majority of which are also capsaicin-sensitive. This suggested that naked mole-rat sensory neurons are activated by histamine, but that spinal dorsal horn processing of sensory information is not the same as in other rodents. We have previously shown that naked mole-rats naturally lack substance P (SP) in cutaneous C-fibers, but that the neurokinin-1 receptor is expressed in the superficial spinal cord. This led us to investigate if SP deficiency plays a role in the lack of histamine-induced scratching in this species. After intrathecal administration of SP into the spinal cord we observed robust scratching behavior in response to histamine injection. Our data therefore support a model in which TRPV1-expressing sensory neurons are important for histamine-induced itch. In addition, we demonstrate a requirement for active, SP-induced post-synaptic drive to enable histamine sensitive afferents to drive itch-related behavior in the naked mole-rat. These results illustrate that it is altered dorsal horn connectivity of nociceptors that underlies the lack of itch and pain-related behavior in the naked mole-rat.

  2. American Epilepsy Society

    MedlinePlus

    ... Epilepsy Society CLINICAL RESOURCES FAQs GUIDELINES IOM EPILEPSY MEDICAL MARIJUANA SUDEP SURGERY DEVICES GENETICS TREATMENTS Drug Alerts and ... RESOURCES Navigation CLINICAL RESOURCES FAQs GUIDELINES IOM EPILEPSY MEDICAL MARIJUANA SUDEP SURGERY DEVICES GENETICS TREATMENTS Drug Alerts and ...

  3. A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.

    PubMed

    Sun, Hong-Liu; Deng, Da-Ping; Pan, Xiao-Hong; Wang, Chao-Yun; Zhang, Xiu-Li; Chen, Xiang-Ming; Wang, Chun-Hua; Liu, Yu-Xia; Li, Shu-Cui; Bai, Xian-Yong; Zhu, Wei

    2016-03-02

    The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague–Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.

  4. Intracranial pressure changes following traumatic brain injury in rats: lack of significant change in the absence of mass lesions or hypoxia.

    PubMed

    Gabrielian, Levon; Willshire, Luke W; Helps, Stephen C; van den Heuvel, Corinna; Mathias, Jane; Vink, Robert

    2011-10-01

    Traumatic brain injury (TBI) often causes raised intracranial pressure (ICP), with >50% of all TBI- related deaths being associated with this increase in ICP. To date, there is no effective pharmacological treatment for TBI, partly because widely used animal models of TBI may not replicate many of the pathophysiological responses observed in humans, and particularly the ICP response. Generally, rodents are the animal of choice in neurotrauma research, and edema formation has been demonstrated in rat models; however, few studies in rats have specifically explored the effects of TBI on ICP. The aim of the current study was to investigate the ICP response of rats in two different, focal and diffuse, injury models of TBI. Adult male Sprague-Dawley rats were subjected to brain trauma by either lateral fluid percussion or impact-acceleration induced injury, in the presence or absence of secondary hypoxia. ICP, mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were monitored for 4 h after TBI. TBI alone or coupled with hypoxia did not result in any significant increase of ICP in rats unless there was an intracranial hemorrhage. At all other times, changes in CPP were the result of changes in MABP and not ICP. Our results suggest that rats may be able to compensate for the intracranial expansion associated with cerebral edema after TBI, and that they only develop a consistent post-traumatic increase in ICP in the presence of a mass lesion. Therefore, they are an inappropriate model for the investigation of ICP changes after TBI, and for the development of therapies targeting ICP.

  5. Alterations of hippocampal GAbaergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy.

    PubMed

    André, V; Marescaux, C; Nehlig, A; Fritschy, J M

    2001-01-01

    Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CA1, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. In particular, the reorganization of GABAergic axons in the dentate gyrus might

  6. 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

  7. Increased responsiveness and failure of habituation in neurons of the external nucleus of inferior colliculus associated with audiogenic seizures of the genetically epilepsy-prone rat.

    PubMed

    Chakravarty, D N; Faingold, C L

    1996-10-01

    Initiation of audiogenic seizures (AGS) emanates from the inferior colliculus (IC) to other IC subnuclei in the genetically epilepsy-prone rat (GEPR). The external nucleus of IC (ICx) is a suggested site of convergence of the auditory output onto the sensorimotor integration network components for AGS in the brainstem. Neuronal firing was recorded from the ICx of the awake, freely moving GEPR and normal Sprague-Dawley rats using microwire electrodes in the present study. Auditory stimuli consisted of 12-kHz tones (100 ms, 5-ms rise-fall at rates of 1/4s, 1/2s, and 1/s). AGS incidence in the GEPR is highest at 12 kHz. In the GEPR, ICx neuronal responses to acoustic stimuli were significantly greater than those seen in normal rats. This increased ICx firing was observed at relatively high acoustic intensities (> 80 dB SPL), which are near the threshold for AGS induction. Repetition-induced response attenuation (habituation) is commonly observed in ICx neurons, which appears to be overcome in the GEPR during AGS initiation. Tonic, acoustically evoked ICx neuronal firing was observed just prior to wild running. ICx firing was suppressed during the tonic and postictal phases of AGS. Recovery of ICx responses occurred when the animal regained postural control. Abnormal, intense output has previously been observed in the GEPR IC central nucleus (ICc) neurons. The neuronal firing pattern changes observed in the ICx in the present study may result from this intense ICc output. Diminished efficacy of GABA, which has been observed in several regions of the GEPR brain, including the IC, in a number of previous studies, may be involved in the exaggerated ICx responses to acoustic stimuli in the GEPR. Participation of the ICx in the AGS neuronal network may be subserved by this acoustic hyperresponsiveness.

  8. [Clinical guidelines for epilepsy].

    PubMed

    Tsuji, Sadatoshi

    2014-05-01

    Many international guidelines for epilepsy from the countries in Europe, USA and Asia have been published since the introduction of evidence-based medicine. In Japan, the clinical guidelines for epilepsy management were published by the Japanese Society of Neurology (JSN) in 2002 and 2010. The clinical guideline for epilepsy 2010 primarily targets general practitioners treating epilepsy patients. The Japan Epilepsy Society has been publishing 16 guidelines for several topics since 2005. The clinical guideline for epilepsy 2010 recommends that carbamazepine can be regarded for new onset partial epilepsy and sodium valproate is for new onset generalized epilepsy as anti-epileptic drug (AED) monotherapy. The new AEDs received approval by the Ministry of Health, Labour and Welfare, Japan, mainly in the add-on treatment of adults with partial epilepsy. The clinical guideline for epilepsy 2010 will contribute to improvement in the management of epilepsy in Japan.

  9. Retrograde abolition of conditional fear after excitotoxic lesions in the basolateral amygdala of rats: absence of a temporal gradient.

    PubMed

    Maren, S; Aharonov, G; Fanselow, M S

    1996-08-01

    The role of the basolateral amygdala (LA) in the acquisition and expression of Pavlovian fear conditioning was examined in 80 rats. Excitotoxic lesions were made in the BLA using N-methyl-D-aspartate 7 days before or 1, 14, or 28 days after Pavlovian fear conditioning. Conditioning consisted of three pairings of a tone with an aversive footshock in a novel chamber, and freezing behavior served as an index of conditional fear. BLA lesions abolished conditional freezing to both the contextual and acoustic conditional stimuli at all training-to-lesion intervals, and the magnitude of the impairment did not vary as a function of the training-to-lesion interval. Reacquisition training elevated levels of freezing in rats with BLA lesions but did not reduce the magnitude of their deficit in relation to that of controls. These results reveal that neurons in the BLA have an enduring role in the expression of conditional fear.

  10. Absence of effects on the rat sperm quality after subacute exposure to low doses of fungicide prochloraz.

    PubMed

    Sanabria, Marciana; Pessin, Alessandra; Zanutto, Mirella Rossitto; Perobelli, Juliana Elaine; Guerra, Marina Trevizan; Banzato, Thais Petrochelli; Borges, Cibele dos Santos; Kempinas, Wilma De Grava

    2015-01-01

    Prochloraz (PCZ) is a fungicide and androgen-receptor antagonist used worldwide in horticulture and agriculture. Pre- and perinatal exposure to this pesticide during sexual differentiation is deleterious for male offspring. Since data on the effects of PCZ on epididymal functions are scarce, and because sperm maturation occurs in this organ, the present investigation aimed to determine whether low PCZ doses administered to rats during the phase of sperm transit through the epididymis might affect the morphophysiology of this organ and sperm quality. Adult male Wistar rats were assigned to 4 different groups: 0 (control, vehicle) or 10, 15, or 30 mg/kg bw/d PCZ diluted in corn oil administered orally for 4 consecutive days. Morphofunctional parameters of the male reproductive tract, hormone concentrations, sperm evaluations, and fertility and histopathologic analysis of testis and epididymis were assessed. There were no statistically significant differences between treated and control groups in relation to all evaluated parameters. Data demonstrated show that PCZ exposure for a brief 4-d exposure and low doses did not produce reproductive toxicity or compromise sperm quality in adult rats.

  11. 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…

  12. 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.

  13. 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

  14. The metabolic clearance of progesterone in the pregnant rat: Absence of a physiological role for the lung

    SciTech Connect

    Waddell, B.J.; Bruce, N.W.

    1989-06-01

    The metabolic clearance rate (MCR) of progesterone is among the highest for all steroid hormones studied, yet it is difficult to apportion this high MCR to specific organ contributions. The isolated lung has been shown to metabolize progesterone, and since this tissue receives the entire cardiac output, potentially it could make a major contribution to the overall MCR. This possibility was examined in the present study by measuring lung extraction of (3H)progesterone under steady-state conditions in the intact pregnant rat. Anesthetized rats (n = 6) were infused with (3H)progesterone via a femoral vein for 100 min on Day 16 of pregnancy. After the onset of steady state (40 min), four blood samples were obtained at 20-min intervals from the right ventricle and from the aorta, and the concentrations of (3H)progesterone and its metabolites were determined. Throughout the sampling period, mean arterial pressure and heart rate remained stable (two-way analysis of variance), as did the production rate (3.76 +/- 0.35 mg/day; mean +/- SEM) and the MCR (34.8 +/- 3.5 ml/min) of progesterone. Despite this high rate of clearance, there was no difference between the concentration of (3H)progesterone in arterial and right ventricular blood, indicating no net extraction of progesterone during passage through the lung. Furthermore, there was no change in the concentration of either lipid-soluble or aqueous-soluble (3H)progesterone metabolites during trans-lung passage. These observations demonstrate that the lung does not contribute to the MCR of progesterone when measured under physiological and steady-state conditions. Therefore, the relationship, MCR (ml/min) = whole-body extraction (%) x cardiac output (ml/min), is upheld for progesterone in the rat.

  15. Absence of repeated-trial tolerance to the anxiolytic-like effects of chlordiazepoxide in the rat triple test.

    PubMed

    Wehrmeister, Thaize D; Izídio, Geison S; Pereira, Elayne; Izídio, Gustavo; Ramos, André

    2010-12-01

    The triple test, recently developed to assess anxiety-related behaviors in rodents, combines three widely used behavioral tests: the open field (OF), elevated plus maze (EPM) and light/dark box (LDB). The EPM and LDB, individually, are normally sensitive to the anxiolytic effects of benzodiazepines only in the first trial, due to the phenomenon of one-trial tolerance, which limits their use in longitudinal studies. The main objective of the present investigation was to verify whether the anxiolytic-like effects of chlordiazepoxide (CDZ), previously observed in naive animals submitted to the triple test, would persist after repeated testing. To this end, three experiments were carried out where male Wistar rats received CDZ (10mg/kg) 30min before the triple test for 2, 3 or 20 consecutive days. Except for the first day of drug treatment following a previous test experience in an undrugged state, CDZ had enduring anxiolytic-like effects under all schedules, promoting an increase in the exploration of the EPM open arms (and in some cases of the white compartment of the LDB), without affecting the number of closed-arm entries. The finding that rats did not develop tolerance to CDZ even with chronic treatment and repeated exposures to the triple test suggests that this new device is a promising tool to be used in longitudinal studies involving pharmacological manipulations of anxiety-related behaviors.

  16. 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

  17. Restoration of Calbindin After Fetal Hippocampal CA3 Cell Grafting Into the Injured Hippocampus in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Shetty, Ashok K.; Hattiangady, Bharathi

    2013-01-01

    Degeneration of the CA3 pyramidal and dentate hilar neurons in the adult rat hippocampus after an intracerebroventricular kainic acid (KA) administration, a model of temporal lobe epilepsy, leads to permanent loss of the calcium binding protein calbindin in major fractions of dentate granule cells and CA1 pyramidal neurons. We hypothesize that the enduring loss of calbindin in the dentate gyrus and the CA1 subfield after CA3-lesion is due to disruption of the hippocampal circuitry leading to hyperexcitability in these regions; therefore, specific cell grafts that are capable of both reconstructing the disrupted circuitry and suppressing hyper-excitability in the injured hippocampus can restore calbindin. We compared the effects of fetal CA3 or CA1 cell grafting into the injured CA3 region of adult rats at 45 days after KA-induced injury on the hippocampal calbindin. The calbindin immunoreactivity in the dentate granule cells and the CA1 pyramidal neurons of grafted animals was evaluated at 6 months after injury (i.e. at 4.5 months post-grafting). Compared with the intact hippocampus, the calbindin in “lesion-only” hippocampus was dramatically reduced at 6 months post-lesion. However, calbindin expression was restored in the lesioned hippocampus receiving CA3 cell grafts. In contrast, in the lesioned hippocampus receiving CA1 cell grafts, calbindin expression remained less than the intact hippocampus. Thus, specific cell grafting restores the injury-induced loss of calbindin in the adult hippocampus, likely via restitution of the disrupted circuitry. Since loss of calbindin after hippocampal injury is linked to hyperexcitability, re-expression of calbindin in both dentate gyrus and CA1 subfield following CA3 cell grafting may suggest that specific cell grafting is efficacious for ameliorating injury-induced hyperexcitability in the adult hippocampus. However, electrophysiological studies of KA-lesioned hippocampus receiving CA3 cell grafts are required in future

  18. Epilepsy-associated genes.

    PubMed

    Wang, Jie; Lin, Zhi-Jian; Liu, Liu; Xu, Hai-Qing; Shi, Yi-Wu; Yi, Yong-Hong; He, Na; Liao, Wei-Ping

    2017-01-01

    Development in genetic technology has led to the identification of an increasing number of genes associated with epilepsy. These discoveries will both provide the basis for including genetic tests in clinical practice and improve diagnosis and treatment of epilepsy. By searching through several databases (OMIM, HGMD, and EpilepsyGene) and recent publications on PubMed, we found 977 genes that are associated with epilepsy. We classified these genes into 4 categories according to the manifestation of epilepsy in phenotypes. We found 84 genes that are considered as epilepsy genes: genes that cause epilepsies or syndromes with epilepsy as the core symptom. 73 genes were listed as neurodevelopment-associated genes: genes associated with both brain-development malformations and epilepsy. Several genes (536) were epilepsy-related: genes associated with both physical or other systemic abnormalities and epilepsy or seizures. We found 284 additional genes putatively associated with epilepsy; this requires further verification. These integrated data will provide new insights useful for both including genetic tests in the clinical practice and evaluating the results of genetic tests. We also summarized the epilepsy-associated genes according to their function, with the goal to better characterize the association between genes and epilepsies and to further understand the mechanisms underlying epilepsy.

  19. Targeting BK (big potassium) Channels in Epilepsy

    PubMed Central

    N'Gouemo, Prosper

    2011-01-01

    Introduction Epilepsies are disorders of neuronal excitability characterized by spontaneous and recurrent seizures. Ion channels are critical for regulating neuronal excitability and, therefore, can contribute significantly to epilepsy pathophysiology. In particular, large conductance, Ca2+-activated K+ (BKCa) channels play an important role in seizure etiology. These channels are activated by both membrane depolarization and increased intracellular Ca2+. This unique coupling of Ca2+ signaling to membrane depolarization is important in controlling neuronal hyperexcitability, as outward K+ current through BKCa channels hyperpolarizes neurons. Areas covered This review focuses on BKCa channel structure-function and discusses the role of these channels in epilepsy pathophysiology. Expert opinion Loss-of-function BKCa channels contribute neuronal hyperexcitability that can lead to temporal lobe epilepsy, tonic-clonic seizures and alcohol withdrawal seizures. Similarly, BKCa channel blockade can trigger seizures and status epilepticus. Paradoxically, some mutations in BKCa channel subunit can give rise to the channel gain-of-function that leads to development of idiopathic epilepsy (primarily absence epilepsy). Seizures themselves also enhance BKCa channel currents associated with neuronal hyperexcitability, and blocking BKCa channels suppresses generalized tonic-clonic seizures. Thus, both loss-of-function and gain-of-function BKCa channels might serve as molecular targets for drugs to suppress certain seizure phenotypes including temporal lobe seizures and absence seizures, respectively. PMID:21923633

  20. [Absence of effect of the change of food context in the activity-based anorexia phenomenon in rats].

    PubMed

    Gutiérrez Domínguez, María Teresa; Pellón, Ricardo

    2008-08-01

    The goal of this study was to analyse how the context in which animals remain during the period of access to food modulates the development of activity-based anorexia in rats. For this purpose, the effect of changing the context of the activity period and the eating period was measured in terms of body weight loss, reduction in food intake and increase in physical activity. A 2 yen 2 factorial design was implemented, by having or not having access to a running wheel, and by being exposed or not exposed to a context change. Results showed that exposure to different contexts for the wheel and for the food did not affect weight loss, food intake or activity levels. These results are in line with the theoretical position of Epling and Pierce (1992) that activity is induced by the food restriction regime.

  1. [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

  2. 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

  3. Breast tumors induced by N-methyl-N-nitrosourea are damaging to bone strength, structure, and mineralization in the absence of metastasis in rats.

    PubMed

    Thorpe, Matthew P; Valentine, Rudy J; Moulton, Christopher J; Wagoner Johnson, Amy J; Evans, Ellen M; Layman, Donald K

    2011-04-01

    Current theory on the influence of breast cancer on bone describes metastasis of tumor cells to bone tissue, followed by induction of osteoclasts and bone degradation. Tumor influences on bone health in pre- or nonmetastatic models are unknown. Female rats (n = 48, 52 days old) were injected with N-methyl-N-nitrosourea (MNU) to induce breast cancer. Animals were euthanized 10 weeks later, and tumors were weighed and classified histologically. Right femurs were extracted for testing of bone mineral density (BMD) by dual X-ray absorptiometry (DXA), bone mechanical strength by three-point bending and femoral neck bending tests, and structure by micro-computed tomography (µCT). Of 48 rats, 22 developed one or more tumors in response to MNU injection by 10 weeks. Presence of any tumor predicted significantly poorer bone health in 17 of 28 measures. In tumored versus nontumored animals, BMD was adversely affected by 3%, force at failure of the femoral midshaft by 4%, force at failure of the femoral neck by 12%, and various trabecular structural parameters by 6% to 27% (all p < .05). Similarly, greater tumor burden, represented by total tumor weight, adversely correlated with bone outcomes: r = -0.51 for BMD, -0.42 and -0.35 for femur midshaft force and work at failure, and between 0.36 and 0.59 (absolute values) for trabecular architecture (all p < .05). Presence of MNU-induced tumors and total tumor burden showed a negative association with bone health of the femur in rats in the absence of metastasis. Further study is required to elucidate mechanisms for this association.

  4. Video game epilepsy.

    PubMed

    Singh, R; Bhalla, A; Lehl, S S; Sachdev, A

    2001-12-01

    Reflex epilepsy is the commonest form of epilepsy in which seizures are provoked by specific external stimulus. Photosensitive reflex epilepsy is provoked by environmental flicker stimuli. Video game epilepsy is considered to be its variant or a pattern sensitive epilepsy. The mean age of onset is around puberty and boys suffer more commonly as they are more inclined to play video games. Television set or computer screen is the commonest precipitants. The treatment remains the removal of the offending stimulus along with drug therapy. Long term prognosis in these patients is better as photosensitivity gradually declines with increasing age. We present two such case of epilepsy induced by video game.

  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. Epilepsy and electromagnetic fields: effects of simulated atmospherics and 100-Hz magnetic fields on audiogenic seizure in rats

    NASA Astrophysics Data System (ADS)

    Juutilainen, J.; Björk, E.; Saali, K.

    1988-03-01

    In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% ( P<0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.

  7. Cannabinoid and nitric oxide signaling interplay in the modulation of hippocampal hyperexcitability: Study on electrophysiological and behavioral models of temporal lobe epilepsy in the rat.

    PubMed

    Carletti, F; Gambino, G; Rizzo, V; Ferraro, G; Sardo, P

    2015-09-10

    A growing bulk of evidence suggests that cannabinoid system plays a pivotal role in the control of hyperexcitability phenomena. Notwithstanding, the anticonvulsant action of cannabinoids has not been fully addressed, in particular the involvement of potential cellular neuromodulators, for instance nitric oxide. In the current study, we focused on two distinct rat models of temporal lobe epilepsy, the Maximal Dentate Activation and the pilocarpine-induced acute seizures, providing both electrophysiological and behavioral data on cannabinoid and nitrergic system interplay. We evaluated the antiepileptic effects of 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), a CB agonist, and of 7-Nitroindazole (7NI), a preferential neuronal nitric oxide synthase (nNOS) inhibitor, at different doses, alone and in combination. MDA study showed that these drugs protected animals in a dose-dependent manner from electrically induced epileptiform discharges. In pilocarpine model, a dose-related activity of 7NI and WIN: a) decreased the behavioral scoring, used to describe the severity of chemically induced acute seizures; b) affected latency of the onset of acute convulsions; c) dampened mortality rate. Interestingly, the combination of the treatments brought to light that individually ineffective doses of WIN turn into effective when nNOS activity is pharmacologically inhibited in both experimental conditions. This effect is mediated by CB1 receptor since the co-administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a CB1 receptor specific antagonist, thwarted the 7NI-WIN convergent action. In the light of this, our findings suggest a putative antagonism between CBr-activated pathway and NO signaling in the context of neuronal hyperexcitability and contribute to elucidate possible synaptic processes underlying neuroprotective

  8. Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

    PubMed

    Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

    2015-02-01

    The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of

  9. 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

  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. AMPA receptors in the rat and primate hippocampus: a possible absence of GluR2/3 subunits in most interneurons.

    PubMed

    Leranth, C; Szeidemann, Z; Hsu, M; Buzsáki, G

    1996-02-01

    Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are assembled from the four subunits GluR1, 2, 3, 4 (or GluRA, B, C, D). AMPA channels that do not contain the GluR2 subunit are permeable to calcium. Recent studies indicate that excitotoxic as well as epileptic and ischemic cell damage may be mediated not only by N-methyl-Daspartate receptors, but also by AMPA receptors. The majority of interneurons in the hippocampus are resistant, but subsets of interneurons are consistently damaged in different disease states. Single immunolabeling using antibodies against AMPA receptor subunits, together with double immunolabeling for calcium-binding proteins (parvalbumin, calbindin and calretinin) and the neuropeptide somatostatin, were performed to study GluR1-4 immunoreactivity in interneuronal populations and principal cells. The ultrastructure of GluR1-4 labeled neurons was also examined using electron microscopy. With the exception of calbindin-positive interneurons, GluR2/3 was absent from hippocampal interneurons in both rat and monkey. In the rat, interneurons were more strongly immunoreactive against GluR1 than principal cells. In the monkey, immunoreactivity for GluR4 in interneurons was stronger than for GluR1. All GluR subunits were confined to spines, dendritic membrane and cytoplasm surrounding the nucleus but absent from axons and presynaptic terminals. Our findings suggest that hippocampal principal cells and interneurons express different complements of AMPA receptor subunits. Furthermore, the absence of GluR2 and/or GluR3 in both vulnerable and resistant interneurons subtypes indicates that knowledge of receptor subunit composition is not sufficient to predict neuronal vulnerability.

  13. Effects of Repeated Morphine on Intracranial Self-Stimulation in Male Rats In the Absence or Presence of a Noxious Pain Stimulus

    PubMed Central

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

    2015-01-01

    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 three 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 six 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

  14. Genetics of pediatric epilepsy.

    PubMed

    Hani, Abeer J; Mikati, Husam M; Mikati, Mohamad A

    2015-06-01

    As the genetic etiologies of an expanding number of epilepsy syndromes are revealed, the complexity of the phenotype genotype correlation increases. As our review will show, multiple gene mutations cause different epilepsy syndromes, making identification of the specific mutation increasingly more important for prognostication and often more directed treatment. Examples of that include the need to avoid specific drugs in Dravet syndrome and the ongoing investigations of the potential use of new directed therapies such as retigabine in KCNQ2-related epilepsies, quinidine in KCNT1-related epilepsies, and memantine in GRIN2A-related epilepsies.

  15. Epilepsy and autism: is there a special relationship?

    PubMed

    Berg, Anne T; Plioplys, Sigita

    2012-03-01

    Increasingly, there has been an interest in the association between epilepsy and autism. The high frequency of autism in some of the early-onset developmental encephalopathic epilepsies is frequently cited as evidence of the relationship between autism and epilepsy. While these specific forms of epilepsy carry a higher-than-expected risk of autism, most, if not all, of the association may be due to intellectual disability (ID). The high prevalence of interictal EEG discharges in children with autism is also cited as further evidence although errors in the diagnosis of epilepsy seem to account for at least part of those findings. The prevalence of ID is substantially elevated in children with either epilepsy or autism. In the absence of ID, there is little evidence of a substantial, if any, increased risk of autism in children with epilepsy. Further, although the reported prevalence of autism has increased over the last several years, much of this increase may be attributable to changes in diagnostic practices, conceptualization of autism in the presence of ID, and laws requiring provision of services for children with autism. In the context of these temporal trends, any further efforts to tease apart the relationships between epilepsy, ID, and autism will have to address head-on the accuracy of diagnosis of all three conditions before we can determine whether there is, indeed, a special relationship between autism and epilepsy.

  16. Myoclonus and epilepsies.

    PubMed

    Fejerman, N

    1997-01-01

    The possible associations of myoclonic phenomenae, progressive or non-progressive encephalopathies and epileptic features are reviewed, with special emphasis on pediatric age. This leads to recognize the following five groups of conditions: (1) Myoclonus without encephalopathy and without epilepsy; (2) Encephalopathies with non-epileptic myoclonus; (3) Progressive encephalopathies presenting myoclonus seizures of epileptic syndromes (Progressive myoclonus epilepsies); (4) Epileptic encephalopathies with myoclonic seizures; (5) Myoclonic epilepsies. Within the first group, which also includes physiologic myoclonus, a more thorough description of "Benign sleep myoclonus of newborn" and "Benign myoclonus of early infancy" is given. Characteristics of group 2 are "Kinsbourne Syndrome" and certain types of "Hyperekplexia" which pose interesting differential diagnosis with stimulus-sensitive epilepsies. In group 3, the concept of progressive encephalopathies is stressed. The fourth group refers to severe epilepsies, mainly on infancy and childhood, which lead to mental retardation irrespective of their aetiology. Group 5 comprises the true myoclonic epilepsies, differentiating syndromes recognized as idiopathic--such as "Benign myoclonic epilepsy of infancy" and "Juvenile myoclonic epilepsy"--from those which are cryptogenic and carry a more cautious prognosis--as "Cryptogenic myoclonic and myoclonoastatic epilepsies" and "Severe myoclonic epilepsy of infancy". Other epileptic syndromes not usually considered as myoclonic epilepsies, but presenting sometimes as myoclonic seizures, are finally referred.

  17. [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.

  18. Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy.

    PubMed

    Mendonça, Fabricio N; Santos, Luiz E C; Rodrigues, Antônio M; Gomes da Silva, Sérgio; Arida, Ricardo M; da Silveira, Gilcélio A; Scorza, Fulvio A; Almeida, Antônio-Carlos G

    2017-01-01

    Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group. Notably, a larger number of newborn granule cells exhibiting morphological characteristics indicative of correct targeting into the hippocampal circuitry and the absence of basal dendrite projections was also observed in the epileptic animals subjected to physical exercise compared to the epileptic animals. The results described here could represent a positive interference of the physical exercise on the neurogenesis process in subjects with chronic epilepsy. The results may also help to reinterpret the benefits of the physical exercise in alleviating symptoms of depression and cognitive dysfunction.

  19. Physical Exercise Restores the Generation of Newborn Neurons in an Animal Model of Chronic Epilepsy

    PubMed Central

    Mendonça, Fabricio N.; Santos, Luiz E. C.; Rodrigues, Antônio M.; Gomes da Silva, Sérgio; Arida, Ricardo M.; da Silveira, Gilcélio A.; Scorza, Fulvio A.; Almeida, Antônio-Carlos G.

    2017-01-01

    Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group. Notably, a larger number of newborn granule cells exhibiting morphological characteristics indicative of correct targeting into the hippocampal circuitry and the absence of basal dendrite projections was also observed in the epileptic animals subjected to physical exercise compared to the epileptic animals. The results described here could represent a positive interference of the physical exercise on the neurogenesis process in subjects with chronic epilepsy. The results may also help to reinterpret the benefits of the physical exercise in alleviating symptoms of depression and cognitive dysfunction. PMID:28298884

  20. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    PubMed

    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

  1. 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

  2. Autism and epilepsy

    PubMed Central

    Larsson, Henrik; Lichtenstein, Paul; Almqvist, Catarina; Hultman, Christina M.; Tomson, Torbjörn; Ludvigsson, Jonas F.

    2016-01-01

    Objective: To investigate the risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives to determine shared etiology. Methods: Through the Swedish Patient Register, we identified 85,201 individuals with epilepsy, as well as all their siblings (n = 80,511) and offspring (n = 98,534). Each individual with epilepsy was compared with 5 controls, matched for age, sex, calendar period, and county, while siblings and offspring were compared with siblings and offspring of controls. We excluded siblings and offspring with epilepsy. Using Cox regression, we calculated hazard ratios (HRs) for future diagnosis of ASD. Logistic regression was applied to calculate odds ratios (ORs) for prior diagnosis of ASD. Results: During follow-up, 1,381 (1.6%) individuals with epilepsy and 700 (0.2%) controls were diagnosed with ASD. Individuals with epilepsy were therefore at increased risk of future ASD (HR 10.49, 95% confidence interval [CI] 9.55–11.53), with the highest risk seen in individuals diagnosed with epilepsy in childhood. Both siblings (HR 1.62, 95% CI 1.43–1.83) and offspring (HR 1.64, 95% CI 1.46–1.84) of epilepsy patients were at increased risk of ASD. The risk in the offspring was particularly high in mothers with epilepsy (HR 1.91; 95% CI 1.63–2.23). Epilepsy was also associated with a prior diagnosis of ASD (OR 4.56, 95% CI 4.02–5.18). Conclusions: Individuals with epilepsy are at increased risk of ASD, especially if epilepsy appears in childhood. Further, ASD is more common in the siblings and offspring of individuals with epilepsy, suggesting shared etiology. PMID:27306624

  3. Genetics of epilepsy

    PubMed Central

    Vadlamudi, Lata; Milne, Roger L.; Lawrence, Kate; Heron, Sarah E.; Eckhaus, Jazmin; Keay, Deborah; Connellan, Mary; Torn-Broers, Yvonne; Howell, R. Anne; Mulley, John C.; Scheffer, Ingrid E.; Dibbens, Leanne M.; Hopper, John L.

    2014-01-01

    Objective: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicability of the 2010 International League Against Epilepsy (ILAE) organization of epilepsy syndromes, and to integrate molecular genetics with phenotypic analyses. Methods: A total of 558 twin pairs suspected to have epilepsy were ascertained from twin registries (69%) or referral (31%). Casewise concordance estimates were calculated for epilepsy syndromes. Epilepsies were then grouped according to the 2010 ILAE organizational scheme. Molecular genetic information was utilized where applicable. Results: Of 558 twin pairs, 418 had confirmed seizures. A total of 534 twin individuals were affected. There were higher twin concordance estimates for monozygotic (MZ) than for dizygotic (DZ) twins for idiopathic generalized epilepsies (MZ = 0.77; DZ = 0.35), genetic epilepsy with febrile seizures plus (MZ = 0.85; DZ = 0.25), and focal epilepsies (MZ = 0.40; DZ = 0.03). Utilizing the 2010 ILAE scheme, the twin data clearly demonstrated genetic influences in the syndromes designated as genetic. Of the 384 tested twin individuals, 10.9% had mutations of large effect in known epilepsy genes or carried validated susceptibility alleles. Conclusions: Twin studies confirm clear genetic influences for specific epilepsies. Analysis of the twin sample using the 2010 ILAE scheme strongly supported the validity of grouping the “genetic” syndromes together and shows this organizational scheme to be a more flexible and biologically meaningful system than previous classifications. Successful selected molecular testing applied to this cohort is the prelude to future large-scale next-generation sequencing of epilepsy research cohorts. Insights into genetic architecture provided by twin studies provide essential data for optimizing such approaches. PMID:25107880

  4. Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations.

    PubMed

    Dufour, F; Nalecz, K A; Nalecz, M J; Nehlig, A

    2001-07-01

    The occurrence of absence seizures might be due to a disturbance of the balance between excitatory and inhibitory neurotransmissions in the thalamo-cortical loop. In this study, we explored the consequences of buffering the glutamate content of brain cells on the occurrence and duration of seizures in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a genetic model of generalized non-convulsive epilepsy. Branched-chain amino acids (BCAAs) and alpha-ketoisocaproate (alpha-KIC), the ketoacid of leucine were repeatedly shown to have a critical role in brain glutamate metabolism. Thus, GAERS were injected by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) route with these compounds, then the effects on seizures were evaluated on the electroencephalographic recording. We also measured the concentration of amino acids in thalamus and cortex after an i.p. injection of leucine or alpha-KIC. Intracerebroventricular injections of leucine or alpha-KIC did not influence the occurrence of seizures, possibly because the substances reached only the cortex. BCAAs and alpha-KIC, injected intraperitoneally, increased the number of seizures whereas they had only a slight effect on their duration. Leucine and alpha-KIC decreased the concentration of glutamate in thalamus and cortex without affecting GABA concentrations. Thus, BCAAs and alpha-KIC, by decreasing the effects of glutamatergic neurotransmission could facilitate those of GABAergic neurotransmission, which is known to increase the occurrence of seizures in GAERS.

  5. Quercetin Induces Dose-Dependent Differential Morphological and Proliferative Changes in Rat Uteri in the Presence and in the Absence of Estrogen

    PubMed Central

    Shahzad, Huma; Giribabu, Nelli; Sekaran, Muniandy

    2015-01-01

    Abstract Quercetin could have profound effects on uterine morphology and proliferation, which are known to be influenced by estrogen. This study investigated the effect of quercetin on these uterine parameters in the presence and in the absence of estrogen. Ovariectomized adult female rats received peanut oil, quercetin (10, 50, and 100 mg/kg/day), estrogen, or estrogen+quercetin (10, 50, or 100 mg/kg/day) treatment for 7 consecutive days. At the end of the treatment, uteri were harvested for histological and molecular biological analyses. Distribution of proliferative cell nuclear antigen (PCNA) protein in the uterus was observed by immunohistochemistry. Levels of expression of PCNA protein and mRNA in uterine tissue homogenates were determined by Western blotting and real-time polymerase chain reaction, respectively. Our findings indicated that administration of 10 mg/kg/day of quercetin either alone or with estrogen resulted in decreased uterine expression of PCNA protein and mRNA with the percentage of PCNA-positive cells in uterine luminal and glandular epithelia markedly reduced compared with estrogen-only treatment. Changes in uterine morphology were the opposite of changes observed following estrogen treatment. Treatment with 100 mg/kg/day of quercetin either alone or with estrogen resulted in elevated PCNA protein and mRNA expression. In addition, the percentages of PCNA-positive cells in the epithelia, which line the lumen and glands, were increased with morphological features mimicking changes that occur following estrogen treatment. Following 50 mg/kg/day quercetin treatment, the changes observed were in between those changes that occur following 10 and 100 mg/kg/day quercetin treatment. In conclusion, changes in uterine morphology and proliferation following 10 mg/kg/day quercetin treatment could be attributed to quercetin's antiestrogenic properties, while changes that occur following 100 mg/kg/day quercetin treatment could be

  6. Quercetin Induces Dose-Dependent Differential Morphological and Proliferative Changes in Rat Uteri in the Presence and in the Absence of Estrogen.

    PubMed

    Shahzad, Huma; Giribabu, Nelli; Sekaran, Muniandy; Salleh, Naguib

    2015-12-01

    Quercetin could have profound effects on uterine morphology and proliferation, which are known to be influenced by estrogen. This study investigated the effect of quercetin on these uterine parameters in the presence and in the absence of estrogen. Ovariectomized adult female rats received peanut oil, quercetin (10, 50, and 100 mg/kg/day), estrogen, or estrogen+quercetin (10, 50, or 100 mg/kg/day) treatment for 7 consecutive days. At the end of the treatment, uteri were harvested for histological and molecular biological analyses. Distribution of proliferative cell nuclear antigen (PCNA) protein in the uterus was observed by immunohistochemistry. Levels of expression of PCNA protein and mRNA in uterine tissue homogenates were determined by Western blotting and real-time polymerase chain reaction, respectively. Our findings indicated that administration of 10 mg/kg/day of quercetin either alone or with estrogen resulted in decreased uterine expression of PCNA protein and mRNA with the percentage of PCNA-positive cells in uterine luminal and glandular epithelia markedly reduced compared with estrogen-only treatment. Changes in uterine morphology were the opposite of changes observed following estrogen treatment. Treatment with 100 mg/kg/day of quercetin either alone or with estrogen resulted in elevated PCNA protein and mRNA expression. In addition, the percentages of PCNA-positive cells in the epithelia, which line the lumen and glands, were increased with morphological features mimicking changes that occur following estrogen treatment. Following 50 mg/kg/day quercetin treatment, the changes observed were in between those changes that occur following 10 and 100 mg/kg/day quercetin treatment. In conclusion, changes in uterine morphology and proliferation following 10 mg/kg/day quercetin treatment could be attributed to quercetin's antiestrogenic properties, while changes that occur following 100 mg/kg/day quercetin treatment could be attributed to

  7. 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.

  8. Headache and epilepsy.

    PubMed

    Bauer, P R; Carpay, J A; Terwindt, G M; Sander, J W; Thijs, R J; Haan, J; Visser, G H

    2013-08-01

    Headache and epilepsy often co-occur. Epidemiologic studies conducted in the past few years reinforce the notion of a bi-directional association between migraine and epilepsy. Data on an association between headache (in general) and epilepsy, however, are less clear. Peri-ictal headache often presents with migraine-like symptoms and can be severe. A correct diagnosis and management are paramount. It was demonstrated that cortical hyperexcitability may underlie both epilepsy and migraine. A recent study linked spreading depolarisation, the supposed underlying pathophysiological mechanism of migraine with aura, to epilepsy. Although this study was carried out in patients who had suffered a subarachnoid haemorrhage, the finding may shed light on pathophysiological mechanisms common to epilepsy and migraine.

  9. Pharmacoresistant epilepsy and nanotechnology.

    PubMed

    Rosillo-de la Torre, Argelia; Luna-Bárcenas, Gabriel; Orozco-Suárez, Sandra; Salgado-Ceballos, Hermelinda; García, Perla; Lazarowski, Alberto; Rocha, Luisa

    2014-06-01

    Epilepsy is one of the most common chronic neurological disorders. Furthermore, it is associated to diminished health-related quality of life and is thus considered a major public health problem. In spite of the large number of available and ongoing development of several new antiepileptic drugs (AEDs), a high percentage of patients with epilepsy (35-40%) are resistant to pharmacotherapy. A hypothesis to explain pharmacoresistance in epilepsy suggests that overexpression of multidrug resistance proteins, such as P-glycoprotein, on the endothelium of the blood brain barrier represents a challenge for effective AED delivery and concentration levels in the brain. Proven therapeutic strategies to control pharmacoresistant epilepsy include epilepsy surgery and neuromodulation. Unfortunately, not all patients are candidates for these therapies. Nanotechnology represents an attractive strategy to overcome the limited brain access of AEDs in patients with pharmacoresistant epilepsy. This manuscript presents a review of evidences supporting this idea.

  10. Grey matter heterotopia: an unusual association of intractable epilepsy.

    PubMed

    Stafford Johnson, D B; Brennan, P; Dwyer, A J; Toland, J

    1997-01-01

    Heterotopic grey matter is an abnormality of neuronal migration that has been reported in association with refractory epilepsy. In this study we reviewed the magnetic resonance (MR) imaging records of all patients undergoing MR scanning for evaluation of intractable epilepsy and identified sixteen patients who had grey matter heterotopia. The distribution of the grey matter heterotopia was periventricular in 9 patients, laminar in 3 and was in a "band" form in 4 patients. Congenital anomalies associated with grey matter heterotopia in this study included polymicrogyria in one patient and absence of the corpus callosum in 2 patients. Grey matter heterotopia is an important MR finding in patients with intractable epilepsy.

  11. Mobile EEG in epilepsy.

    PubMed

    Askamp, Jessica; van Putten, Michel J A M

    2014-01-01

    The sensitivity of routine EEG recordings for interictal epileptiform discharges in epilepsy is limited. In some patients, inpatient video-EEG may be performed to increase the likelihood of finding abnormalities. Although many agree that home EEG recordings may provide a cost-effective alternative to these recordings, their use is still not introduced everywhere. We surveyed Dutch neurologists and patients and evaluated a novel mobile EEG device (Mobita, TMSi). Key specifications were compared with three other current mobile EEG devices. We shortly discuss algorithms to assist in the review process. Thirty percent (33 out of 109) of Dutch neurologists reported that home EEG recordings are used in their hospital. The majority of neurologists think that mobile EEG can have additional value in investigation of unclear paroxysms, but not in the initial diagnosis after a first seizure. Poor electrode contacts and signal quality, limited recording time and absence of software for reliable and effective assistance in the interpretation of EEGs have been important constraints for usage, but in recent devices discussed here, many of these problems have been solved. The majority of our patients were satisfied with the home EEG procedure and did not think that our EEG device was uncomfortable to wear, but they did feel uneasy wearing it in public.

  12. Epilepsy, psychiatry, and neurology.

    PubMed

    Reynolds, Edward H; Trimble, Michael R

    2009-03-01

    This article reviews the relationship between the psychiatry and neurology of epilepsy, especially in the last 100 years. Throughout most of its recorded history of 3 to 4 millennia epilepsy has been viewed as a supernatural or mental disorder. Although first suggested by Hippocrates in the 5th century B.C., the concept of epilepsy as a brain disorder only began to take root in the 17th and 18th centuries. The discipline of neurology emerged from "nervous disorders" or neuropsychiatry in the late 19th century, when vascular theories of epilepsy predominated. By the turn of the 19th century psychiatry and neurology were diverging and epilepsy remained to some extent in both disciplines. It was only in the middle of the 20th century with the development of electromagnetic theories of epilepsy that the concept of epilepsy per se as a neurological disorder was finally adopted in international classifications of disease. This was associated with a refined definition of the ictal, pre-, post-, and interictal psychological disorders of epilepsy, which have contributed to a renaissance of neuropsychiatry. At the beginning of the 21st century and the centenary of the ILAE psychiatry and neurology have been converging again, led in some respects by epilepsy, which has provided several useful models of mental illness and a bridge between the two disciplines.

  13. Epilepsy: Indian perspective

    PubMed Central

    Santhosh, Nandanavana Subbareddy; Sinha, Sanjib; Satishchandra, Parthasarathy

    2014-01-01

    There are 50 million people living with epilepsy worldwide, and most of them reside in developing countries. About 10 million persons with epilepsy are there in India. Many people with active epilepsy do not receive appropriate treatment for their condition, leading to large treatment gap. The lack of knowledge of antiepileptic drugs, poverty, cultural beliefs, stigma, poor health infrastructure, and shortage of trained professionals contribute for the treatment gap. Infectious diseases play an important role in seizures and long-term burden causing both new-onset epilepsy and status epilepticus. Proper education and appropriate health care services can make tremendous change in a country like India. There have been many original researches in various aspects of epilepsy across India. Some of the geographically specific epilepsies occur only in certain regions of our country which have been highlighted by authors. Even the pre-surgical evaluation and epilepsy surgery in patients with drug-resistant epilepsy is available in many centers in our country. This article attempts to provide a complete preview of epilepsy in India. PMID:24791085

  14. Approaches to refractory epilepsy

    PubMed Central

    Engel, Jerome

    2014-01-01

    Epilepsy is one of the most common serious neurological conditions, and 30 to 40% of people with epilepsy have seizures that are not controlled by medication. Patients are considered to have refractory epilepsy if disabling seizures continue despite appropriate trials of two antiseizure drugs, either alone or in combination. At this point, patients should be referred to multidisciplinary epilepsy centers that perform specialized diagnostic testing to first determine whether they are, in fact, pharmacoresistant, and then, if so, offer alternative treatments. Apparent pharmacoresistance can result from a variety of situations, including noncompliance, seizures that are not epileptic, misdiagnosis of the seizure type or epilepsy syndrome, inappropriate use of medication, and lifestyle issues. For patients who are pharmacoresistant, surgical treatment offers the best opportunity for complete freedom from seizures. Surgically remediable epilepsy syndromes have been identified, but patients with more complicated epilepsy can also benefit from surgical treatment and require more specialized evaluation, including intracranial EEG monitoring. For patients who are not surgical candidates, or who are unwilling to consider surgery, a variety of other alternative treatments can be considered, including peripheral or central neurostimulation, ketogenic diet, and complementary and alternative approaches. When such alternative treatments are not appropriate or effective, quality of life can still be greatly improved by the psychological and social support services offered by multidisciplinary epilepsy centers. A major obstacle remains the fact that only a small proportion of patients with refractory epilepsy are referred for expert evaluation and treatment. PMID:24791078

  15. EPILEPSY AND MENTAL RETARDATION

    PubMed Central

    Madhavan, Thuppal; Narayan, Jayanthi

    1992-01-01

    Epilepsy is one of the most frequently associated conditions with mental retardation which interferes with the learning process. Vie present study investigates the 1207 cases (Male -8I4, Female-393) registered at NIMH, Secunderabad, over a period of two years. Vie factors studied were the prevalence of epilepsy, degree of mental retardation, aetiology and associated factors. Ten mentally retarded persons with epilepsy were followed up longitudinally to study the effect of epilepsy on learning. It was observed that an attack of seizure resulted in a setback in the learning of skills. The results are discussed. PMID:21776089

  16. Epilepsy: Indian perspective.

    PubMed

    Santhosh, Nandanavana Subbareddy; Sinha, Sanjib; Satishchandra, Parthasarathy

    2014-03-01

    There are 50 million people living with epilepsy worldwide, and most of them reside in developing countries. About 10 million persons with epilepsy are there in India. Many people with active epilepsy do not receive appropriate treatment for their condition, leading to large treatment gap. The lack of knowledge of antiepileptic drugs, poverty, cultural beliefs, stigma, poor health infrastructure, and shortage of trained professionals contribute for the treatment gap. Infectious diseases play an important role in seizures and long-term burden causing both new-onset epilepsy and status epilepticus. Proper education and appropriate health care services can make tremendous change in a country like India. There have been many original researches in various aspects of epilepsy across India. Some of the geographically specific epilepsies occur only in certain regions of our country which have been highlighted by authors. Even the pre-surgical evaluation and epilepsy surgery in patients with drug-resistant epilepsy is available in many centers in our country. This article attempts to provide a complete preview of epilepsy in India.

  17. Surgical treatment for epilepsy

    PubMed Central

    Engel, Jerome; Wiebe, Samuel; Radhakrishnan, Kurupath; Palmini, André

    2016-01-01

    Surgical treatment for epilepsy remains highly underutilized: in the United States, there has been no increase in the number of surgical procedures performed annually since 19901; for most patients referred, the average duration of epilepsy is 22 years2; and there has been no change in this delay to surgery3, despite two randomized controlled trials4, 5 and an American Academy of Neurology practice parameter that recommended surgery as the treatment of choice for medically refractory temporal lobe epilepsy6. This session addressed issues relevant to increasing the availability of epilepsy surgery, particularly in countries with limited resources.

  18. NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy

    PubMed Central

    Rothan, Hussin A.; Amini, Elham; Faraj, Fadihl L.; Golpich, Mojtaba; Teoh, Teow Chong; Gholami, Khadijeh; Yusof, Rohana

    2017-01-01

    N-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants. PMID:28358047

  19. Prevalence and characteristics of visual aura in idiopathic generalized epilepsy.

    PubMed

    Gungor-Tuncer, Ozlem; Baykan, Betul; Altindag, Ebru; Bebek, Nerses; Gurses, Candan; Gokyigit, Aysen

    2012-12-01

    Some patients with idiopathic/genetic generalized epilepsy (IGE) experience visual aura, which can confuse the diagnosis. We sought to determine the frequency and characteristics of visual auras in IGE patients. Among the 176 IGE patients, 4 men and 7 women reported visual auras (mean age - 24 years). Syndromic diagnoses were juvenile myoclonic epilepsy in four, eyelid myoclonia with absences (EMA) in three, juvenile absence epilepsy in three, and other in one. Visual auras consisted of flashing lights, macropsia, illusional movements, and blindness. Eyelid myoclonia with absences was significantly more common in the group with visual aura (3 of 11 patients vs. 8 of 165 IGE patients; P=0.02). Furthermore, photosensitivity was found significantly more common in IGE patients with visual aura (90% vs 46% of the total IGE patients) (P=0.004). In conclusion, the visual auras do not exclude a diagnosis of IGE. The presence of visual aura in the EMA syndrome is also remarkable.

  20. 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…

  1. Epilepsy and oral care.

    PubMed

    Fiske, Janice; Boyle, Carole

    2002-05-01

    Epilepsy is a common symptom of an underlying neurological disorder. The seizures can take a variety of forms. Both the condition and its medical management can affect oral health. Prevention of oral disease and carefully planned dental treatment are essential to the well-being of people with epilepsy.

  2. Sex, epilepsy, and epigenetics

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2014-01-01

    Epilepsy refers to a heterogeneous group of disorders that are associated with a wide range of pathogenic mechanisms, seizure manifestations, comorbidity profiles, and therapeutic responses. These characteristics are all influenced quite significantly by sex. As with other conditions exhibiting such patterns, sex differences in epilepsy are thought to arise—at the most fundamental level—from the “organizational” and “activational” effects of sex hormones as well as from the direct actions of the sex chromosomes. However, our understanding of the specific molecular, cellular, and network level processes responsible for mediating sex differences in epilepsy remains limited. Because increasing evidence suggests that epigenetic mechanisms are involved both in epilepsy and in brain sexual dimorphism, we make the case here that analyzing epigenetic regulation will provide novel insights into the basis for sex differences in epilepsy. PMID:24998474

  3. 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".

  4. Infections, inflammation and epilepsy

    PubMed Central

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

    2016-01-01

    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

  5. Epilepsy: Asia versus Africa.

    PubMed

    Bhalla, Devender; Tchalla, Achille Edem; Marin, Benoît; Ngoungou, Edgard Brice; Tan, Chong Tin; Preux, Pierre-Marie

    2014-09-01

    Is epilepsy truly an "African ailment"? We aimed to determine this, since international health agencies often refer to epilepsy as an African disease and the scientific literature has spoken the same tone. Various published materials, mainly reports, articles, were used to gather Asian and African evidence on various aspects of epilepsy and many of its risk and associated factors. Our results suggest that in no way can epilepsy be considered as an African ailment and such characterization is most likely based on popular beliefs rather than scientific evidence. In comparison to Africa, Asia has a 5.0% greater burden from all diseases, and is 17.0% more affected from neuropsychiatric disorders (that include epilepsy). Given that more countries in Asia are transitioning, there may be large demographic and lifestyle changes in the near future. However these changes are nowhere close to those expected in Africa. Moreover, 23 million Asians have epilepsy in comparison to 3.3 million Africans and 1.2 million sub-Saharan Africans. In comparison to Africa, Asia has more untreated patients, 55.0% more additional epilepsy cases every year, because of its larger population, with greater treatment cost and possibly higher premature mortality. Of several associated factors discussed herein, many have more importance for Asia than Africa. The current state of epilepsy in Asia is far less than ideal and there is an urgent need to recognize and accept the importance of epilepsy in Asia. In no way can epilepsy be considered as an African ailment. This is most likely based on popular beliefs rather than scientific evidence. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

  6. 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.

  7. 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

  8. [Migraine and epilepsy].

    PubMed

    Tsuji, Sadatoshi

    2014-01-01

    Migraine and epilepsy are both common episodic disorders that share many clinical features and underlying pathophysiological mechanisms. The comorbidity of these two conditions is well known. However, the temporal association between migraine and epilepsy is a controversial issue, since these two conditions may occur in numerous ways. Four types of association between headache and epileptic seizure are recognized: pre-ictal headache, headache as the expression of an epileptic manifestation, post-ictal headache, and inter-ictal headache. The classification of epilepsy by the International League Against Epilepsy did not refer to the epileptic headache. On the other hand, the International Classification of Headache Disorders, 3rd edition (ICHD-3) defines three entities: migraine aura-triggered seizure which sometimes referred to as migralepsy, hemicrania epileptica, and post-ictal headache. However, ICHD-3 mentions that there is a complex and bidirectional association between migraine and epilepsy. Most of the previous reports of migralepsy corresponded to occipital seizures that mimic migraine with aura. The term migralepsy has recently been criticized. Migraine and epilepsy share several pathophysiological mechanisms which involve neurotransmitters and iron channel dysfunctions. There is the hypothesis of a shared genetic susceptibility to migraine and epilepsy. Strong support of a shared genetic basis comes from familial hemiplegic migraine.

  9. 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.

  10. Psychosocial aspects of epilepsy.

    PubMed

    Shah, Pravina

    2002-05-01

    Social attitudes towards epilepsy cause more distress to the patient and his/her near and dear ones, than the disease itself. The major psychosocial issues related to epilepsy are: Quality of medical management, overprotection, education, employment, marriage and pregnancy. Inadequate treatment is the major reason involved in psychosocial issues. Constant overprotection and pampering leads to behavioural pattern which makes epileptic patient dependent for ever. Education is hampered in epileptic persons. Teachers and students should have proper information regarding seizures. If seizures are well controlled, job opportunities increase. Employers and employees need to be educated about epilepsy. Self-employment is the best in epileptic patients. Regarding marriage, each patient is to be judged on individual merits and type of epilepsy. Society needs to be educated about the facts and consequences of epilepsy. Risk of anti-epileptic drug's usage is very insignificant compared to risk of seizures in pregnancy. So girls are advised to seek medical advice before pregnancy and during follow-up. With more and more support from the society, persons with epilepsy will have the courage and confidence to speak about themselves and their illness. It is only then that we will realise that persons with epilepsy are 'normal' or 'near-normal' and this will break the vicious cycle of stigma.

  11. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    PubMed Central

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  12. Validation of a Preclinical Drug Screening Platform for Pharmacoresistant Epilepsy.

    PubMed

    Barker-Haliski, Melissa L; Johnson, Kristina; Billingsley, Peggy; Huff, Jennifer; Handy, Laura J; Khaleel, Rizvana; Lu, Zhenmei; Mau, Matthew J; Pruess, Timothy H; Rueda, Carlos; Saunders, Gerald; Underwood, Tristan K; Vanegas, Fabiola; Smith, Misty D; West, Peter J; Wilcox, Karen S

    2017-03-16

    The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents. It is clear that this traditional screening approach has greatly expanded the number of marketed drugs available to manage the symptomatic seizures associated with epilepsy. In spite of the numerous antiseizure drugs (ASDs) on the market today, the fact remains that nearly 30% of patients are resistant to these currently available medications. To address this unmet medical need, the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) revised its approach to the early evaluation of investigational agents for the treatment of epilepsy in 2015 to include a focus on preclinical approaches to model pharmacoresistant seizures. This present report highlights the in vivo and in vitro findings associated with the initial pharmacological validation of this testing approach using a number of mechanistically diverse, commercially available antiseizure drugs, as well as several probe compounds that are of potential mechanistic interest to the clinical management of epilepsy.

  13. HMGB1-TLR4 Axis Plays a Regulatory Role in the Pathogenesis of Mesial Temporal Lobe Epilepsy in Immature Rat Model and Children via the p38MAPK Signaling Pathway.

    PubMed

    Yang, Weihong; Li, Jing; Shang, Yun; Zhao, Li; Wang, Mingying; Shi, Jipeng; Li, Shujun

    2017-02-07

    The HMGB1-TLR4 axis is activated in adult mouse models of acute and chronic seizure. Nevertheless, whether HMGB1 was involved in the pathogenesis of mesial temporal lobe epilepsy (MTLE) remains unknown. In this study, we first measured the dynamic expression patterns of HMGB1 and TLR4 in the hippocampi of a rat model and in children with MTLE, as well as the levels of TNF-α and IL-1β. In addition, HMGB1 was added to mimic the process of inflammatory response in neurons. Neuronal somatic size and dendritic length were measured by immunohistochemistry and digital imaging. The results showed that the expression of HMGB1 and TLR4 as well as the levels of TNF-α and IL-1β were higher in the three stages of MTLE development in the rat model and in the children with MTLE. HMGB1 increased the levels of TNF-α and IL-1β, upregulated the protein level of p-p38MAPK and promoted the growth of cell somatic size and dendritic length in neurons. Pre-treatment with p38MAPK inhibitor SB203580 decreased the levels of TNF-α and IL-1β, while downregulation of TLR4 significantly reduced HMGB1-induced p38MAPK signaling pathway activation. These data demonstrated that the HMGB1-TLR4 axis may play an important role in the pathogenesis of MTLE via the p38MAPK signaling pathway.

  14. 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.

  15. 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.

  16. Pediatric Absence Status Epilepticus: Prolonged Altered Mental Status in an 8-Year-Old Boy

    PubMed Central

    Sohail, Shahmir; Almubarak, Salah

    2016-01-01

    Absence status epilepticus is characterized by a prolonged state of impaired consciousness or altered sensorium with generalized electroencephalographic abnormalities. It is most commonly diagnosed in patients with known idiopathic generalized epilepsy; however, it may also be the first presentation of epilepsy. Due to the subtle and variable manifestations of the condition, absence status epilepticus may be underrecognized, particularly in children. We present the case of an 8-year-old boy who experienced two episodes of prolonged altered mental status, subsequently determined to be absence status epilepticus with idiopathic generalized epilepsy with phantom absences. We discuss the classification, pathophysiology, clinical presentation, and electroencephalographic findings of pediatric absence status epilepticus and provide a practical overview for management. PMID:28042487

  17. Heautoscopy, epilepsy, and suicide.

    PubMed Central

    Brugger, P; Agosti, R; Regard, M; Wieser, H G; Landis, T

    1994-01-01

    Heautoscopy (the doppelgänger experience), epilepsy, and suicide is a triad primarily known from literary accounts. This paper reports a patient with complex partial seizures who tried to commit suicide during the experience of heautoscopy. PMID:8021672

  18. Heautoscopy, epilepsy, and suicide.

    PubMed

    Brugger, P; Agosti, R; Regard, M; Wieser, H G; Landis, T

    1994-07-01

    Heautoscopy (the doppelgänger experience), epilepsy, and suicide is a triad primarily known from literary accounts. This paper reports a patient with complex partial seizures who tried to commit suicide during the experience of heautoscopy.

  19. Employees with Epilepsy

    MedlinePlus

    ... systems to communicate with coworkers Provide 2-way radios with texting options Use alert systems to send ... a seizure. JAN suggested using a two‑way radio. A student with epilepsy used hedge-cutters and ...

  20. Surgical Treatment of Epilepsy

    PubMed Central

    Miller, John W.; Hakimian, Shahin

    2013-01-01

    Purpose of Review: This article outlines indications for neurosurgical treatment of epilepsy, describes the presurgical workup, summarizes surgical approaches, and details expected risks and benefits. Recent Findings: There is class I evidence for the efficacy of temporal lobectomy in treating intractable seizures, and accumulating documentation that successful surgical treatment reverses much of the disability, morbidity, and excess mortality of chronic epilepsy. Summary: Chronic, uncontrolled focal epilepsy causes progressive disability and increased mortality, but these can be reversed with seizure control. Vigorous efforts to stop seizures are warranted. If two well-chosen and tolerated medication trials do not achieve seizure control, an early workup for epilepsy surgery should be arranged. If this workup definitively identifies the brain region from which the seizures arise, and this region can be removed with a low risk of disabling neurologic deficits, neurosurgery will have a much better chance of stopping seizures than further medication trials. PMID:23739107

  1. Epilepsy and bipolar disorder.

    PubMed

    Knott, Sarah; Forty, Liz; Craddock, Nick; Thomas, Rhys H

    2015-11-01

    It is well recognized that mood disorders and epilepsy commonly co-occur. Despite this, our knowledge regarding the relationship between epilepsy and bipolar disorder is limited. Several shared features between the two disorders, such as their episodic nature and potential to run a chronic course, and the efficacy of some antiepileptic medications in the prophylaxis of both disorders, are often cited as evidence of possible shared underlying pathophysiology. The present paper aims to review the bidirectional associations between epilepsy and bipolar disorder, with a focus on epidemiological links, evidence for shared etiology, and the impact of these disorders on both the individual and wider society. Better recognition and understanding of these two complex disorders, along with an integrated clinical approach, are crucial for improved evaluation and management of comorbid epilepsy and mood disorders.

  2. Epilepsy - children - discharge

    MedlinePlus

    ... activities include jogging, aerobics, moderate cross-country skiing, dancing, tennis, golf, hiking, and bowling. Games and playing ... Philadelphia, PA: Elsevier; 2016:chap 593. Read More Brain aneurysm repair Brain surgery Epilepsy - overview Seizures Stereotactic ...

  3. Mesial frontal lobe epilepsy.

    PubMed

    Unnwongse, Kanjana; Wehner, Tim; Foldvary-Schaefer, Nancy

    2012-10-01

    Mesial frontal lobe epilepsies can be divided into epilepsies arising from the anterior cingulate gyrus and those of the supplementary sensorimotor area. They provide diagnostic challenges because they often lack lateralizing or localizing features on clinical semiology and interictal and ictal scalp electroencephalographic (EEG) recordings. A number of unique semiologic features have been described over the last decade in patients with mesial frontal lobe epilepsy (FLE). There are few reports of applying advanced neurophysiologic techniques such as electrical source imaging, magnetoencephalography, EEG/functional magnetic resonance imaging, or analysis of high-frequency oscillations in patients with mesial FLE. Despite these diagnostic challenges, it seems that patients with mesial FLE benefit from epilepsy surgery to the same extent or even better than patients with FLE do, as a whole.

  4. Genetics and epilepsy

    PubMed Central

    Steinlein, Ortrud K.

    2008-01-01

    The term “epilepsy” describes a heterogeneous group of disorders, most of them caused by interactions between several or even many genes and environmental factors. Much rarer are the genetic epilepsies that are due to single-gene mutations or defined structural chromosomal aberrations, such as microdeletions. The discovery of several of the genes underlying these rare genetic epilepsies has already considerably contributed to our understanding of the basic mechanisms epileptogenesis. The progress made in the last 15 years in the genetics of epilepsy is providing new possibilities for diagnosis and therapy. Here, different genetic epilepsies are reviewed as examples, to demonstrate the various pathways that can lead from genes to seizures. PMID:18472482

  5. 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.

  6. Multiplex families with epilepsy

    PubMed Central

    Afawi, Zaid; Oliver, Karen L.; Kivity, Sara; Mazarib, Aziz; Blatt, Ilan; Neufeld, Miriam Y.; Helbig, Katherine L.; Goldberg-Stern, Hadassa; Misk, Adel J.; Straussberg, Rachel; Walid, Simri; Mahajnah, Muhammad; Lerman-Sagie, Tally; Ben-Zeev, Bruria; Kahana, Esther; Masalha, Rafik; Kramer, Uri; Ekstein, Dana; Shorer, Zamir; Wallace, Robyn H.; Mangelsdorf, Marie; MacPherson, James N.; Carvill, Gemma L.; Mefford, Heather C.; Jackson, Graeme D.; Scheffer, Ingrid E.; Bahlo, Melanie; Gecz, Jozef; Heron, Sarah E.; Corbett, Mark; Mulley, John C.; Dibbens, Leanne M.; Korczyn, Amos D.

    2016-01-01

    Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. PMID:26802095

  7. Advances in epilepsy surgery

    PubMed Central

    Nowell, Mark; Miserocchi, Anna; McEvoy, Andrew W; Duncan, John S

    2014-01-01

    This review summarises exciting recent and forthcoming advances that will impact on the surgical management of epilepsy in the near future. This does not cover the current accepted diagnostic methodologies or surgical treatments that are routinely practiced today. The content of this review was derived from a PubMed literature search, using the key words ‘Epilepsy Surgery’, ‘Neuromodulation’, ‘Neuroablation’, ‘Advances’, between 2010 and November 2013. PMID:24719180

  8. GEM THERAPY AND EPILEPSY

    PubMed Central

    Murthy, S.R.N.; Shenoy, Raghuram

    1990-01-01

    The authors present in this paper the status of treatment and cause of epilepsy. They propose further research to be undertaken to document the data and a study of human magnetic aura followed by blood spectral studies. They have suggested that based upon these studies it should be possible to determine the cause of epilepsy and its treatment by the physical application of suitable precious and semi-previous stones followed by administration of Ayurvedic formulation. PMID:22557696

  9. 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

  10. Levetiracetam in the treatment of epilepsy

    PubMed Central

    Abou-Khalil, Bassel

    2008-01-01

    Epilepsy is a common chronic disorder that requires long-term antiepileptic drug therapy. Approximately one half of patients fail the initial antiepileptic drug and about 35% are refractory to medical therapy, highlighting the continued need for more effective and better tolerated drugs. Levetiracetam is an antiepileptic drug marketed since 2000. Its novel mechanism of action is modulation of synaptic neurotransmitter release through binding to the synaptic vesicle protein SV2A in the brain. Its pharmacokinetic advantages include rapid and almost complete absorption, minimal insignificant binding to plasma protein, absence of enzyme induction, absence of interactions with other drugs, and partial metabolism outside the liver. The availability of an intravenous preparation is yet another advantage. It has been demonstrated effective as adjunctive therapy for refractory partial-onset seizures, primary generalized tonic-clonic seizures, and myoclonic seizures of juvenile myoclonic epilepsy. In addition, it was found equivalent to controlled release carbamazepine as first-line therapy for partial-onset seizures, both in efficacy and tolerability. Its main adverse effects in randomized adjunctive trials in adults have been somnolence, asthenia, infection, and dizziness. In children, the behavioral adverse effects of hostility and nervousness were also noted. Levetiracetam is an important addition to the treatment of epilepsy. PMID:18830435

  11. 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.

  12. Vitamin D3 for the Treatment of Epilepsy: Basic Mechanisms, Animal Models, and Clinical Trials

    PubMed Central

    Pendo, Kevin; DeGiorgio, Christopher M.

    2016-01-01

    There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D3 is actively under investigation as a potential intervention for epilepsy. Vitamin D3 is fat-soluble steroid, which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D3 may reduce seizures, and animal data support the efficacy of Vitamin D3 in rat and mouse models of epilepsy. Very little clinical data exist to support the treatment of human epilepsy with Vitamin D3, but positive findings from preliminary clinical trials warrant larger Phase I and II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D3 as a treatment for human epilepsy. PMID:28008324

  13. Treatment of typical absence seizures and related epileptic syndromes.

    PubMed

    Panayiotopoulos, C P

    2001-01-01

    Typical absences are brief (seconds) generalised seizures of sudden onset and termination. They have 2 essential components: clinically, the impairment of consciousness (absence) and, generalised 3 to 4Hz spike/polyspike and slow wave discharges on electroencephalogram (EEG). They differ fundamentally from other seizures and are pharmacologically unique. Their clinical and EEG manifestations are syndrome-related. Impairment of consciousness may be severe, moderate, mild or inconspicuous. This is often associated with motor manifestations, automatisms and autonomic disturbances. Clonic, tonic and atonic components alone or in combination are motor symptoms; myoclonia, mainly of facial muscles, is the most common. The ictal EEG discharge may be consistently brief (2 to 5 seconds) or long (15 to 30 seconds), continuous or fragmented, with single or multiple spikes associated with the slow wave. The intradischarge frequency may be constant or may vary (2.5 to 5Hz). Typical absences are easily precipitated by hyperventilation in about 90% of untreated patients. They are usually spontaneous, but can be triggered by photic, pattern, video games stimuli, and mental or emotional factors. Typical absences usually start in childhood or adolescence. They occur in around 10 to 15% of adults with epilepsies, often combined with other generalised seizures. They may remit with age or be lifelong. Syndromic diagnosis is important for treatment strategies and prognosis. Absences may be severe and the only seizure type, as in childhood absence epilepsy. They may predominate in other syndromes or be mild and nonpredominant in syndromes such as juvenile myoclonic epilepsy where myoclonic jerks and generalised tonic clonic seizures are the main concern. Typical absence status epilepticus occurs in about 30% of patients and is more common in certain syndromes, e.g. idiopathic generalised epilepsy with perioral myoclonia or phantom absences. Typical absence seizures are often easy to

  14. Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats.

    PubMed

    Warheit, D B; Boatman, R; Brown, S C

    2015-12-01

    Six different commercial forms and sizes of titanium dioxide particles were tested in separate developmental toxicity assays. The three pigment-grade (pg) or 3 ultrafine (uf)/nanoscale (anatase and/or rutile) titanium dioxide (TiO2) particle-types were evaluated for potential maternal and developmental toxicity in pregnant rats by two different laboratories. All studies were conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). In addition, all test materials were robustly characterized. The BET surface areas of the pg and uf samples ranged from 7 to 17 m(2)/g and 50-82 m(2)/g respectively (see Table 1). The test substances were formulated in sterile water. In all of the studies, the formulations were administered by oral gavage to time-mated rats daily beginning around the time of implantation and continuing until the day prior to expected parturition. In 3 of the studies (uf-1, uf-3, & pg-1), the formulations were administered to Crl:CD(SD) rats beginning on gestation day (GD) 6 through GD 20. In 3 additional studies (uf-2, and pg-2, pg-3 TiO2 particles), the formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition (GD 21 for Crl:CD(SD) rats and GD 20 for Wistar rats). The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal

  15. 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...

  16. The absence of Mth1 inactivation and DNA polymerase kappa overexpression in rat mammary carcinomas with frequent A:T to C:G transversions.

    PubMed

    Okochi, Eriko; Ichimura, Shizue; Sugimura, Takashi; Ushijima, Toshikazu

    2002-05-01

    Single nucleotide instability (SNI), an increase in spontaneous point mutation rates (MRs) without involvement of microsatellite instability, is present in rat mammary carcinoma cell lines and human breast cancer cell lines. A:T to C:G transversions, which are generally rare, were frequently observed in two rat mammary carcinoma cell lines and in their primary carcinomas, and were considered to be related to the molecular mechanism of SNI. In this study, two known molecular mechanisms that cause increases of A:T to C:G transversions, inactivation of the MutT mammalian homologue (Mth1) gene and overexpression of the DNA polymerase k (Pol k) gene, were analyzed in two rat mammary carcinoma cell lines and 11 rat primary carcinomas. PCR-SSCP analysis revealed no mutations in the entire Mth1 coding region. Quantitative real-time RT-PCR analysis showed that Mth1 mRNA expression was slightly, but significantly, increased in the primary carcinomas (P = 0.001 using GAPDH for normalization, and P = 0.002 using histone H4, t-test), contrary to our expectation, and was decreased to 1 / 2 in the cell lines. The expression of Pol k, which is known to be error-prone with frequent A:T to C:G transversions, was rather decreased in the cell lines and primary carcinomas. Inactivation of Mth1 and overexpression of Pol k were unlikely to have caused SNI in the two rat mammary carcinoma cell lines with a high frequency of A:T to C:G transversions, and searching for other unknown molecular mechanisms is important.

  17. Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

    PubMed

    Karimzadeh, Fariba; Soleimani, Mansoureh; Mehdizadeh, Mehdi; Jafarian, Maryam; Mohamadpour, Maliheh; Kazemi, Hadi; Joghataei, Mohammad-Taghi; Gorji, Ali

    2013-12-01

    Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.

  18. Perirhinal cortex and temporal lobe epilepsy.

    PubMed

    Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

    2013-08-29

    The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

  19. Perirhinal cortex and temporal lobe epilepsy

    PubMed Central

    Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

    2013-01-01

    The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

  20. Epilepsy and the Sensory Systems

    PubMed Central

    2016-01-01

    The relations of epilepsy and the sensory systems are bidirectional. Epilepsy may act on sensory systems by producing sensory seizure symptoms, by altering sensory performance, and by epilepsy treatment causing sensory side effects. Sensory system activity may have an important role in both generation and inhibition of seizures. PMID:27857611

  1. 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.

  2. 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.

  3. Epidemiology of epilepsy.

    PubMed

    Abramovici, S; Bagić, A

    2016-01-01

    Modern epidemiology of epilepsy maximizes the benefits of advanced diagnostic methods and sophisticated techniques for case ascertainment in order to increase the diagnostic accuracy and representativeness of the cases and cohorts studied, resulting in better comparability of similarly performed studies. Overall, these advanced epidemiologic methods are expected to yield a better understanding of diverse risk factors, high-risk populations, seizure triggers, multiple and poorly understood causes of epilepsy, including the increasing and complex role of genetics, and establish the natural course of treated and untreated epilepsy and syndromes - all of which form the foundation of an attempt to prevent epileptogenesis as the primary prophylaxis of epilepsy. Although data collection continues to improve, epidemiologists still need to overcome definition and coding variability, insufficient documentation, as well as the interplay of socioeconomic factors and stigma. As most of the 65-70 million people with epilepsy live outside of resource-rich countries, extensive underdiagnosis, misdiagnosis, and undertreatment are likely. Epidemiology will continue to provide the necessary information to the medical community, public, and regulators as the foundation for improved health policies, targeted education, and advanced measures of prevention and prognostication of the most common severe brain disorder.

  4. 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.

  5. 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

  6. Neuropeptide Y and Epilepsy

    PubMed Central

    Colmers, William F.; El Bahh, Bouchaïb

    2003-01-01

    It is a central tenet of the epilepsy field that seizures result from the imbalance of excitation over inhibition 1. The bulk of excitation is mediated by the neurotransmitter glutamate, whereas inhibition results mainly from the actions of γ-aminobutyric acid (GABA). In the neocortex and hippocampus, the intrinsic sources of GABA are the interneurons, which lately have come under intense scrutiny. It has become clear that a large number of distinct types of interneurons can be differentiated in part by the array of neuropeptides they coexpress (cf. 2). Evidence is emerging that the neuropeptide complement of interneurons plays important roles in the way that interneurons regulate excitability. Here we discuss what is known about the relation of one well-characterized neuropeptide, neuropeptide Y (NPY), and epilepsy in experimental animals and humans, and suggest possible roles for the receptors as targets for the control of excessive excitation in epilepsy. PMID:15309085

  7. [Antidepressants in epilepsy].

    PubMed

    Castaño-Monsalve, Beatriz

    2013-08-01

    Depression is a common condition in patients with epilepsy that entails a deterioration of the quality of life of this population and that, therefore, requires appropriate treatment. The potential risk of antidepressants in relation to the seizure threshold is overestimated by many professionals, and this has an influence when it comes to making the decision to treat them. It sometimes means that the patients do not receive antidepressant drugs. In this regard, the aim of this review is to present the current state of the art in terms of the safety of antidepressants in patients with epilepsy. A search of the medical literature was conducted and, following its analysis, the most significant results are presented. Current information indicates that most antidepressants are safe for epileptic patients at therapeutic doses and that the risk of seizures occurs mainly in cases of overdose. Preferred drugs for treating depression in epilepsy are serotonin reuptake inhibitors. Bupropion and tricyclic antidepressants must be avoided.

  8. Medical Marijuana for Epilepsy?

    PubMed Central

    Kolikonda, Murali K.; Srinivasan, Kavitha; Enja, Manasa; Sagi, Vishwanath

    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

  9. Neuroimaging of epilepsy

    PubMed Central

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

    2017-01-01

    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

  10. Computer modeling of Epilepsy

    PubMed Central

    Lytton, William W.

    2009-01-01

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

  11. 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

  12. Examining perceived stigma of children with newly-diagnosed epilepsy and their caregivers over a two-year period.

    PubMed

    Rood, Jennifer E; Schultz, Janet R; Rausch, Joseph R; Modi, Avani C

    2014-10-01

    The purpose of this study was to examine the following: 1) the course of perceived epilepsy-related stigma among children newly diagnosed with epilepsy (n=39) and their caregivers (n=97) over a two-year period, 2) the influence of seizure absence/presence on children and caregivers' perception of epilepsy-related stigma, and 3) the congruence of child and caregiver perception of child epilepsy-related stigma. Participants completed a measure of perceived epilepsy-related stigma at three time points, and seizure status was collected at the final time point. Results indicated that both caregivers (t(1,76)=-2.57, p<.01) and children with epilepsy (t(1,29)=-3.37, p<.01) reported decreasing epilepsy-related stigma from diagnosis to two years postdiagnosis. No significant differences were found in caregiver and child reports of perceived stigma for children experiencing seizures compared with children who have been seizure-free for the past year. Results revealed poor caregiver-child agreement of perceived epilepsy-related stigma at all three time points. These data suggest that while children with epilepsy initially perceive epilepsy-related stigma at diagnosis, their perception of stigma decreases over time. Having a better understanding of the course of epilepsy-related stigma provides clinicians with information regarding critical times to support families with stigma reduction interventions.

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

    PubMed

    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

    2013-12-01

    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 cortico-thalamic 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.

  14. 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

  15. Epilepsy in dental practice.

    PubMed

    Fitzpatrick, J J; McArdle, N S; Wilson, M H; Stassen, L F A

    2008-01-01

    Epilepsy is a neurological condition characterised by seizure activity. It has an approximate incidence of 1%. General dental practitioners will encounter these patients in practice. This article discusses the types of epilepsy, the medical management and considerations in dental management of epileptic patients. General recommendations are made, based on current evidence, with respect to prescribing of medications. The management of an epileptic seizure is discussed. Status epilepticus is a rare but serious complication of epileptic seizures. An easy-to-follow algorithm is provided to assist the practitioner in managing seizures.

  16. Comparison of numbers of interneurons in three thalamic nuclei of normal and epileptic rats.

    PubMed

    Cavdar, Safiye; Bay, Hüsniye Hacioğlu; Yildiz, Sercan D; Akakin, Dilek; Sirvanci, Serap; Onat, Filiz

    2014-06-01

    The inhibitory sources in the thalamic nuclei are local interneurons and neurons of the thalamic reticular nucleus. Studies of models of absence epilepsy have shown that the seizures are associated with an excess of inhibitory neurotransmission in the thalamus. In the present study, we used light-microscopic gamma-aminobutyric acid (GABA) immunocytochemistry to quantify the interneurons in the lateral geniculate (LGN), ventral posteromedial (VPM), and ventral posterolateral (VPL) thalamic nuclei, and compared the values from normal Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS). We found that in both Wistar rats and GAERS, the proportion of interneurons was significantly higher in the LGN than in the VPM and VPL. In the LGN of Wistar rats, 16.4% of the neurons were interneurons and in the GAERS, the value was 15.1%. In the VPM, the proportion of interneurons was 4.2% in Wistar and 14.9% in GAERS; in the VPL the values were 3.7% for Wistar and 11.1% for the GAERS. There was no significant difference between Wistar rats and the GAERS regarding the counts of interneurons in the LGN, whereas the VPM and VPL showed significantly higher counts in GAERS. Comparison of the mean areas of both relay cells and interneuronal profiles showed no significant differences between Wistar rats and GAERS. These findings show that in the VPL and the VPM there are relatively more GABAergic interneurons in GAERS than in Wistar rats. This may represent a compensatory response of the thalamocortical circuitry to the absence seizures or may be related to the production of absence seizures.

  17. Circadian rhythms of PERIOD1 expression in the dorsomedial hypothalamic nucleus in the absence of entrained food-anticipatory activity rhythms in rats.

    PubMed

    Verwey, Michael; Lam, Germain Y M; Amir, Shimon

    2009-06-01

    When food availability is restricted to a single time of day, circadian rhythms of behavior and physiology in rodents shift to anticipate the predictable time of food arrival. It has been hypothesized that certain food-anticipatory rhythms are linked to the induction and entrainment of rhythms in clock gene expression in the dorsomedial hypothalamic nucleus (DMH), a putative food-entrained circadian oscillator. To study this concept further, we made food availability unpredictable by presenting the meal at a random time each day (variable restricted feeding, VRF), either during the day, night or throughout the 24-h cycle. Wheel running activity and the expression of the clock protein, Period1 (PER1), in the DMH and the suprachiasmatic nucleus (SCN) were assessed. Rats exhibited increased levels of activity during the portion of the day when food was randomly presented but, as expected, failed to entrain anticipatory wheel running activity to a single time of day. PER1 expression in the SCN was unchanged by VRF schedules. In the DMH, PER1 expression became rhythmic, peaking at opposite times of day in rats fed only during the day or during the night. In rats fed randomly throughout the entire 24-h cycle, PER1 expression in the DMH remained arrhythmic, but was elevated. These results demonstrate that VRF schedules confined to the day or night can induce circadian rhythms of clock gene expression in the DMH. Such feeding schedules cannot entrain behavioral rhythms, thereby showing that food-entrainment of behavior and circadian rhythms of clock gene expression in the DMH are dissociable.

  18. Expression of sodium channel α subunits 1.1, 1.2 and 1.6 in rat hippocampus after kainic acid-induced epilepsy.

    PubMed

    Qiao, Xin; Werkman, Taco R; Gorter, Jan A; Wadman, Wytse J; van Vliet, Erwin A

    2013-09-01

    Voltage-gated Na(+) channels control neuronal excitability and are the primary target for the majority of anti-epileptic drugs. This study investigates the (sub)cellular expression patterns of three important brain-associated Na(+) channel α subunits: NaV1.1, NaV1.2 and NaV1.6 during epileptogenesis (induced by kainic acid) using time points that cover the period from induction to the chronic phase of epilepsy. NaV1.1 immunoreactivity was persistently reduced at 1 day, 3 weeks and 2 months after SE in CA1 and CA3. About 50% of the NaV1.1-positive interneurons was lost at one day after SE in all regions investigated. In the hilus a similar reduction in NeuN-positive neurons was found, while in the CA1 and CA3 region the loss in NeuN-positive neurons only reached 15% in the chronic phase of epilepsy. This implies a stronger shift in the balance between excitation and inhibition toward excitation in the CA1 and CA3 region than in the hilus. NaV1.2 immunoreactivity in the inner molecular layer of the dentate gyrus was lower than control at 1 day after SE. It increased at 3 weeks and 2 months after SE in the inner molecular layer and overlapped with sprouted mossy fibers. NaV1.6 immunoreactivity in the dendritic region of CA1 and CA3 was persistently reduced at all time-points during epileptogenesis. Some astrocytes expressed NaV1.1 and NaV1.6 at 3 weeks after SE. Expression data alone are not sufficient to explain changes in network stability, or infer causality in epileptogenesis. These results demonstrate that hippocampal sub-regional expression of NaV1.1, NaV1.2 and NaV1.6 Na(+) channel α subunits is altered during epileptogenesis in a time and location specific way. This implies that understanding epileptogenesis has to take into account several distinct and type-specific changes in sodium channel expression.

  19. Diallyl sulfide induces the expression of estrogen metabolizing genes in the presence and/or absence of diethylstilbestrol in the breast of female ACI rats.

    PubMed

    Green, Mario; Newell, Oneil; Aboyade-Cole, Ayoola; Darling-Reed, Selina; Thomas, Ronald D

    2007-01-10

    Diethylstilbestrol (DES) induces mammary tumors in female ACI rats and is associated with an increased risk of developing breast cancer in humans. Diallyl sulfide (DAS) has been shown to prevent cancer in animals. Previously, we have shown that DAS inhibits the production of DES induced DNA adducts when given prior to DES. We hypothesize that DAS alters the expression of genes responsible for DES metabolism. To test this hypothesis, four groups of 10 female ACI rats were treated daily for four days as follows: (1) corn oil, (2) 50mg/kg DES, (3) 50mg/kg DAS, and (4) 50mg/kg DAS+50mg/kg DES. RNA was isolated from breast tissue and mRNA levels of CYP1A1, CYP1B1, glutathione-S-transferase (GST) and superoxide dismutase (SOD) were analyzed by real-time PCR. DES, DAS, and DES/DAS treatments increased the expression of CYP1A1 by 2.1-, 4.7-, and 12.7-fold, respectively. Similar results were seen for CYP1B1. DES decreased the expression of GST by 23%, whereas DAS and DAS/DES treatments increased the expression of GST by 12- and 16.7-fold, respectively. Similar results were seen with SOD. These results suggests that DAS may prevent the formation of DES induced DNA damage by altering the expression of DES metabolizing genes.

  20. 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.

  1. Theories of Impaired Consciousness in Epilepsy

    PubMed Central

    Yu, Lissa; Blumenfeld, Hal

    2015-01-01

    Although the precise mechanisms for control of consciousness are not fully understood, emerging data show that conscious information processing depends on the activation of certain networks in the brain and that the impairment of consciousness is related to abnormal activity in these systems. Epilepsy can lead to transient impairment of consciousness, providing a window into the mechanisms necessary for normal consciousness. Thus, despite differences in behavioral manifestations, cause, and electrophysiology, generalized tonic–clonic, absence, and partial seizures engage similar anatomical structures and pathways. We review prior concepts of impaired consciousness in epilepsy, focusing especially on temporal lobe complex partial seizures, which are a common and debilitating form of epileptic unconsciousness. We discuss a “network inhibition hypothesis” in which focal temporal lobe seizure activity disrupts normal cortical–subcortical interactions, leading to depressed neocortical function and impaired consciousness. This review of the major prior theories of impaired consciousness in epilepsy allows us to put more recent data into context and to reach a better understanding of the mechanisms important for normal consciousness. PMID:19351355

  2. Brain maturation and epilepsy.

    PubMed

    Dulac, Olivier; Milh, Mathieu; Holmes, Gregory L

    2013-01-01

    At full term, both glutamate and gamma-amino-butyric acid (GABA) are excitatory; cortical synapses are beginning to appear, there is little myelin in the cerebral hemispheres, and long tracts hardly start to develop. Neonatal myoclonic encephalopathy can result from premature activation of N-methyl-D-aspartate (NMDA) transmission. Benign neonatal seizures and migrating partial seizures in infancy could involve excessive or premature excitability of deep cortical layers. Benign rolandic epilepsy and continuous spike waves in slow sleep are consistent with an excess of both excitatory and inhibitory cortical synapses. West and Lennox-Gastaut syndromes express age-related diffuse cortical hyperexcitability, the pattern depending on the age of occurrence; synchronization of spikes is becoming possible with maturation of the myelin. Idiopathic generalized epilepsy is itself modulated by maturation that causes frontal hyperexcitability generating myoclonic-astatic seizures, between the ages of infantile and juvenile myoclonic epilepsies. Physiological delay of hippocampo-neocortical pathways maturation could account for the delayed occurrence of mesial temporal epilepsy following infantile damage, whereas premature maturation could contribute to fronto-temporal damage characteristic of fever-induced epileptic encephalopathy in school-age children, a dramatic school-age epileptic encephalopathy.

  3. In utero methanesulfonyl fluoride differentially affects learning and maze performance in the absence of long-lasting cholinergic changes in the adult rat

    PubMed Central

    Carcoba, Luis M .; Santiago, Miguel; Moss, Donald E.; Cabeza, Rafael

    2008-01-01

    There is increasing evidence that acetylcholinesterase (AChE) may have various specific developmental roles in brain development. Nevertheless, specific effects of AChE inhibition during early brain development have not been adequately described. Therefore, methanesulfonyl fluoride (MSF), an irreversible AChE inhibitor that shows high selectivity for the CNS was used to produce AChE inhibition in utero to study subsequent adult behaviors, sleep, and cholinergic markers. Rats exposed to MSF in utero showed a deficit in spatial learning tasks using appetitive motivation but, surprisingly, they performed equally well or better than controls when aversive motivation was used. One hypothesis was that MSF treatment in utero affected the response to stress. Tests of anxiety however showed no differences in basal levels of anxiety. Studies of sleep behavior, however, indicated a higher level of REM sleep which is only seen during the light phase of male rats exposed to MSF in utero as compared to controls. No differences in cholinergic markers in the brains of adults were found except that females exposed to MSF in utero had a higher level of ChAT activity in the synaptosomal fraction of the hippocampus. Even so, whether cholinergic alterations accompany the in utero MSF exposure remains to be determined. The failure to find widespread changes in cholinergic markers in the adult brains suggests changes in behaviors should be further investigated by testing the participation of postsynaptic mechanisms, measuring of cholinergic markers during earlier development periods and the possible participation of other neurotransmitter systems to clearly reveal the role of the cholinergic system following in utero MSF exposure. PMID:17920111

  4. 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

  5. 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 ...

  6. Future directions in the neuropsychology of epilepsy.

    PubMed

    McDonald, Carrie R; Taylor, Joanne; Hamberger, Marla; Helmstaedter, Christoph; Hermann, Bruce P; Schefft, Bruce

    2011-09-01

    Two important themes for future clinical research in the neuropsychology of epilepsy are proposed: (1) the neurobiological abnormalities that underlie neuropsychological impairment in people with epilepsy, and (2) neuropsychological status of persons with new-onset epilepsy.

  7. 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

  8. 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

  9. 12-tetradecanoyl-phorbol-13-acetate (PMA) produces injury to isolated rat lungs in the presence and absence of perfused neutrophils

    SciTech Connect

    Carpenter, L.J.; Roth, R.A.

    1986-03-01

    PMA produced injury to isolated, perfused rat lungs when eutrophils were added to or omitted from the buffer/albumin perfusion medium. When a high dose of PMA (57 ng/ml) was added to medium devoid of added neutrophils, perfusion pressure and lung weight increased. Together, superoxide dismutase (500 U/ml) and catalase (400 U/ml) had no effect on the increases in lung weight or perfusion pressure. However, papaverine (0.5 mM) prevented both the increase in perfusion pressure and fluid accumulation. When a concentration of PMA (14 ng/ml) that did not by itself cause lungs to accumulate fluid was added to perfusion medium containing neutrophils (1 x 10/sup 8/), perfusion pressures increased and lungs accumulated fluid. This concentration of PMA stimulated neutrophils (1 x 10/sup 8/) to release superoxide. Addition of superoxide dismutase (500 U/ml) and catalase (400 U/ml) to this medium prevented the increase in lung weight, but not the increase in perfusion pressure. Papaverine (0.5 mM) attenuated the increase in perfusion pressure and prevented fluid accumulation in these lungs. In summary, high concentrations of PMA produce lung injury which is independent of oxygen radicals; at lower concentrations it produces injury which is neutrophil-dependent and mediated by oxygen radicals.

  10. Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats.

    PubMed

    Leite, Aline de Lima; Santiago, Joel Ferreira; Levy, Flavia Mauad; Maria, Andrea Gutierrez; Fernandes, Mileni da Silva; Salvadori, Daisy Maria Favero; Ribeiro, Daniel Araki; Buzalaf, Marilia Afonso Rabelo

    2007-05-01

    Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

  11. Classification of seizures and epilepsy.

    PubMed

    Riviello, James J

    2003-07-01

    The management of seizures and epilepsy begins with forming a differential diagnosis, making the diagnosis, and then classifying seizure type and epileptic syndrome. Classification guides treatment, including ancillary testing, management, prognosis, and if needed, selection of the appropriate antiepileptic drug (AED). Many AEDs are available, and certain seizure types or epilepsy syndromes respond to specific AEDs. The identification of the genetics, molecular basis, and pathophysiologic mechanisms of epilepsy has resulted from classification of specific epileptic syndromes. The classification system used by the International League Against Epilepsy is periodically revised. The proposed revision changes the classification emphasis from the anatomic origin of seizures (focal vs generalized) to seizure semiology (ie, the signs or clinical manifestations). Modified systems have been developed for specific circumstances (eg, neonatal seizures, infantile seizures, status epilepticus, and epilepsy surgery). This article reviews seizure and epilepsy classification, emphasizing new data.

  12. Molecular biology of epilepsy genes.

    PubMed

    Williams, Charles A; Battaglia, Agatino

    2013-06-01

    Multifactorial inheritance is the most important model accounting for the genetic behavior of the common epilepsies. Important to this model is the concept that many cumulative or synergistic risk genes ultimately lead to a threshold effect. Sophisticated molecular testing indicates that the common epilepsies are very polygenic without evidence of any single gene having even a mild-to-modest risk effect. However, enrichment of copy number variants in cohorts of individuals with epilepsy indicates that certain structural changes in the genome can confer significant risk for epilepsy. The mechanisms whereby copy number variants confer this effect are not yet known. The study of epilepsy due to single gene defects however has helped clarify certain seizure mechanisms. For example, discoveries using animal models of SCN1A or ARX mutations implicate a predominant role for interneurons due to disturbed GABAergic function. It is hoped that future genetic and neurobiological studies will provide better insight into how multiple genes contribute to the common epilepsies.

  13. 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

  14. Role of Mas receptor antagonist (A779) on pressure diuresis and natriuresis and renal blood flow in the absence of angiotensin II receptors type 1 and 2 in female and male rats.

    PubMed

    Mansoori, A; Oryan, S; Nematbakhsh, M

    2014-10-01

    Sexual differences in blood pressure are associated with angiotensin 1-7 (Ang1-7) and its receptor and enzyme function targeting. Blockade of angiotensin II (AngII) receptors type 1 and 2 (AT1R and AT2R) inhibits some actions of Ang1-7. We described the role of Ang1-7 receptor (MasR) antagonist (A779) on kidney hemodynamics when AT1R and AT2R are blocked with losartan and PD123319. In anaesthetized male and female rats after blockade of both AT1R and AT2R, the renal perfusion pressure (RPP) was controlled in two levels of 80 and 100 mmHg via an adjustable clamp placed around the aorta above the level of the renal arteries. Then, the effects of saline vehicle and MasR blocker (A779) were tested on pressure natriuresis and diuresis, renal blood flow (RBF), and renal vascular resistance (RVR). In the absence of AT1R and AT2R; RVR, RBF/wet kidney tissue weight, and serum level of renin did not alter in both genders either MasR was blocked or not. However, urine flow rate (UF) and sodium excretion (UNaV) increased significantly at the pressure level of 100 mmHg in the presence of MasR in male (P<0.05) but not in female rats. When AT1R and AT2R were blocked, the impact of MasR is gender-related in pressure natriuresis and diuresis, and pressure natriuresis and diuresis in male rats (not female) increases in the presence of MasR.

  15. Parkinson's Disease and Cryptogenic Epilepsy.

    PubMed

    Son, Andre Y; Biagioni, Milton C; Kaminski, Dorian; Gurevich, Alec; Stone, Britt; Di Rocco, Alessandro

    2016-01-01

    Epilepsy is an uncommon comorbidity of Parkinson's disease (PD) and has been considered not directly associated with PD. We present five patients (3 men and 2 women; ages 49-85) who had concomitant PD and cryptogenic epilepsy. Although rare, epilepsy can coexist with PD and their coexistence may influence the progression of PD. While this may be a chance association, an evolving understanding of the neurophysiological basis of either disease may suggest a mechanistic association.

  16. Parkinson's Disease and Cryptogenic Epilepsy

    PubMed Central

    Kaminski, Dorian; Gurevich, Alec; Stone, Britt; Di Rocco, Alessandro

    2016-01-01

    Epilepsy is an uncommon comorbidity of Parkinson's disease (PD) and has been considered not directly associated with PD. We present five patients (3 men and 2 women; ages 49–85) who had concomitant PD and cryptogenic epilepsy. Although rare, epilepsy can coexist with PD and their coexistence may influence the progression of PD. While this may be a chance association, an evolving understanding of the neurophysiological basis of either disease may suggest a mechanistic association. PMID:27688919

  17. [Myoclonus and epilepsies in children].

    PubMed

    Fejerman, N

    1991-01-01

    The possible associations of myoclonic phenomena, progressive or non progressive encephalopathies and epileptic phenomena are reviewed with special emphasis on childhood. This leads to the following five groups of conditions: (1) myoclonus without encephalopathy and without epilepsy; (2) encephalopathies with non-epileptic myoclonus; (3) progressive encephalopathies with myoclonic seizures or epileptic syndromes (Progressive myoclonus epilepsies); (4) epileptic encephalopathies with myoclonic seizures; (5) myoclonic epilepsies. In the first group, which also includes physiological myoclonus, a more thorough description of "benign sleep myoclonus of newborn" and "benign myoclonus of early infancy" is given. Characteristic of group 2 are "Kinsbourne syndrome" and certain types of "Hyperekplexia" which pose interesting differential diagnosis problems with stimulus-sensitive epilepsies. In group 3, the concept of progressive encephalopathies is stressed, meaning that "Progressive Myoclonus Epilepsies" are always in fact progressive encephalopathies presenting with myoclonic types of seizures or epileptic syndromes among other neurologic and psychologic signs and symptoms. Major and rare causes are reviewed. The term major is applied to typical features or to frequency, whereas rare causes include not only those what are rarely seen, but also some myoclonic variants of diseases which usually have different symptoms. The fourth group refers to severe epilepsies, mainly in infancy and childhood, which lead to mental retardation irrespective of their cause. The assumption is that diffuse and persistent epileptic activity may interfere with normal development of the higher cerebral functions. "West syndrome" and "Lennox-Gastaut syndrome" are the more representative examples and may present with myoclonic type of seizures, but they are not dealt with in detail here. Group 5 comprises true myoclonic epilepsies, differentiating syndromes recognized as idiopathic, such as

  18. Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes

    PubMed Central

    Talbott, Jason F.; Loy, David N.; Liu, Ying; Qiu, Mengsheng S.; Bunge, Mary Bartlett; Rao, Mahendra S.; Whittemore, Scott R.

    2010-01-01

    Chronic demyelination is a pathophysiologic component of compressive spinal cord injury (SCI) and a characteristic finding in demyelinating diseases including multiple sclerosis (MS). A better characterization of endogenous cells responsible for successful remyelination is essential for designing therapeutic strategies aimed at restoring functional myelin. The present study examined the spatiotemporal response of endogenous oligodendrocyte precursor cells (OPCs) following ethidium bromide (EB)-induced demyelination of the adult rat spinal cord. Beginning at 2 days post-EB injection (dpi), a robust mobilization of highly proliferative NG2+ cells within the lesion was observed, none of which expressed the oligodendrocyte lineage-associated transcription factor Nkx2.2. At 7 dpi, a significant up-regulation of Nkx2.2 by OPCs within the lesion was observed, 90% of which coexpressed NG2 and virtually all of which coexpressed the bHLH transcription factor Olig2. Despite successful recruitment of Nkx2.2+/Olig2+ OPCs within the lesion, demyelinated axons were not remyelinated by these OPCs in regions lacking astrocytes. Rather, Schwann cell remyelination predominated throughout the central core of the lesion, particularly around blood vessels. Oligodendrocyte remyelination was observed in the astrogliotic perimeter, suggesting a necessary role for astrocytes in oligodendrocyte maturation. In addition, reexpression of the radial glial antigen, RC-1, by reactive astrocytes and ependymal cells was observed following injury. However, these cells did not express the neural stem cell (NSC)-associated transcription factors Sox1 or Sox2, suggesting that the endogenous response is primarily mediated by glial progenitors. In vivo electrophysiology demonstrated a limited and unsustained functional recovery concurrent with endogenous remyelination following EB-induced lesions. PMID:15698615

  19. Absence seizures with myoclonic features in a juvenile Chihuahua dog.

    PubMed

    Poma, Roberto; Ochi, Ayako; Cortez, Miguel A

    2010-06-01

    Long-term video-EEG was recorded for an eight-month-old Chihuahua dog with recurrent episodes of altered behaviour associated with head and nose twitching. Each episode lasted one to two seconds, multiple times per day before treatment. Ictal EEG showed generalised bilaterally synchronous 4 Hz spike-and-wave complexes during the "absence-like" event, along with rhythmically correlated head and nose twitching. We present video documentation of such attacks and discuss their similarities to human epilepsy with myoclonic absences.

  20. 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.

  1. Epilepsy and videogames.

    PubMed

    Bureau, Michelle; Hirsch, Edouard; Vigevano, Federico

    2004-01-01

    Since the first case of videogame (VG) epilepsy was reported in 1981, many cases of seizures triggered by VGs were reported, not only in photosensitive, but also in non-photosensitive children and adolescents with epilepsy. We provide an overview of the literature with overall conclusions and recommendations regarding VG playing. Specific preventive measures concerning the physical characteristics of images included in commercially available VGs (flash rate, choice of colors, patterns, and contrast) can lead in the future to a clear decrease of this problem. In addition to the positive effect of such measures, the collaborative studies performed in France and in the rest of Europe have stressed the importance of a safe distance to the screen of > or = 2 m, and the less provocative role of 100-Hz screens.

  2. [Biofeedback treatment for epilepsy].

    PubMed

    Nagai, Yoko

    2014-05-01

    Pharmacological treatment is the mainstay for the treatment of epilepsy. However concerns regarding long-term side effects of drugs are increasingly voiced. Behavioral treatments including biofeedback, represents an alternative management option for the control of epilepsy. Biofeedback is a non-invasive bio-behavioral procedure through which patients can learn to gain psychophysiological control over seizures. This article will first overview seizure precipitation from a psychological perspective, and then introduce three major biofeedback treatments. Sensory motor rhythm (SMR) and slow cortical potential(SCP) biofeedback uses electroencephalographic parameters and are categorized as neurofeedback. Electrodermal activity (EDA) biofeedback focuses on modulation of peripheral sympathetic tone. The neural mechanisms underlying biofeedback treatment will be discussed in relation to thalamo-cortical regulation(of neural excitability across brain networks).

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

    PubMed Central

    Sivakumar, Siddharth S.; Namath, Amalia G.; Tuxhorn, Ingrid E.; Lewis, Stephen J.

    2016-01-01

    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

  4. Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in infancy and related epilepsies.

    PubMed

    Fujiwara, Tateki

    2006-08-01

    Severe myoclonic epilepsy in infancy (SMEI) manifests very frequent generalized tonic-clonic seizures (GTC), accompanied by myoclonic seizures, absences and partial seizures [Dravet, C., 1978. Les épilepsie grave de l'enfant. Vie Méd. 8, 543-548; Dravet, C., Roger, J., Bureau, M., Dalla Bernardina, B., 1982. Myoclonic epilepsies in childhood. In: Akimoto, H., Kazamatsuri, H., Seino, M., Ward, A. (Eds.), Advances in Epileptology. Raven Press, New York, pp. 135-140; Dravet, C., Bureau, M., Oguni, H., Fukuyama, Y., Cokar, O., 2002. Severe myoclonic epilepsy of infancy (Dravet syndrome). In: Roger, J., Bureau, M., Dravet, C., Genton, P., Tassinari, C.A., Wolf, P. (Eds.), Epileptic Syndromes in Infancy, Childhood and Adolescence, third ed. John Libbey, London, pp. 81-103]. However, there is a group of severe epilepsy that has many characteristics common to SMEI except for myoclonic seizures. We reported this group of epilepsy as intractable childhood epilepsy with GTC (ICEGTC) [Watanabe, M., Fujiwara, T., Yagi, K., Seino, M., Higashi, T., 1989b. Intractable childhood epilepsy with generalized tonic-clonic seizures. J. Jpn. Epil. Soc. 7, 96-105 (in Japanese); Fujiwara, T., Watanabe, M., Takahashi, Y., Higashi, T., Yagi, K., Seino, M., 1992. Long-term course of childhood epilepsy with intractable grand mal seizures. Jpn. J. Psychiatr. Neurol. 46, 297-302]. Recently, mutations of the neuronal voltage-gated sodium channel alphasubunit type 1 gene (SCN1A) have been found in SMEI [Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., De Jonghe, P., 2001, De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68, 327-1332]. Mutations in SCN1A are found in both SMEI and ICEGTC at high rates of 70-81%. The loci of the mutations seen in ICEGTC are quite similar to those found in SMEI, suggesting a genotypic continuity between these entities. The clinical spectrum of epilepsies harboring SCN1A

  5. Tuberous Sclerosis with Epilepsy

    DTIC Science & Technology

    2009-02-01

    50% of individuals with TS have learning difficulties that include autism , attention-deficit hyperactivity disorder (ADHD), behavioral issues...These findings of TS manifest themselves symptomatically as seizures, epilepsy, and learning disabilities including autism , ADHD, behavioral...molecular pathogenesis to rationale for treatment”. J Child Neurol 2005; 20:318 –325. 15) Chandra PS, Salamon N, Huang J, et al. “FDG-PET/MRI

  6. Photoacoustic Imaging of Epilepsy

    DTIC Science & Technology

    2012-04-01

    NUMBER University of Florida Biomedical Sciences Building Gainesville, FL 32611 9. SPONSORING / MONITORING AGENCY NAME(S...however, 80% individuals with medication resistant epilepsy might be cured through surgery if one were able to precisely localize the seizure focus...6–15 (2001). 4. L. A. Kunyansky, “Explicit inversion formulae for the spherical mean radon transform,” Inverse Probl. 23(1), 373–383 (2007). 5. D

  7. Photoacoustic Imaging of Epilepsy

    DTIC Science & Technology

    2014-04-01

    NeuroImage 66 (2013) 240–248( Bertram , 2009) and that current diagnostics methods frequently fall short of identifying such sites. Animal studies...indicate that the neu- rons involved in the epileptic circuitry have enhanced excitability throughout ( Bertram et al., 1998; Fountain et al., 1998; Mangan... Bertram , E.H., 2009. Temporal lobe epilepsy: where do the seizures really begin? Epi- lepsy Behav. 14, 32–37. Bertram , E.H., Zhang, D.X., Mangan, P

  8. Periventricular heterotopia and epilepsy.

    PubMed

    Huttenlocher, P R; Taravath, S; Mojtahedi, S

    1994-01-01

    We report a family with nodular subependymal masses of heterotopic gray matter occurring in six members in four generations. Only female members of the family are affected, and there is a high rate of spontaneous abortion, consistent with X-linked dominant inheritance, and lack of viability in affected males. Both in this family and in sporadic cases of subependymal heterotopias there is a high frequency of convulsive disorders, suggesting that epilepsy may be the major clinical manifestation of this developmental defect.

  9. Quantitative analysis of intermediary metabolism in rat hepatocytes incubated in the presence and absence of ethanol with a substrate mixture including ketoleucine.

    PubMed

    Baranyai, J M; Blum, J J

    1989-02-15

    Hepatocytes isolated from livers of fed rats were incubated with a mixture of glucose (10 mM), ribose (1.0 mM), acetate (1.25 mM), alanine (3.5 mM), glutamate (2.0 mM), aspartate (2.0 mM), 4-methyl-2-oxovaleric acid (ketoleucine) (3.0 mM), and, in paired flasks, 10 mM-ethanol. One substrate was 14C-radiolabelled in any given incubation. Incorporation of 14C into glucose, glycogen, CO2, lactate, alanine, aspartate, glutamate, acetate, urea, lipid glycerol, fatty acids and the 1- and 2,3,4-positions of ketone bodies was measured after 20 and 40 min of incubation under quasi-steady-state conditions. Data were analysed with the aid of a realistic structural metabolic model. In each of the four conditions examined, there were approx. 77 label incorporation measurements and several measurements of changes in metabolite concentrations. The considerable excess of measurements over the 37 independent flux parameters allowed for a stringent test of the model. A satisfactory fit to these data was obtained for each condition. There were large bidirectional fluxes along the gluconeogenic/glycolytic pathways, with net gluconeogenesis. Rates of ureagenesis, oxygen consumption and ketogenesis were high under all four conditions studied. Oxygen utilization was accurately predicted by three of the four models. There was complete equilibration between mitochondrial and cytosolic pools of acetate and of CO2, but for several of the metabolic conditions, two incompletely equilibrated pools of mitochondrial acetyl-CoA and oxaloacetate were required. Ketoleucine was utilized at a rate comparable to that reported by others in perfused liver and entered the mitochondrial pool of acetyl-CoA directly associated with ketone body formation. Ethanol, which was metabolized at rates comparable to those in vivo, caused relatively few changes in overall flux patterns. Several effects related to the increased NADH/NAD+ ratio were observed. Pyruvate dehydrogenase was completely inhibited and the ratio

  10. Epilepsy and chromosomal abnormalities

    PubMed Central

    2010-01-01

    Background Many chromosomal abnormalities are associated with Central Nervous System (CNS) malformations and other neurological alterations, among which seizures and epilepsy. Some of these show a peculiar epileptic and EEG pattern. We describe some epileptic syndromes frequently reported in chromosomal disorders. Methods Detailed clinical assessment, electrophysiological studies, survey of the literature. Results In some of these congenital syndromes the clinical presentation and EEG anomalies seems to be quite typical, in others the manifestations appear aspecific and no strictly linked with the chromosomal imbalance. The onset of seizures is often during the neonatal period of the infancy. Conclusions A better characterization of the electro clinical patterns associated with specific chromosomal aberrations could give us a valuable key in the identification of epilepsy susceptibility of some chromosomal loci, using the new advances in molecular cytogenetics techniques - such as fluorescent in situ hybridization (FISH), subtelomeric analysis and CGH (comparative genomic hybridization) microarray. However further studies are needed to understand the mechanism of epilepsy associated with chromosomal abnormalities. PMID:20438626

  11. 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

  12. Dietary therapies for epilepsy.

    PubMed

    Kossoff, Eric H; Wang, Huei-Shyong

    2013-01-01

    Since their introduction in 1921, high-fat, low-carbohydrate "ketogenic" diets have been used worldwide for refractory childhood epilepsy. Approximately half of the children have at least half their seizures reduced, including 15% who are seizure free. The mechanisms of action of dietary therapies are under active investigation and appear to involve mitochondria. Once perceived as a last resort, modifications to initiation and maintenance, as well as the widespread use of pre-made ketogenic formulas have allowed dietary treatment to be used earlier in the course of epilepsy. For infantile spasms (West syndrome) specifically, the ketogenic diet is successful about 50% of the time as a first-line treatment. New "alternative" diets such as the modified Atkins diet were created in 2003 and can be started more easily and are less restrictive. They may have particular value for countries in Asia. Side effects include constipation, dyslipidemia, growth slowing, acidosis, and kidney stones. Additionally, neurologists are studying ketogenic diets for conditions other than epilepsy, including Alzheimer's disease, autism, and brain tumors.

  13. The use of automated system for EEG analysis and feedback cerebral stimulation to stop epileptiform activity in WAG/Rij rats.

    PubMed

    Blik, V A; Aristov, A V; Chepurnova, N E

    2015-02-01

    Original software program is described, which revealed EEG activity characteristic of the onset of epileptic seizure and turned on electrical stimulation of the nucleus basalis of Meynert in WAG/Rij rats with congenital absence epilepsy. The program reliably detected the onset of seizure and automatically stopped it with a high-frequency train of electrical impulses (100-150 Hz). Thus, a feedback system of deep brain stimulation has been developed to stop early manifestations of absence epileptiform seizures. The study can be a base to develop an implanted apparatus to automatically analyze EEG and stimulate the brain to stop the epileptic seizures.

  14. The extratemporal lobe epilepsies in the epilepsy monitoring unit

    PubMed Central

    Dash, Deepa; Tripathi, Manjari

    2014-01-01

    Extratemporal lobe epilepsies (ETLE) are characterized by the epileptogenic foci outside the temporal lobe. They have a wide spectrum of semiological presentation depending upon the site of origin. They can arise from frontal, parietal, occipital lobes and from hypothalamic hamartoma. We discuss in this review the semiology of different types of ETLE encountered in the epilepsy monitoring unit. PMID:24791090

  15. 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…

  16. New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

    DTIC Science & Technology

    2013-05-01

    epilepsy in parallel with Dr. Stanton’s laboratories. For our surprise, animals obtained from Jackson laboratories, Inc exhibited an increased...resistance to enter status epilepticus in contrast to colonies established at Dr. Stanton’s laboratories based in animals originally provided by Dr...increase the number of animals to continue the imaging studies, specially using the new imaging capabilities. Model of chronic epilepsy in rats: All

  17. Characterization of cortical spreading depression in adult well-nourished and malnourished rats submitted to the association of pilocarpine-induced epilepsy plus streptozotocin-induced hyperglycemia.

    PubMed

    Costa-Cruz, Raquel Raimunda Goldstein; Amâncio-dos-Santos, Angela; Guedes, Rubem Carlos Araújo

    2006-07-03

    Spreading depression was characterized in adult rats rendered epileptic by pilocarpine (350 mg/kg, i.p.) and thereafter made hyperglycemic with (i.p.) 60 mg/kg streptozotocin. Groups treated with only one of the above drugs, as well as control groups treated with their vehicles (saline and citrate buffer, respectively) were also studied. The animals treated with pilocarpine or streptozotocin presented, as a common feature, a reduction in the spreading depression propagation rate. However, they differed by the fact that pilocarpine, in some cases, blocked spreading depression propagation, whereas streptozotocin did not block it at all. In early-malnourished animals, streptozotocin-effects, but not pilocarpine-effects on spreading depression were attenuated. The treatment with both drugs did not potentiate their individual reducing effects on spreading depression propagation, irrespective of the animals' early nutritional status. These results extend previous observations on rats treated with both drugs separately, confirming their impairing action on spreading depression propagation. They also indicate that early malnutrition is more effective in changing the streptozotocin effects on spreading depression, as compared to the pilocarpine-effects. Since such effects were observed at adulthood, they indicate that the early malnutrition-induced cortical changes responsible for the here-described effects are long-lasting.

  18. Aberrant neuronal avalanches in cortical tissue removed from juvenile epilepsy patients.

    PubMed

    Hobbs, Jon P; Smith, Jodi L; Beggs, John M

    2010-12-01

    Some forms of epilepsy may arise as a result of pathologic interactions among neurons. Many forms of collective activity have been identified, including waves, spirals, oscillations, synchrony, and neuronal avalanches. All these emergent activity patterns have been hypothesized to show pathologic signatures associated with epilepsy. Here, the authors used 60-channel multielectrode arrays to record neuronal avalanches in cortical tissue removed from juvenile epilepsy patients. For comparison, they also recorded activity in rat cortical slices. The authors found that some human tissue removed from epilepsy patients exhibited prolonged periods of hyperactivity not seen in rat slices. In addition, they found a positive correlation between the branching parameter, a measure of network gain, and firing rate in human slices during periods of hyperactivity. This relationship was not present in rat slices. The authors suggest that this positive correlation between the branching parameter and the firing rate is part of a positive feedback loop and may contribute to some forms of epilepsy. These results also indicate that neuronal avalanches are abnormally regulated in slices removed from pediatric epilepsy patients.

  19. 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…

  20. Epilepsy and vaccinations: Italian guidelines.

    PubMed

    Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto

    2013-10-01

    Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination.

  1. Agenesis of the Corpus Callosum and Generalized Epilepsy.

    PubMed

    Ilik, Faik; Bilgilisoy, Ugur T

    2015-07-01

    The corpus callosum is the main band of interhemispheric axonal fibers in the human brain. Corpus callosum agenesis has widely varying symptoms, mainly associated with epilepsy, cognitive failure, and different neuropsychiatric disorders. Our case of corpus callosum agenesis includes eyelid myoclonia with absences. In the literature, there is no reported case of this combination. We report this case because it is rare, and relevant for the understanding of interhemispheric communications, based on our electrophysiological findings.

  2. Gelastic epilepsy: Beyond hypothalamic hamartomas.

    PubMed

    Uribe-San-Martin, Reinaldo; Ciampi, Ethel; Lawson-Peralta, Balduin; Acevedo-Gallinato, Keryma; Torrealba-Marchant, Gonzalo; Campos-Puebla, Manuel; Godoy-Fernández, Jaime

    2015-01-01

    Gelastic epilepsy or laughing seizures have been historically related to children with hypothalamic hamartomas. We report three adult patients who had gelastic epilepsy, defined as the presence of seizures with a prominent laugh component, including brain imaging, surface/invasive electroencephalography, positron emission tomography, and medical/surgical outcomes. None of the patients had hamartoma or other hypothalamic lesion. Two patients were classified as having refractory epilepsy (one had biopsy-proven neurocysticercosis and the other one hippocampal sclerosis and temporal cortical dysplasia). The third patient had no lesion on MRI and had complete control with carbamazepine. Both lesional patients underwent resective surgery, one with complete seizure control and the other one with poor outcome. Although hypothalamic hamartomas should always be ruled out in patients with gelastic epilepsy, laughing seizures can also arise from frontal and temporal lobe foci, which can be surgically removed. In addition, we present the first case of gelastic epilepsy due to neurocysticercosis.

  3. The neurosurgical treatment of epilepsy.

    PubMed

    Tatum, W O; Benbadis, S R; Vale, F L

    2000-01-01

    Despite the new advancements in antiepileptic drug development, thousands of people with epilepsy will remain intractable to medication. For a considerable proportion of these people, epilepsy surgery is a consideration for better control of their seizures. Resective surgery is now standard practice for patients with medication-refractory epilepsy. Temporal lobectomy continues to be the most common surgery performed. Once patients fail 2 to 3 optimal trials of antiepileptic medication, further drug therapy offers a minimal number of patients freedom from seizures. In contrast, temporal lobectomy in carefully selected patients may result in seizure-free outcomes in more than 70% to 90% of patients with intractable seizures. As technology and drug availability increases in the new millennium, it is important for the primary care physician to be aware of epilepsy surgery as a means to treat patients with antiepileptic drug-refractory epilepsy. Arch Fam Med. 2000;9:1142-1147

  4. Genetic models of focal epilepsies.

    PubMed

    Boillot, Morgane; Baulac, Stéphanie

    2016-02-15

    Focal epilepsies were for a long time thought to be acquired disorders secondary to cerebral lesions. However, the important role of genetic factors in focal epilepsies is now well established. Several focal epilepsy syndromes are now proven to be monogenic disorders. While earlier genetic studies suggested a strong contribution of ion channel and neurotransmitter receptor genes, later work has revealed alternative pathways, among which the mammalian target of rapamycin (mTOR) signal transduction pathway with DEPDC5. In this article, we provide an update on the mutational spectrum of neuronal nicotinic acetylcholine receptor genes (CHRNA4, CHRNB2, CHRNA2) and KCNT1 causing autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), and of LGI1 in autosomal dominant epilepsy with auditory features (ADEAF). We also emphasize, through a review of the current literature, the contribution of in vitro and in vivo models developed to unveil the pathogenic mechanisms underlying these two epileptic syndromes.

  5. Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggest post-transcriptional regulation in the spontaneously hypertensive rat model of ADHD

    PubMed Central

    Wigestrand, MB; Mineur, YS; Heath, CJ; Fonnum, F; Picciotto, MR; Walaas, SI

    2011-01-01

    The spontaneously hypertensive rat (SHR) is widely used as a model of attention-deficit/hyperactivity disorder (ADHD). Deficits in central nicotinic receptors (nAChRs) have previously been observed in SHRs, which is interesting since epidemiological studies have identified an association between smoking and ADHD symptoms in humans. Here we examine whether nAChR deficits in SHRs compared to Wistar Kyoto rat (WKY) controls are nAChR subtype-specific and whether these deficits correlate with changes at the level of mRNA transcription in specific brain regions. Levels of binding sites (Bmax) and dissociation constants (Kd) for nAChRs were determined from saturation curves of high-affinity [3H]epibatidine- and [3H]MLA binding to membranes from cortex, striatum, hippocampus and cerebellum. In additional brain regions, nAChRs were examined by autoradiography with [125I]A-85380 and [125I]α-bungarotoxin. Levels of mRNA encoding nAChR subunits were measured using quantitative real-time PCR (qPCR). We show that the number of α4β2 nAChR binding sites is lower globally in the SHR brain compared to WKY in the absence of significant differences in mRNA levels, with the exception of lower α4 mRNA in cerebellum of SHR compared to WKY. Further, nAChR deficits were subtype- specific because no strain difference was found in α7 nAChR binding or α7 mRNA levels. Our results suggest that the lower α4β2 nAChR number in SHR compared to WKY may be a consequence of dysfunctional post-transcriptional regulation of nAChRs. PMID:21824140

  6. Treatment of Epilepsy

    PubMed Central

    Bailey, Allan A.

    1963-01-01

    The main clinical types of epilepsy and their treatment are described. The treatment of choice in petit mal epilepsy is trimethadione (Trimedone) 0.3 g., three to six times a day, or acetazolamide (Diamox) 125-250 mg., three to four times a day. Phenobarbital is usually given as well to prevent grand mal seizures. Diphenylhydantoin sodium (Dilantin Sodium), 100 mg., and/or phenobarbital, 30-100 mg., three to four times a day, is recommended in patients with focal and grand mal epilepsy. Psychomotor automatisms are a form of focal seizure. Primidone (Mysoline), in doses of 125-250 mg. two to three times a day, is a very useful anticonvulsant in patients with myoclonic features, psychomotor automatisms and grand mal seizures. Primidone should be started in small doses. Drug reactions, especially cerebellar ataxia in the case of diphenylhydantoin and blood dyscrasias in the case of some drugs, should be recognized. Excessive drowsiness can be avoided by proper dosage and proper timing of drug administration. Patients should be seen regularly at least two to three times a year. The objective of treatment is to achieve optimum control of seizures by using the appropriate drug in adequate dosage. Social adaptation is good in the majority of patients, who should be encouraged to carry on their life independently, usually free to marry and have children. Attention to special occupational hazards has to be considered. Education of employers and employees is often necessary. Special work arrangements are occasionally indicated for selected patients. Patients should be seizure-free for two to three years before permission is given to drive an automobile. PMID:13969008

  7. Reactions of the immune system in epilepsy

    PubMed Central

    COJOCARU, Inimioara Mihaela; COJOCARU, Manole

    2010-01-01

    ABSTRACT Epilepsy may present as a symptom of many neurological disorders and often an etiological explanation cannot be identified. There is growing evidence that autoimmune mechanisms might have a role in some patients. The evidence for immunological mechanisms in epilepsy can be examined within the following three main areas: the childhood epilepsy syndromes, epilepsy associated with other immunologically mediated diseases, and the more common unselected groups of patients with epilepsy. Autoimmunity was recently suspected to be involved in the pathology of certain human epilepsies. This includes numerous reports of the detection of theoretically relevant serum autoantibodies, experimental data showing that antibodies can be epileptogenic, and a response of some epilepsy syndromes to immunomodulation. The high prevalence of epilepsies in specific immune diseases suggests that immune system may play a role in the pathogenesis of epilepsy or might be associated with it. There is some evidence that immune mechanisms play a role in the pathogenesis of some epilepsy syndromes. PMID:21977153

  8. 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".

  9. Epilepsy Surgery: An Evidence Summary

    PubMed Central

    2012-01-01

    Background The Medical Advisory Secretariat, the predecessor of Health Quality Ontario, published an evidence-based analysis on functional brain imaging. This analysis highlighted the low uptake of epilepsy surgery in Ontario and internationally. Objective The objective of this analysis was to review the effectiveness of epilepsy surgery at reducing seizure frequency, as well as the safety of epilepsy surgery. Data Sources The literature search included studies published between January 1995 and March 2012. Search terms included epilepsy, surgery, resection, safety, and complications. Review Methods Studies were eligible for inclusion if they included at least 20 patients undergoing surgery; had a comparison group of patients with epilepsy who were not undergoing surgery; and reported follow-up periods of at least 1 year. Outcomes of interest included seizure frequency and complications associated with surgery. Results Six systematic reviews reported pooled seizure-free rates that ranged from 43% to 75%. Two randomized controlled trials compared the effectiveness of epilepsy surgery with no surgery in patients with drug-refractory epilepsy. Both trials reported significant improvements in the seizure frequency in the surgery group compared with the nonsurgery group. Eight retrospective cohort studies reported on the safety of epilepsy surgery. Of the 2,725 patients included in these studies, there were 3 deaths reportedly related to surgery. Other complications included hemiparesis, infection, and visual field defects. The studies had long follow-up periods ranging from a mean of 2 to 7 years. Limitations The most recent randomized controlled trial was stopped early due to slow enrolment rates. Thus results need to be interpreted with caution. Conclusions There is high quality evidence that epilepsy surgery is effective at reducing seizure frequency. Two randomized controlled trials compared surgery to no surgery in patients with drug-refractory epilepsy. Both

  10. Clinical characteristics of children and young adults with co-occurring autism spectrum disorder and epilepsy.

    PubMed

    El Achkar, Christelle M; Spence, Sarah J

    2015-06-01

    The association between autism spectrum disorder (ASD) and epilepsy has been described for decades, and yet we still lack the full understanding of this relationship both clinically and at the pathophysiologic level. This review evaluates the available data in the literature pertaining to the clinical characteristics of patients with autism spectrum disorder who develop epilepsy and, conversely, patients with epilepsy who develop autism spectrum disorder. Many studies demonstrate an increased risk of epilepsy in individuals with ASD, but rates vary widely. This variability is likely secondary to the different study methods employed, including the study population and definitions of the disorders. Established risk factors for an increased risk of epilepsy in patients with ASD include intellectual disability and female gender. There is some evidence of an increased risk of epilepsy associated with other factors such as ASD etiology (syndromic), severity of autistic features, developmental regression, and family history. No one epilepsy syndrome or seizure type has been associated, although focal or localization-related seizures are often reported. The age at seizure onset can vary from infancy to adulthood with some evidence of a bimodal age distribution. The severity and intractability of epilepsy in populations with ASD have not been well studied, and there is very little investigation of the role that epilepsy plays in the autism behavioral phenotype. There is evidence of abnormal EEGs (especially epileptiform abnormalities) in children with ASD even in the absence of clinical seizures, but very little is known about this phenomenon and what it means. The development of autism spectrum disorder in patients with epilepsy is less well studied, but there is evidence that the ASD risk is greater in those with epilepsy than in the general population. One of the risk factors is intellectual disability, and there is some evidence that the presence of a particular seizure

  11. Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy.

    PubMed

    Aronica, E; van Vliet, E A; Hendriksen, E; Troost, D; Lopes da Silva, F H; Gorter, J A

    2001-11-01

    Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up-regulation was also observed in neuronal cells within one day after SE. Up-regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3-8 months post-SE). This study demonstrates that status epilepticus leads to a widespread and persistent up-regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.

  12. 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.

  13. 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

  14. Treatment of epilepsy in adults.

    PubMed

    Burakgazi, Evren; French, Jacqueline A

    2016-09-01

    Epilepsy is a chronic neurological disorder in adults and requires treatment with antiepileptic medication. While the majority of patients with epilepsy can be treated with medication, about one third will fail on medical treatment. Therefore, other treatment options such as surgery, devices, and the ketogenic diet are other options to consider, in addition to medical treatment. The treatment of epilepsy requires many other factors to be taken into consideration, and these include, but are not limited to, age, gender, coexistent medical conditions, and the use of concomitant medications. The goal of treatment is to provide optimal seizure control while using the least possible number of medications, particularly for young females at reproductive age or the elderly who may suffer from other medical diseases and receive other concomitant medications. Certain conditions may co-exist with epilepsy, such as migraine, mood disorder, and memory disturbances, therefore the decision to choose the most appropriate medication for epilepsy patients should also involve treatment of these conditions. Here, we review current clinical practice in epilepsy and focus on the most common problems and conditions that clinicians face on a daily basis to treat adult patients with epilepsy. Side effect profiles, spectrum of efficacy and optimal choices per predominant type of seizures are summarized and can be used for educational purposes.

  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.

  16. Managing epilepsy in pregnancy.

    PubMed

    Thomas, Sanjeev V

    2011-01-01

    There are close to one and half million women with epilepsy (WWE) in reproductive age group in India. WWE have several unique gender-specific problems in the biological and social domains. Women experience more social stigma from epilepsy and have more difficulty with education and employment. They have more difficulty to get married and sustain successful family life. Reproductive hormones like estrogen and progesterone have opposing effect on seizure threshold. WWE have increased risk of infertility. About 10% of their babies may have major congenital malformations. Most of the adverse biological outcomes for WWE are related to adverse effects of antiepileptic drugs (AEDs). Traditional AEDs like phenobarbitone and sodium valproate are probably associated with increased risk of fetal malformations or other adverse fetal outcomes. Polytherapy and use of high dose of any AED is associated with higher risk fetal complications. It is very important that all WWE have a preconception evaluation done by a neurologist, when the need to continue AEDs or possibility of reducing AED load could be assessed. All WWE need to take folic acid 5 mg daily during preconception period and pregnancy. They should undergo a detailed screening for fetal malformations between 12 and 18 weeks of pregnancy. The neurologist, gynecologist, imageologist and pediatrician need to work as a team while managing pregnancy in WWE. It is important to reassure WWE and their relatives that pregnancy is safe in WWE and their children are healthy in more than 90% instances.

  17. Phenotype definition in epilepsy.

    PubMed

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  18. 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

  19. [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.

  20. Review of systems questionnaire helps differentiate psychogenic nonepileptic seizures from epilepsy.

    PubMed

    Asadi-Pooya, Ali A; Rabiei, Amin H; Tinker, Jennifer; Tracy, Joseph

    2016-12-01

    We investigated the utility of a very brief review of system (ROS) questionnaire in differentiating psychogenic nonepileptic seizures (PNES) from epilepsy. In this retrospective study, we investigated all patients with PNES admitted to Jefferson Comprehensive Epilepsy Center from October 2013 through April 2015. Patients with a confirmed diagnosis of PNES or epilepsy based on video-EEG monitoring were included. These were matched with respect to age and sex. All patients had a brief ROS questionnaire in their electronic charts. The questionnaire included 10 general yes/no questions about the presence or absence of any abnormality in body systems. Thirty patients with PNES and 30 patients with epilepsy were investigated. The mean of ROS responses for the presence of any abnormality (±standard deviation) for the PNES group was 2.43 (±1.33) and for the epilepsy group was 1.50 (±0.94) (p=0.01). Cut-off point of three positive ROS was able to differentiate these two conditions from each another (p=0.01; OR: 6, 95% confidence interval: 1.48-24.29). Presence of multiple complaints in the ROS questionnaire argues in favor of PNES compared with epilepsy. This brief and easy to apply ROS questionnaire may be used as a valuable ancillary tool to differentiate PNES from epilepsy during the initial screening visit. This may help prevent the delay in making the diagnosis.

  1. [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.

  2. 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 6-16 years), 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.

  3. Refractory epilepsy and the ketogenic diet: pathophysiological aspects and possible implications in dental practice.

    PubMed

    Sharma, A; Mathur, V P

    2011-01-01

    Epilepsy denotes any disorder characterized by recurrent seizures due to abnormal paroxysmal neuronal discharge in the brain. Symptoms range from sensory absences to convulsive movements and loss of consciousness. Antiepileptic drugs are the first line of treatment. However, 20% individuals with epilepsy have drug-resistant seizures despite optimal treatment. For those with refractory epilepsy, the ketogenic diet is an effective alternative therapeutic approach. The ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet that mimics the biochemical effects of fasting. There are many disparate mechanistic theories of how this diet protects against seizures. Key insights indicate that it has effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in brain. This paper discusses the implicitly significant and diverse biochemical changes affected by this unique therapeutic approach that may have a bearing on oral health and the delivery of dental care to individuals with refractory epilepsy.

  4. What resources? Addressing the needs of the epilepsy community.

    PubMed

    Brown, S W

    1995-09-01

    Epilepsy is a condition which spans several disciplines within medicine, as well as having an impact on many non-medical areas such as employment and education. Services for epilepsy in the UK have not been developed according to any coherent strategy and remain fragmented and unevenly distributed. Successive attempts to address these shortcomings by publishing recommendations, even with government assistance, have not led to major improvements. Recent changes in the organization of health care services might at least present an opportunity to effect change by educational initiatives directed towards purchasers and providers. However, the absence of epilepsy from The Health of the Nation objectives represents a failure to get the message through to those with the ability to direct policy. The plethora of new, effective and expensive pharmaceutical treatments should lead to a raising of epilepsy awareness among the medical profession as a consequence of marketing activity, but this is already causing conflict with Family Health Service Associations (FHSAs) and others with equivalent lack of vision. I would suggest that only by politicizing the consumer can the change we seek be brought about.

  5. 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.

  6. Calmodulin regulates KCNQ2 function in epilepsy

    PubMed Central

    Zhou, Xuhong; Zhuang, Fei; Li, Hong; Zheng, Kun; Hong, Ze; Feng, Weijing; Zhou, Wendi; Chen, Jian

    2016-01-01

    Epilepsy is linked to mutations in KCNQ channels. KCNQ channels including KCNQ2 and KCNQ3 are enriched in neurons, regulating action potential generation and modulation. Here, we showed that properties of KCNQ2 channel in rat hippocampal cultured neurons are regulated by ubiquitous calcium sensor calmodulin. We analyzed calmodulin function on the KCNQ2 channel in both HEK293 cells and neurons. We used shRNAs to suppress expression of calmodulin protein. On the other hand, we used cDNA to over-express calmodulin in HEK293 and neuron cells. In wild type and mis-sense mutations of KCNQ2 proteins, calmodulin over-expression enhanced outward K+ current and decreased neuronal activity. Meanwhile, calmodulin knockdown reduced KCNQ2 current and increased neuronal activity, showing that hippocampal neuronal excitability is regulated by expression level of calmodulin protein. Our data suggest that calmodulin performs a major function in regulating KCNQ2 properties via direct binding to KCNQ2 protein, indicating that calmodulin could be a target of as gene therapy in epilepsy. PMID:28078031

  7. 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

  8. [Modern aspects of epilepsy treatment].

    PubMed

    Alajbegović, Azra; Kantardzić, Dzelaludin; Suljić, Enra; Alajbegović, Salem

    2003-01-01

    It is a general rule today, after a relevant diagnostics of an epilepsy, to start a monotherapy treatment, depending on a kind of a seizure, a life age and a general health condition. First line of monotherapy epilepsy drugs remain carbamazapine and sodium valproat. New drugs that are being introduced are: felbamat, gabapentin, lamotrigin, oxcarbazepin, tiagabin, topiramat, vigabatin and zanisamid. These are commonly used as add-on therapy, or as an addition for previously used antiepileptic. Their indicated areas are complex resistant partial seizures with or without generalization. Attention should be paid on proper dosage, interactions and toxicity. Regardless on the new epileptic era, according to reports of International League against epilepsy, most of the patients do not receive the drug that is the most appropriate for them concerning the price (cost-benefit). Neurosurgical methods in epilepsy treatment are: selective amygdalo-hyppocampotomy, temporal lobotomy, subpial resection, hemispherectomy, corpus callosotomy, removal of lesions like tumors or cysts provide encouraging results in reduction of epileptic seizures that can be followed by reduction of drug therapy. N. vagus stimulation is being wider introduced in resident epileptics. Treatment of epilepsy in women requires an approach to sexuality, conception, pregnancy, introduction of medicaments, antiepileptic terratogenity, contraception, motherhood and menopause. A special significance of modern approach to epilepsy is in treatment of elderly who have cerebrovascular and neurodegenerative disease as a cause of seizures. A complex treatment of epilepsy using pharmacological and neurosurgical approach requires supportive psychotherapy, socio-therapy, the work with a family, education about epilepsy and living a life with more quality having one.

  9. Video material and epilepsy.

    PubMed

    Harding, G F; Jeavons, P M; Edson, A S

    1994-01-01

    Nine patients who had epileptic attacks while playing computer games were studied in the laboratory. Patients had an EEG recorded as well as their response to intermittent photic stimulation (IPS) at flash rates of 1-60 fps. In addition, pattern sensitivity was assessed in all patients by a gratings pattern. Only 2 patients had no previous history of convulsions, and only 2 had a normal basic EEG. All but 1 were sensitive to IPS, and all but 1 were pattern sensitive. Most patients were male, but although this appears to conflict with previously published literature results regarding the sex ratio in photosensitivity, it was due to the male predominance of video game usage. We compared our results with those reported in the literature. Diagnosing video game epilepsy requires performing an EEG with IPS and pattern stimulation. We propose a standard method of testing.

  10. The Managing Epilepsy Well Network:: Advancing Epilepsy Self-Management.

    PubMed

    Sajatovic, Martha; Jobst, Barbara C; Shegog, Ross; Bamps, Yvan A; Begley, Charles E; Fraser, Robert T; Johnson, Erica K; Pandey, Dilip K; Quarells, Rakale C; Scal, Peter; Spruill, Tanya M; Thompson, Nancy J; Kobau, Rosemarie

    2017-03-01

    Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two

  11. 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.

  12. Why epilepsy challenges social life.

    PubMed

    Steiger, Bettina K; Jokeit, Hennric

    2017-01-01

    Social bonds are at the center of our daily living and are an essential determinant of our quality of life. In people with epilepsy, numerous factors can impede cognitive and affective functions necessary for smooth social interactions. Psychological and psychiatric complications are common in epilepsy and may hinder the processing of social information. In addition, neuropsychological deficits such as slowed processing speed, memory loss or attentional difficulties may interfere with enjoyable reciprocity of social interactions. We consider societal, psychological, and neuropsychological aspects of social life with particular emphasis on socio-cognitive functions in temporal lobe epilepsy. Deficits in emotion recognition and theory of mind, two main aspects of social cognition, are frequently observed in individuals with mesial temporal lobe epilepsy. Results from behavioural studies targeting these functions will be presented with a focus on their relevance for patients' daily life. Furthermore, we will broach the issue of pitfalls in current diagnostic tools and potential directions for future research. By giving a broad overview of individual and interpersonal determinants of social functioning in epilepsy, we hope to provide a basis for future research to establish social cognition as a key component in the comprehensive assessment and care of those with epilepsy.

  13. Epilepsy in children with trisomy 18.

    PubMed

    Kumada, Tomohiro; Maihara, Toshiro; Higuchi, Yoshihisa; Nishida, Yoshinobu; Taniguchi, Yoshihiro; Fujii, Tatsuya

    2013-04-01

    Although the reported incidence of epilepsy associated with trisomy 18 is 25-50%, there have been no detailed descriptions of the characteristics of trisomy 18-related epilepsy. We investigated the characteristics of epilepsy in children with trisomy 18 who remained alive for over 1 year by sending questionnaires to pediatric neurologists belonging to the Kyoto Multi-institutional Study Group of Pediatric Neurology. Eleven patients with trisomy 18 were enrolled (age at the study, from 15 to 134 months; median, 43 months), of whom seven (64%) had epilepsy. The age at seizure onset ranged from 1 to 42 months (median: 11 months). Among the seven patients with epilepsy, two had focal epilepsy, four had generalized epilepsy including infantile spasms in three, and the remaining one had an unclassified type. Seizure seminology included complex partial seizures in both the patients with focal epilepsy. At the time of the investigation, three children with generalized epilepsy still had daily seizures, while the remaining four were seizure-free. In conclusion, the characteristics of epilepsy in patients with trisomy 18 were as follows: over half of the children developed epilepsy during infancy or early childhood; infantile spasms might be one of the common epileptic syndromes; the epilepsy was intractable in half of the children, especially in those with generalized epilepsy.

  14. Subependymal heterotopia: a distinct neuronal migration disorder associated with epilepsy.

    PubMed Central

    Raymond, A A; Fish, D R; Stevens, J M; Sisodiya, S M; Alsanjari, N; Shorvon, S D

    1994-01-01

    Subependymal heterotopia has recently been recognised as a cause of epilepsy, but the clinical and investigational features have not been fully described. The clinical, psychometric, imaging, and electroencephalographic features of 13 adult patients with subependymal heterotopia and epilepsy have been reviewed. Age at seizure onset ranged from 18 months to 20 years (median 13 years). There were significantly more female (12) than male (1) patients (p < 0.01). Diagnosis of subependymal heterotopia was made by MRI in 11 patients and CT in two. The heterotopic grey matter was nodular in 11 patients and diffuse in two; bilateral in eight and unilateral in five. There were significantly more patients with predominant right than left cerebral hemisphere involvement (p < 0.01). The most commonly involved site was the occipital horn of the lateral ventricles (10 of 13 patients). Eleven patients presented with partial epilepsy, 10 of whom also had secondarily generalised seizures. The clinical description of the seizures often suggested either an occipital (four patients) or temporal (five patients) onset. Two patients presented with absence attacks without clear focal features. Patients demonstrated normal early milestones (12 of 13 patients), including normal motor development (all patients) and average or above average intelligence (10 of 13 patients). An EEG examination showed normal background activity in all but two patients, one of whom had large intracranial haematomas. Epileptiform activity was usually widespread (10 of 13 patients) and in three patients, there was generalised 3-Hz spike and wave activity that had previously led to an erroneous diagnosis of concomitant primary generalised epilepsy. Onset of epilepsy in the second decade of life, normal developmental milestones and intelligence, and the finding of an overwhelming female preponderance differentiates subependymal heterotopia from other cortical dysgeneses. The female preponderance supports the

  15. Does antiepileptogenesis affect sleep in genetic epileptic rats?

    PubMed

    van Luijtelaar, Gilles; Wilde, Matthias; Citraro, Rita; Scicchitano, Francesca; van Rijn, Clementina

    2012-07-01

    Recently it was established that early long lasting treatment with the anti-absence drug ethosuximide (ETX) delays the occurrence of absences and reduces depressive-like symptoms in a genetic model for absence epilepsy, rats of the WAG/Rij strain. Here it is investigated whether anti-epileptogenesis (chronic treatments with ETX for 2 and 4 months) affects REM sleep in this model. Four groups of weaned male WAG/Rij rats were treated with ETX for 4 months, two groups for 2 months (at 2-3 and 4-5 months of age), the fourth group was untreated. Next, the rats were recorded 6 days after the last day of the treatment for 22.5 h. Non-REM sleep and REM sleep parameters and delta power were analyzed in four characteristic and representative hours of the recoding period. Four months treatment with ETX reduced the amount of REM sleep and REM sleep as percentage of total sleep time. Other sleep parameters were not affected by the treatment. Clear differences between the various hours of the light-dark phase in amounts of non-REM and REM sleep and delta power were found, in line with commonly reported circadian sleep patterns. It can be concluded that the reduction of REM sleep is unique for the early and long lasting chronic treatment. The outcomes may explain our earlier finding that a reduction of REM sleep might alleviate depressive like symptoms.

  16. Effects of modafinil on pentylenetetrazol-induced convulsive epilepsy.

    PubMed

    Ozsoy, S; Aydin, D; Ekici, F

    2015-01-01

    Modafinil, is a wake-promoting drug approved by Food and Drugs Administration (FDA) for narcolepsy and sleep-apnoe syndrome. Although the mechanism underlying its arousal action remains elusive, it is known to increase glutamatergic, histaminergic, noradrenergic and dopaminergic transmission and decrease GABA release in different regions of the brain, which are all known to be involved in pathophysiology of epilepsy. In the present study, the effects of modafinil on pentylenetetrazol (PTZ) induced convulsive epilepsy were investigated in rats. Five experimental groups were formed for this purpose and each group was administered five different doses of modafinil (1, 2, 4, 45, 180 mg/kg, i.p) for seven days. All groups were administered PTZ (80 mg/kg, i.p) 2 hours after the final dose and the epileptic seizure activity was evaluated. According to the results; we detected that modafinil delayed the onset of the first myoclonic jerk and decreased the total major seizure period between 2-180 mg/kg doses and did not affect the major seizure onset period at any of the doses administrated. These results imply that modafinil exerts a dose dependent antiepileptic effect on PTZ induced convulsive epilepsy in rats (Tab. 1, Fig. 3, Ref, 42).

  17. Personalized medicine approaches in epilepsy.

    PubMed

    Walker, L E; Mirza, N; Yip, V L M; Marson, A G; Pirmohamed, M

    2015-02-01

    Epilepsy affects 50 million persons worldwide, a third of whom continue to experience debilitating seizures despite optimum anti-epileptic drug (AED) treatment. Twelve-month remission from seizures is less likely in female patients, individuals aged 11-36 years and those with neurological insults and shorter time between first seizure and starting treatment. It has been found that the presence of multiple seizures prior to diagnosis is a risk factor for pharmacoresistance and is correlated with epilepsy type as well as intrinsic severity. The key role of neuroinflammation in the pathophysiology of resistant epilepsy is becoming clear. Our work in this area suggests that high-mobility group box 1 isoforms may be candidate biomarkers for treatment stratification and novel drug targets in epilepsy. Furthermore, transporter polymorphisms contributing to the intrinsic severity of epilepsy are providing robust neurobiological evidence on an emerging theory of drug resistance, which may also provide new insights into disease stratification. Some of the rare genetic epilepsies enable treatment stratification through testing for the causal mutation, for example SCN1A mutations in patients with Dravet's syndrome. Up to 50% of patients develop adverse reactions to AEDs which in turn affects tolerability and compliance. Immune-mediated hypersensitivity reactions to AED therapy, such as toxic epidermal necrolysis, are the most serious adverse reactions and have been associated with polymorphisms in the human leucocyte antigen (HLA) complex. Pharmacogenetic screening for HLA-B*15:02 in Asian populations can prevent carbamazepine-induced Stevens-Johnson syndrome. We have identified HLA-A*31:01 as a potential risk marker for all phenotypes of carbamazepine-induced hypersensitivity with applicability in European and other populations. In this review, we explore the currently available key stratification approaches to address the therapeutic challenges in epilepsy.

  18. Vagus Nerve Stimulation for Treating Epilepsy

    MedlinePlus

    ... Evidence-based Guideline for PATIENTS and their FAMILIES VAGUS NERVE STIMULATION FOR TREATING EPILEPSY This information sheet is provided to help you understand how vagus nerve stimulation (VNS) may help treat epilepsy. The American ...

  19. 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

  20. PET studies in epilepsy.

    PubMed

    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. (18)Fluoro-2-deoxyglucose ((18)F-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 (11)C-flumazenil (GABAA-cBDZ) and (18)F-MPPF (5-HT1A serotonin) and increased (11)C-cerfentanil (mu opiate) and (11)C-MeNTI (delta opiate) bindings in the area of seizure. (11)C-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 (11)C-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

  1. 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

  2. Sleep-related hypermotor epilepsy

    PubMed Central

    Licchetta, Laura; Vignatelli, Luca; Zenesini, Corrado; Di Vito, Lidia; Mostacci, Barbara; Rinaldi, Claudia; Trippi, Irene; Naldi, Ilaria; Plazzi, Giuseppe; Provini, Federica; Tinuper, Paolo

    2017-01-01

    Objective: To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE). Methods: We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed. Results: We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26–14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31–5.85, p = 0.008) were associated with TR. Conclusions: Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology. PMID:27881627

  3. Epilepsy services in Saudi Arabia

    PubMed Central

    Alfayez, Saud M.; Aljafen, Bandar N.

    2016-01-01

    Objective: To assess the epilepsy services and identify the challenges in hospitals without epilepsy monitoring units (EMUs). In addition, comparisons between governmental and private sectors, as well as between regions, are to be performed. Methods: A cross-sectional study conducted using an online questionnaire distributed to the secondary and tertiary hospitals without EMUs throughout the Kingdom of Saudi Arabia (KSA). The study was conducted from September 2013 to September 2015 and regular updates from all respondents were constantly made. Items in the questionnaire included the region of the institution, the number of pediatric and adult neurologists and neurosurgeons along with their subspecialties, the number of beds in the Neurology Department, whether they provide educational services and have epilepsy clinics and if they refer patients to an EMU or intend to establish one in the future. Results: Forty-three institutions throughout the Kingdom responded, representing a response rate of 54%. The majority of hospitals (58.1%) had no adult epileptologists. A complete lack of pediatric epileptologists was observed in 72.1% of hospitals. Around 39.5% were utilizing beds from internal medicine. Hospitals with an epilepsy clinic represented 34.9% across all regions and sectors. Hospitals with no intention of establishing an EMU represented 53.5%. Hospitals that did not refer their epileptic patients to an EMU represented 30.2%. Conclusions: Epilepsy services in KSA hospitals without EMUs are underdeveloped. PMID:27744461

  4. Absence Seizure (Petit Mal Seizure)

    MedlinePlus

    ... Staff Absence seizures involve brief, sudden lapses of consciousness. They're more common in children than adults. ... have seizures, the brain's usual electrical activity is altered. During an absence seizure, these electrical signals repeat ...

  5. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

    PubMed Central

    de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah; Møller, Rikke S; Velinov, Milen; Dolzhanskaya, Natalia; Marsh, Eric; Helbig, Ingo; Devinsky, Orrin; Tang, Sha; Mefford, Heather C; Myers, Candace T; van Paesschen, Wim; Striano, Pasquale; van Gassen, Koen; van Kempen, Marjan; de Kovel, Carolien G F; Piard, Juliette; Minassian, Berge A; Nezarati, Marjan M; Pessoa, André; Jacquette, Aurelia; Maher, Bridget; Balestrini, Simona; Sisodiya, Sanjay; Warde, Marie Therese Abi; De St Martin, Anne; Chelly, Jamel; van ‘t Slot, Ruben; Van Maldergem, Lionel; Brilstra, Eva H; Koeleman, Bobby P C

    2016-01-01

    Background Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Methods Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. Results All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Conclusions Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy. PMID:27358180

  6. 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.

  7. Altered Oscillatory Dynamics of CA1 Parvalbumin Basket Cells during Theta-Gamma Rhythmopathies of Temporal Lobe Epilepsy.

    PubMed

    Lopez-Pigozzi, Diego; Laurent, François; Brotons-Mas, Jorge R; Valderrama, Mario; Valero, Manuel; Fernandez-Lamo, Ivan; Cid, Elena; Gomez-Dominguez, Daniel; Gal, Beatriz; Menendez de la Prida, Liset

    2016-01-01

    Recent reports in human demonstrate a role of theta-gamma coupling in memory for spatial episodes and a lack of coupling in people experiencing temporal lobe epilepsy, but the mechanisms are unknown. Using multisite silicon probe recordings of epileptic rats engaged in episodic-like object recognition tasks, we sought to evaluate the role of theta-gamma coupling in the absence of epileptiform activities. Our data reveal a specific association between theta-gamma (30-60 Hz) coupling at the proximal stratum radiatum of CA1 and spatial memory deficits. We targeted the microcircuit mechanisms with a novel approach to identify putative interneuronal types in tetrode recordings (parvalbumin basket cells in particular) and validated classification criteria in the epileptic context with neurochemical identification of intracellularly recorded cells. In epileptic rats, putative parvalbumin basket cells fired poorly modulated at the falling theta phase, consistent with weaker inputs from Schaffer collaterals and attenuated gamma oscillations, as evaluated by theta-phase decomposition of current-source density signals. We propose that theta-gamma interneuronal rhythmopathies of the temporal lobe are intimately related to episodic memory dysfunction in this condition.

  8. Altered Oscillatory Dynamics of CA1 Parvalbumin Basket Cells during Theta–Gamma Rhythmopathies of Temporal Lobe Epilepsy

    PubMed Central

    Laurent, François; Brotons-Mas, Jorge R.; Valderrama, Mario; Fernandez-Lamo, Ivan; Gomez-Dominguez, Daniel; Gal, Beatriz

    2016-01-01

    Abstract Recent reports in human demonstrate a role of theta–gamma coupling in memory for spatial episodes and a lack of coupling in people experiencing temporal lobe epilepsy, but the mechanisms are unknown. Using multisite silicon probe recordings of epileptic rats engaged in episodic-like object recognition tasks, we sought to evaluate the role of theta–gamma coupling in the absence of epileptiform activities. Our data reveal a specific association between theta–gamma (30–60 Hz) coupling at the proximal stratum radiatum of CA1 and spatial memory deficits. We targeted the microcircuit mechanisms with a novel approach to identify putative interneuronal types in tetrode recordings (parvalbumin basket cells in particular) and validated classification criteria in the epileptic context with neurochemical identification of intracellularly recorded cells. In epileptic rats, putative parvalbumin basket cells fired poorly modulated at the falling theta phase, consistent with weaker inputs from Schaffer collaterals and attenuated gamma oscillations, as evaluated by theta-phase decomposition of current–source density signals. We propose that theta–gamma interneuronal rhythmopathies of the temporal lobe are intimately related to episodic memory dysfunction in this condition. PMID:27896315

  9. Resolution of obstructive sleep apnea with epilepsy surgery? Expanding the relationship between sleep and epilepsy.

    PubMed

    Foldvary-Schaefer, Nancy; Stephenson, Lisa; Bingaman, William

    2008-08-01

    Recent studies suggest a higher than expected prevalence of obstructive sleep apnea (OSA) in patients with refractory epilepsy. In some cases, treatment of OSA improves seizure control. We report a case in which clinically significant OSA disappeared after left frontal lobe resection that produced a near seizure free state. This occurred in the absence of the usual factors, such as weight or medication change or variation in polysomnography (PSG) recording methodology, that often confound the comparison of sequential PSGs over time. Our patient underwent PSG with 18-channel EEG recording pre- and postoperatively using standardized scoring techniques. Baseline testing revealed an apnea-hypopnea index (AHI) of 24 with severe oxygen desaturations reaching a nadir of 62%. Postoperative testing found both the AHI and oxygen saturation normalized as well as a marked reduction in spike rate. We hypothesize that the pathophysiology of OSA in patients with epilepsy may be impacted by frequent, extensive interictal epileptiform discharges (IEDs) and/or seizures altering upper airway control during sleep.

  10. [Possibilities of psychoprophylaxis in epilepsy].

    PubMed

    Bilikiewicz, A

    1976-01-01

    The psychiatrist should be given also their share in the prevetion of epilepsy by means of raising the psychiatric culture of the society and teaching the population the principles of mental hygiene and psychoprophylaxia. The possibilities of psychiatry in prophylactic management of patients with developed epilepsy include: 1. Energetic measures for controlling attacks which has many psychoprophylactic aspects. 2. Prevention of psychotraumatizing situations leading to secondary neurotic, psychotic and other reactions and behaviour disorders of the type of homilopathy and sociopathy, 3. Counteracting the development of mental and social disability in epileptics. Treatment of epilepsy should be conducted from its very beginning in cooperation with psychiatrists and therapeutic psychologists. The probems of prophylaxis cannot be separated from prophylactic treatment, psychotherapy sociotherapy and rehabilitation.

  11. Epilepsy and music: practical notes.

    PubMed

    Maguire, M

    2017-04-01

    Music processing occurs via a complex network of activity far beyond the auditory cortices. This network may become sensitised to music or may be recruited as part of a temporal lobe seizure, manifesting as either musicogenic epilepsy or ictal musical phenomena. The idea that sound waves may directly affect brain waves has led researchers to explore music as therapy for epilepsy. There is limited and low quality evidence of an antiepileptic effect with the Mozart Sonata K.448. We do not have a pathophysiological explanation for the apparent dichotomous effect of music on seizures. However, clinicians should consider musicality when treating patients with antiepileptic medication or preparing patients for epilepsy surgery. Carbamazepine and oxcarbazepine each may cause a reversible altered appreciation of pitch. Surgical cohort studies suggest that musical memory and perception may be affected, particularly following right temporal lobe surgery, and discussion of this risk should form part of presurgical counselling.

  12. 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".

  13. Treatment algorithms in refractory partial epilepsy.

    PubMed

    Jobst, Barbara C

    2009-09-01

    An algorithm is a "step-by-step procedure for solving a problem or accomplishing some end....in a finite number of steps." (Merriam-Webster, 2009). Medical algorithms are decision trees to help with diagnostic and therapeutic decisions. For the treatment of epilepsy there is no generally accepted treatment algorithm, as individual epilepsy centers follow different diagnostic and therapeutic guidelines. This article presents two algorithms to guide decisions in the treatment of refractory partial epilepsy. The treatment algorithm describes a stepwise diagnostic and therapeutic approach to intractable medial temporal and neocortical epilepsy. The surgical algorithm guides decisions in the surgical treatment of neocortical epilepsy.

  14. Alternative approaches to epilepsy treatment.

    PubMed

    McElroy-Cox, Caitlin

    2009-07-01

    Complementary and alternative medicine (CAM) is a diverse group of health care practices and products that fall outside the realm of traditional Western medical theory and practice and that are used to complement or replace conventional medical therapies. The use of CAM has increased over the past two decades, and surveys have shown that up to 44% of patients with epilepsy are using some form of CAM treatment. This article reviews the CAM modalities of meditation, yoga, relaxation techniques, biofeedback, nutritional and herbal supplements, dietary measures, chiropractic care, acupuncture, Reiki, and homeopathy and what is known about their potential efficacy in patients with epilepsy.

  15. 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

  16. Spirituality and religion in epilepsy.

    PubMed

    Devinsky, Orrin; Lai, George

    2008-05-01

    Revered in some cultures but persecuted by most others, epilepsy patients have, throughout history, been linked with the divine, demonic, and supernatural. Clinical observations during the past 150 years support an association between religious experiences during (ictal), after (postictal), and in between (interictal) seizures. In addition, epileptic seizures may increase, alter, or decrease religious experience especially in a small group of patients with temporal lobe epilepsy (TLE). Literature surveys have revealed that between .4% and 3.1% of partial epilepsy patients had ictal religious experiences; higher frequencies are found in systematic questionnaires versus spontaneous patient reports. Religious premonitory symptoms or auras were reported by 3.9% of epilepsy patients. Among patients with ictal religious experiences, there is a predominance of patients with right TLE. Postictal and interictal religious experiences occur most often in TLE patients with bilateral seizure foci. Postictal religious experiences occurred in 1.3% of all epilepsy patients and 2.2% of TLE patients. Many of the epilepsy-related religious conversion experiences occurred postictally. Interictal religiosity is more controversial with less consensus among studies. Patients with postictal psychosis may also experience interictal hyper-religiosity, supporting a "pathological" increase in interictal religiosity in some patients. Although psychologic and social factors such as stigma may contribute to religious experiences with epilepsy, a neurologic mechanism most likely plays a large role. The limbic system is also often suggested as the critical site of religious experience due to the association with temporal lobe epilepsy and the emotional nature of the experiences. Neocortical areas also may be involved, suggested by the presence of visual and auditory hallucinations, complex ideation during many religious experiences, and the large expanse of temporal neocortex. In contrast to the

  17. Are cannabinoids effective for epilepsy?

    PubMed

    Peña, Javier; Rada, Gabriel

    2017-01-13

    Several beneficial effects have been proposed for cannabinoids in different clinical conditions, including epilepsy. However, their clinical role is controversial. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified five systematic reviews including four randomized trials addressing the question of this article. We extracted data and generated a summary of findings following the GRADE approach. We concluded it is not clear whether cannabinoids reduce the frequency of seizures in epilepsy because the certainty of the evidence is very low, and they probably increase adverse effects.

  18. [Insular epilepsy: The Montreal experience].

    PubMed

    Nguyen, D K; Surbeck, W; Weil, A G; Villemure, J-G; Bouthillier, A

    2009-10-01

    In this article, we review recently published data on the role of the insula in refractory partial epilepsy and summarize our own experience in the investigation and treatment of this entity. Case studies and evoked responses obtained from insular cortical stimulation reveal a wide array of clinical manifestations which may mimic temporal, frontal or parietal lobe seizures. Clinicians should hence lower their threshold to sample the insula with intracerebral electrodes. Lack of recognition of insular seizures may explain part of epilepsy surgery failures. Advances in microneurosurgery open the way to safer insular resection.

  19. P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.

    PubMed

    Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern

    2017-03-02

    A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.

  20. Pediatric Epilepsy: Neurology, Functional Imaging, and Neurosurgery.

    PubMed

    Mountz, James M; Patterson, Christina M; Tamber, Mandeep S

    2017-03-01

    In this chapter we provide a comprehensive review of the current role that functional imaging can have in the care of the pediatric epilepsy patient from the perspective of the epilepsy neurologist and the epilepsy neurosurgeon. In the neurology section, the diagnosis and classification of epilepsy adapted by the International League Against Epilepsy as well as the etiology and incidence of the disease is presented. The neuroimaging section describes how advanced nuclear medicine imaging methods can be synergized to provide a maximum opportunity to localize an epileptogenic focus. This section described the value of FDG-PET and regional cerebral blood flow SPECT in the identification of an epileptogenic focus. The imaging section also emphasizes the importance on developing a dedicated epilepsy management team, comprised of an epilepsy imaging specialist, epilepsy neurologist and epilepsy neurosurgeon, to provide the maximum benefit to each child with epilepsy. An emphasis is placed on preparation for ictal SPECT injection procedures, including the critical role of an automated injector well as the use of state-of-the-art dedicated nuclear medicine imaging and analysis protocols to correctly localize the epileptogenic focus location. In the final section, surgical options, approaches and expected outcomes for the different classes of epilepsy is presented.

  1. The relevance of kindling for human epilepsy.

    PubMed

    Bertram, Edward

    2007-01-01

    Kindling is one of the most widely used models of seizures and epilepsy, and it has been used in its more than three decade history to provide many key insights into seizures and epilepsy. It remains a mainstay of epilepsy related research, but the question remains how the results from kindling experiments further our understanding of the underlying neurobiology of human epilepsy. In this article we compare the basic features of kindling and human epilepsy, especially human limbic or temporal lobe epilepsy. In this review we focus on a limited number of topics that may show areas in which kindling has been often cited as a tool for better understanding of human epilepsy. These areas include the underlying circuits, the importance of seizure spontaneity, the associated neuropathology, the contribution of genetics, seizure susceptibility, and the underlying pathophysiology of epilepsy. In the course of this article we will show that there are many features that kindling can teach us by direct comparison or implication about human temporal epilepsy. We will also see that not all findings associated with kindling may be applicable to the human condition. Ultimately we wish to encourage critical thinking about kindling and the similarities that it shares and does not share with the human epilepsy so the results from studies using this model are applied rationally to further our insights the mechanisms of human epilepsy.

  2. 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.

  3. [Specific medico-social supports for drug-resistant partial epilepsies].

    PubMed

    Gonnaud, P-M

    2004-06-01

    While employment appears to be among major concerns for epileptic patients, these are confronted with a very high rate of unemployment, especially when epilepsy is pharmacoresistant. However, the persistence of seizures is not the only factor bearing on vocational training or employment; other factors may intervene as well: cognitive dysfunctions, psychological/behavioral disturbances, impact of AEDs, education, vocational training, family members and relatives' attitude, school teams' attitude, employers' attitude, occupational physicians' attitude. Educational level is lower when epilepsy started at school-age; persisting seizures together with other problems may lead the epileptic child or teenager to attend specialized schools. In France, there are few institutions dedicated to children or teenagers with severe epilepsy, and these are very unevenly distributed over the French territory. The main social measures regarding children with epilepsy in France are mentioned. Besides being seizure-free and able to drive, work is one major expectation of patients from epilepsy surgery. The results of epilepsy surgery regarding employment are somewhat controversial; in some studies, temporal lobe surgery may not raise the employment rate; other studies point out that operated-on patients need a long time (up to 6 years) to find a job after surgery. The vocational level or the previous work experiences appear to be as important factors for further employment as being seizure-free, a condition which may not be met in all favourable work outcomes. The medico-social support to patients with pharmacoresistant partial epilepsies has to deal with all the factors mentioned previously; the opportunity for epilepsy surgery may have to be considered early in order to try and prevent the detrimental impact of pharmacoresistant epilepsy on school achievement and vocational training; adult patients with pharmacoresistant epilepsy often cumulate a low qualification level, an absence of

  4. 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

  5. Writing epilepsy: a neurophysiological, neuropsychological and neuroimaging study.

    PubMed

    Abreu, Pedro; Ribeiro, Mendes; Forni, Alessandra; Pires, Isabel; Sousa, Georgina

    2005-05-01

    Writing epilepsy is a rare reflex syndrome in which seizures are triggered by writing. We describe a 33-year-old, right-handed man, with a history of juvenile absence epilepsy in remission and a family history of epilepsy, in whom myoclonic jerks precipitated exclusively by writing started at the age of 30. Intensive video/EEG monitoring during neuropsychological tests revealed, at about 1 minute after starting to write, a dystonic posture, followed by myoclonic jerks involving the right hand that shortly after became generalized. Concomitantly, the ictal EEG documented generalized hypersynchronous polyspike-wave discharges, maximal over the right parietocentral area. SPECT revealed an ictal hyperperfusion and interictal hypoperfusion over right parietofrontal regions, and fMRI showed extensive and intense left frontal, supplementary motor area activation, induced by writing. This case study provides some evidence supporting the hypothesis that the mechanism underlying writing-triggered seizures may be a generalized seizure process, with a focal cortical trigger zone, presumed to be the left frontal lobe as suggested by clinical and fMRI data. A relevant role played by the right hemisphere (right parietofrontal region) is postulated in the full-blown expression of reflex epileptogenesis, as supported by EEG and SPECT findings.

  6. Corpus callosotomy in a patient with startle epilepsy.

    PubMed

    Gómez, Nicolás Garófalo; Hamad, Ana Paula; Marinho, Murilo; Tavares, Igor M; Carrete, Henrique; Caboclo, Luís Otávio; Yacubian, Elza Márcia; Centeno, Ricardo

    2013-03-01

    Startle epilepsy is a syndrome of reflex epilepsy in which the seizures are precipitated by a sudden and surprising, usually auditory, stimulus. We describe herein a girl who had been suffering with startle-induced seizures since 2 years of age. She had focal, tonic and tonic-clonic seizures, refractory to antiepileptic treatment. Daily tonic seizures led to very frequent falls and morbidity. Neurologically, she had no deficit. Interictal EEG showed slow waves and epileptiform discharges in central and fronto-central regions. Video-polygraphic recordings of seizures, triggered by stimuli, showed generalised symmetric tonic posturing with ictal EEG, characterised by an abrupt and diffuse electrodecremental pattern of fast activity, followed by alpha-theta rhythm superimposed by epileptic discharges predominantly over the vertex and anterior regions. Magnetic resonance imaging showed no abnormalities. Corpus callosotomy was performed when the patient was 17. Since surgery, the patient (one year follow-up) has remained seizure-free. Corpus callosotomy may be considered in patients with startle epilepsy and tonic seizures, in the absence of focal lesions amenable to surgery. [Published with video sequences].

  7. 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.

  8. 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…

  9. 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…

  10. Epilepsy in Adults with TSC

    MedlinePlus

    ... have epilepsy is to achieve the best seizure control possible while maintaining the best quality of life. If individuals with TSC experience an ... be the advocate to achieve the best seizure control possible while also optimizing the ... quality of life. Health care providers should remember that ...

  11. Chronic temporal lobe epilepsy: a neurodevelopmental or progressively dementing disease?

    PubMed

    Helmstaedter, C; Elger, C E

    2009-10-01

    dementing decline in chronic TLE patients. During childhood, and even more so during the decade following puberty, the critical phases for establishing episodic memory deficits appear. This increases the risk of premature 'dementia' later on, even in the absence of an accelerated decline. Material specific verbal memory impairment in left TLE is a characteristic of the mature brain and seems to disappear at an older age. The findings suggest that increased attention is to be paid to the time of epilepsy onset and thereafter. Early control of epilepsy is demanded to counteract developmental hindrance and damage at a younger age.

  12. Consciousness as a useful concept in epilepsy classification.

    PubMed

    Blumenfeld, Hal; Meador, Kimford J

    2014-08-01

    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 consciousness in

  13. Genetics Home Reference: pyridoxal 5'-phosphate-dependent epilepsy

    MedlinePlus

    ... 5'-phosphate-dependent epilepsy pyridoxal 5'-phosphate-dependent epilepsy Enable Javascript to view the expand/collapse boxes. ... All Close All Description Pyridoxal 5'-phosphate-dependent epilepsy is a condition that involves seizures beginning soon ...

  14. Control of absence seizures induced by the pathways connected to SRN in corticothalamic system.

    PubMed

    Hu, Bing; Guo, Daqing; Wang, Qingyun

    2015-06-01

    The cerebral cortex, thalamus and basal ganglia together form an important network in the brain, which is closely related to several nerve diseases, such as parkinson disease, epilepsy seizure and so on. Absence seizure can be characterized by 2-4 Hz oscillatory activity, and it can be induced by abnormal interactions between the cerebral cortex and thalamus. Many experimental results have also shown that basal ganglia are a key neural structure, which closely links the corticothalamic system in the brain. Presently, we use a corticothalamic-basal ganglia model to study which pathways in corticothalamic system can induce absence seizures and how these oscillatory activities can be controlled by projections from the substantia nigra pars reticulata (SNr) to the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of the thalamus. By tuning the projection strength of the pathway "Excitatory pyramidal cortex-SRN", "SRN-Excitatory pyramidal cortex" and "SRN-TRN" respectively, different firing states including absence seizures can appear. This indicates that absence seizures can be induced by tuning the connection strength of the considered pathway. In addition, typical absence epilepsy seizure state "spike-and-slow wave discharges" can be controlled by adjusting the activation level of the SNr as the pathways SNr-SRN and SNr-TRN open independently or together. Our results emphasize the importance of basal ganglia in controlling absence seizures in the corticothalamic system, and can provide a potential idea for the clinical treatment.

  15. 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

  16. 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

  17. Differential molecular and behavioural alterations in mouse models of GABRG2 haploinsufficiency versus dominant negative mutations associated with human epilepsy.

    PubMed

    Warner, Timothy A; Shen, Wangzhen; Huang, Xuan; Liu, Zhong; Macdonald, Robert L; Kang, Jing-Qiong

    2016-08-01

    Genetic epilepsy is a common disorder with phenotypic variation, but the basis for the variation is unknown. Comparing the molecular pathophysiology of mutations in the same epilepsy gene may provide mechanistic insights into the phenotypic heterogeneity. GABRG2 is an established epilepsy gene, and mutations in it produce epilepsy syndromes with varying severities. The disease phenotype in some cases may be caused by simple loss of subunit function (functional haploinsufficiency), while others may be caused by loss-of-function plus dominant negative suppression and other cellular toxicity. Detailed molecular defects and the corresponding seizures and related comorbidities resulting from haploinsufficiency and dominant negative mutations, however, have not been compared. Here we compared two mouse models of GABRG2 loss-of-function mutations associated with epilepsy with different severities, Gabrg2(+/Q390X) knockin (KI) and Gabrg2(+/-) knockout (KO) mice. Heterozygous Gabrg2(+/Q390X) KI mice are associated with a severe epileptic encephalopathy due to a dominant negative effect of the mutation, while heterozygous Gabrg2(+/-) KO mice are associated with mild absence epilepsy due to simple haploinsufficiency. Unchanged at the transcriptional level, KI mice with severe epilepsy had neuronal accumulation of mutant γ2 subunits, reduced remaining functional wild-type subunits in dendrites and synapses, while KO mice with mild epilepsy had no intracellular accumulation of the mutant subunits and unaffected biogenesis of the remaining wild-type subunits. Consequently, KI mice with dominant negative mutations had much less wild-type receptor expression, more severe seizures and behavioural comorbidities than KO mice. This work provides insights into the pathophysiology of epilepsy syndrome heterogeneity and designing mechanism-based therapies.

  18. [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.

  19. History of neuropsychology through epilepsy eyes.

    PubMed

    Loring, David W

    2010-06-01

    In the 19th century, Hughlings Jackson relied on clinical history, seizure semiology, and the neurologic examination as methods for seizure localization to inform the first epilepsy surgeries. In the 20th century, psychological and neuropsychological tests were first employed as both diagnostic and prognostic measures. The contemporary practice of epilepsy evaluation and management includes neuropsychology as a critical component of epilepsy care and research, and epilepsy and neuropsychology have enjoyed a very special and synergistic relationship. This paper reviews how epilepsy has shaped the practice of neuropsychology as a clinical service by asking critical questions that only neuropsychologists were in a position to answer, and how clinical care of epilepsy patients has been significantly improved based on neuropsychology's unique contributions.

  20. History of Neuropsychology Through Epilepsy Eyes

    PubMed Central

    Loring, David W.

    2010-01-01

    In the 19th century, Hughlings Jackson relied on clinical history, seizure semiology, and the neurologic examination as methods for seizure localization to inform the first epilepsy surgeries. In the 20th century, psychological and neuropsychological tests were first employed as both diagnostic and prognostic measures. The contemporary practice of epilepsy evaluation and management includes neuropsychology as a critical component of epilepsy care and research, and epilepsy and neuropsychology have enjoyed a very special and synergistic relationship. This paper reviews how epilepsy has shaped the practice of neuropsychology as a clinical service by asking critical questions that only neuropsychologists were in a position to answer, and how clinical care of epilepsy patients has been significantly improved based on neuropsychology's unique contributions. PMID:20395259

  1. 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

  2. Epilepsy in sub-Saharan Africa.

    PubMed

    Prevett, Martin

    2013-02-01

    Over 10 million people in Africa have epilepsy of which most have no access to appropriate treatment. Epilepsy in Africa is different- the incidence is higher, and the causes and cultural attitudes towards it differ. This article examines the epidemiology, causes and treatment of epilepsy in sub-Saharan Africa and looks at the challenges to improve access to treatment and potential solutions and the implications for neurologists in more developed countries.

  3. Women and epilepsy in the Mediterranean cultures.

    PubMed

    Vanzan Paladin, A

    1997-08-01

    Women and epilepsy have been sharing many prejudices since the beginning of human history. Epileptic seizures have been often mistaken for hysteria and hysteria is mainly a disease of women: in the past, the physicians even proclaimed the existence of a form of epilepsy originated from the uterus. This paper briefly examines the relation women-epilepsy in the Mediterranean cultures through historical and literary examples.

  4. 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.

  5. Cortical thickness and sulcal depth: insights on development and psychopathology in paediatric epilepsy

    PubMed Central

    Siddarth, Prabha; Levitt, Jennifer; Caplan, Rochelle

    2015-01-01

    Background The relationship between cortical thickness (CThick) and sulcal depth (SDepth) changes across brain regions during development. Epilepsy youth have CThick and SDepth abnormalities and prevalent psychiatric disorders. Aims This study compared the CThick–SDepth relationship in children with focal epilepsy with typically developing children (TDC) and the role played by seizure and psychopathology variables. Method A surface-based, computational high-resolution three-dimesional (3D) magnetic resonance image analytic technique compared regional CThick–SDepth relationships in 42 participants with focal epilepsy and 46 TDC (6–16 years) imaged in a 1.5 Tesla scanner. Psychiatric interviews administered to each participant yielded psychiatric diagnoses. Parents provided seizure-related information. Results The TDC group alone demonstrated a significant negative medial fronto-orbital CThick–SDepth correlation. Focal epilepsy participants with but not without psychiatric diagnoses showed significant positive pre-central and post-central CThick–SDepth associations not found in TDC. Although the history of prolonged seizures was significantly associated with the post-central CThick–SDepth correlation, it was unrelated to the presence/absence of psychiatric diagnoses. Conclusions Abnormal CThick–SDepth pre-central and post-central associations might be a psychopathology biomarker in paediatric focal epilepsy. Declaration interest None. Copyright and usage © 2015 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703737

  6. Public awareness, understanding & attitudes toward epilepsy.

    PubMed

    Gambhir, S K; Kumar, V; Singhi, P D; Goel, R C

    1995-07-01

    The public awareness, understanding and attitudes towards epilepsy were evaluated in a north Indian population in 1992 by personal interview method. The study revealed that 92 per cent of the respondents had read or heard about epilepsy. More than 55 per cent knew someone and had seen a case of seizure. Eighty five per cent of the respondents were not aware of the cause of epilepsy or had wrong beliefs. Eighteen and 15 per cent thought epilepsy to be a hereditary disorder and a form of insanity respectively. About 40 per cent of the respondents felt that children with epilepsy should not be sent to school and also objected to their children's contact with epileptics at school or at play. Two-thirds of the respondents objected to their children marrying a person who had ever had epilepsy. Twenty per cent were ignorant about the manifestation of epilepsy and an equal number were unable to recommend any therapy in case their relatives or friends had epilepsy. Fifty seven per cent did not know what kind of first aid should be given during the epileptic attack. Although the awareness of epilepsy among Indian people was comparable to that of individuals in Western countries, the attitudes of the Indians were much more negative. Better educated people belonging to higher occupational groups were less prejudiced against social contact and schooling of their children with epileptic children compared to low educational and occupational groups.

  7. 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

  8. Metabolic treatments for intractable epilepsy.

    PubMed

    Kelley, Sarah A; Hartman, Adam L

    2011-09-01

    When a child on anticonvulsant medications continues to have seizures, what other options should be considered? Over the past 100 years, dietary therapies for the treatment of intractable epilepsy have become more widely recognized, and their use has continued to expand throughout the world. An increasing number of studies has shown efficacy of these metabolic treatments in improving seizure control. Currently, 4 types of dietary therapy are available in the clinic: the classic long chain fatty acid "ketogenic" diet, the medium chain triglyceride diet, the modified Atkins diet, and the low glycemic index treatment. These therapies should be considered earlier in the treatment of intractable epilepsy because they offer a different approach to treatment that has proven efficacious, tolerable, and cost-effective.

  9. 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

  10. [Hemiconvulsion-hemiplegia-epilepsy syndrome].

    PubMed

    Vestergaard, Maiken; Uldall, Peter

    2014-12-22

    Hemiconvulsion-hemiplegia-epilepsy syndrome is a rare consequence of a status epilepticus in the course of a febrile illness in children under the age of four years. Various degrees of hemiplegia and within a variable interval, subsequent epilepsia follows. Neuroimaging show unilateral cytotoxic oedema at the initial convulsive state, followed by severe chronic atrophy of the affected hemisphere. The aetiology remains unclear. Several mechanisms may contribute to this condition. To improve the outcome, further studies are needed and early diagnosis is essential.

  11. Assessment of Blink Reflex in Genetic Generalized Epilepsy Patients With Eyelid Myoclonia.

    PubMed

    Altıokka-Uzun, Güneş; Ekizoğlu, Esme; Kocasoy-Orhan, Elif; Bebek, Nerses; Gürses, Candan; Gökyiğit, Ayşen; Öge, Ali Emre; Baykan, Betül

    2017-03-01

    Eyelid myoclonia (EM) with or without absences are a rare type of generalized seizures associated with a variety of epilepsy syndromes with an unknown pathophysiology. The aim of this study was to investigate the possible contribution of the brainstem structures in this underrecognized special type of seizures. Sixteen consecutive patients with EM, diagnosed with genetic generalized epilepsy (GGE) according to International League Against Epilepsy 2010 criteria were included. Brainstem excitabilities were examined by blink reflex (BR) studies. The results of BR studies in GGE patients with EM were statistically compared with 2 control groups; namely age- and gender-matched healthy volunteers and juvenile myoclonic epilepsy (JME) patients without any absences and using similar antiepileptic drugs. There were no statistical differences between the thresholds of the BR studies and the BR recovery curves in terms of amplitudes and areas of healthy subjects, JME patients and GGE patients with EM. Our findings do not support a profound interictal hyperexcitability in the BR-related brainstem structures of the GGE patients with EM. It can be considered that EM may be associated with excitability changes of the occipital cortex and other cortical areas.

  12. Elevated Expression of Acid-Sensing Ion Channel 3 Inhibits Epilepsy via Activation of Interneurons.

    PubMed

    Cao, Qingqing; Wang, Wei; Gu, Juan; Jiang, Guohui; Bian, Xiling; Wang, Kewei; Xu, Zucai; Li, Jie; Chen, Guojun; Wang, Xuefeng

    2016-01-01

    Recent studies have indicated that acid-sensing ion channels may play a significant role in the termination of epilepsy. In particular, acid-sensing ion channel 3 (ASIC3) is expressed in the central nervous system and is most sensitive to extracellular pH. However, whether ASIC3 plays a role in epilepsy is unknown. In this study, qRT-PCR, Western blot, immunohistochemistry, double immunofluorescence labeling, and slice recordings were used. We first detected elevated ASIC3 expression patterns in the brains of temporal lobe epilepsy patients and epileptic rats. ASIC3 was expressed in neurons and glia in both humans and in an experimental model of epilepsy, and ASIC3 was colocalized with inhibitory GABAergic interneurons. By blocking ASIC3 with its antagonist APETx2, we observed that injected APETx2 shortened the latency to seizure and increased the incidence of generalized tonic clonic seizure compared to the control group in models of both pilocarpine- and pentylenetetrazole (PTZ)-induced seizures. Additionally, blocking ASIC3 significantly decreased the frequency of action potential (AP) firing in interneurons. Moreover, APETx2 significantly reduced the amplitudes and frequencies of miniature inhibitory postsynaptic currents (mIPSCs) while showed no differences with the APETx2 + bicuculline group and the bicuculline group. These findings suggest that elevated levels of ASIC3 may serve as an anti-epileptic mechanism via postsynaptic mechanisms in interneurons. It could represent a novel therapeutic strategy for epilepsy treatment.

  13. Epilepsy as a Neurodevelopmental Disorder

    PubMed Central

    Bozzi, Yuri; Casarosa, Simona; Caleo, Matteo

    2012-01-01

    Epilepsy is characterized by spontaneous recurrent seizures and comprises a diverse group of syndromes with different etiologies. Epileptogenesis refers to the process whereby the brain becomes epileptic and can be related to several factors, such as acquired structural brain lesions, inborn brain malformations, alterations in neuronal signaling, and defects in maturation and plasticity of neuronal networks. In this review, we will focus on alterations of brain development that lead to an hyperexcitability phenotype in adulthood, providing examples from both animal and human studies. Malformations of cortical development (including focal cortical dysplasia, lissencephaly, heterotopia, and polymicrogyria) are frequently epileptogenic and result from defects in cell proliferation in the germinal zone and/or impaired neuronal migration and differentiation. Delayed or reduced arrival of inhibitory interneurons into the cortical plate is another possible cause of epileptogenesis. GABAergic neurons are generated during early development in the ganglionic eminences, and failure to pursue migration toward the cortex alters the excitatory/inhibitory balance resulting in aberrant network hyperexcitability. More subtle defects in the developmental assembly of excitatory and inhibitory synapses are also involved in epilepsy. For example, mutations in the presynaptic proteins synapsins and SNAP-25 cause derangements of synaptic transmission and plasticity which underlie appearance of an epileptic phenotype. Finally, there is evidence that defects in synapse elimination and remodeling during early “critical periods” can trigger hyperexcitability later in life. Further clarification of the developmental pathways to epilepsy has important implications for disease prevention and therapy. PMID:22457654

  14. Excessive masturbation after epilepsy surgery.

    PubMed

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

    2004-02-01

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

  15. 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

  16. Understanding Death in Children With Epilepsy.

    PubMed

    Donner, Elizabeth J; Camfield, Peter; Brooks, Linda; Buchhalter, Jeffrey; Camfield, Carol; Loddenkemper, Tobias; Wirrell, Elaine

    2017-01-31

    Death in children with epilepsy is profoundly disturbing, with lasting effects on the family, community, and health care providers. The overall risk of death for children with epilepsy is about ten times that of the general population. However, the risk of premature death for children without associated neurological comorbidities is similar to that of the general population, and most deaths are related to the cause of the epilepsy or associated neurologic disability, not seizures. The most common cause of seizure-related death in children with epilepsy is sudden unexpected death in epilepsy (SUDEP). SUDEP is relatively uncommon in childhood, but the risk increases if epilepsy persists into adulthood. Although the direct cause of SUDEP remains unknown, most often death follows a generalized convulsive seizure and the risk of SUDEP is strongly related to drug-resistant epilepsy and frequent generalized tonic-clonic seizures. The most effective SUDEP prevention strategy is to reduce the frequency of seizures, although a number of seizure detection devices are under development and in the future may prove to be useful for seizure detection for those at particularly high risk. There are distinct benefits for health care professionals to discuss mortality with the family soon after the diagnosis of epilepsy. An individual approach is appropriate. When a child with epilepsy dies, particularly if the death was unexpected, family grief may be profound. Physicians and other health care professionals have a critical role in supporting families that lose a child to epilepsy. This review will provide health care providers with information needed to discuss the risk of death in children with epilepsy and support families following a loss.

  17. Altered hippocampal myelinated fiber integrity in a lithium-pilocarpine model of temporal lobe epilepsy: a histopathological and stereological investigation.

    PubMed

    Ye, Yuanzhen; Xiong, Jiajia; Hu, Jun; Kong, Min; Cheng, Li; Chen, Hengsheng; Li, Tingsong; Jiang, Li

    2013-07-19

    The damage of white matter, primarily myelinated fibers, in the central nervous system (CNS) of temporal lobe epilepsy (TLE) patients has been recently reported. However, limited data exist addressing the types of changes that occur to myelinated fibers inside the hippocampus as a result of TLE. The current study was designed to examine this issue in a lithium-pilocarpine rat model. Investigated by electroencephalography (EEG), Gallyas silver staining, immunohistochemistry, western blotting, transmission electron microscopy, and stereological methods, the results showed that hippocampal myelinated fibers of the epilepsy group were degenerated with significantly less myelin basic protein (MBP) expression relative to those of control group rats. Stereological analysis revealed that the total volumes of hippocampal formation, myelinated fibers, and myelin sheaths in the hippocampus of epilepsy group rats were decreased by 20.43%, 49.16%, and 52.60%, respectively. In addition, epilepsy group rats showed significantly greater mean diameters of myelinated fibers and axons, whereas the mean thickness of myelin sheaths was less, especially for small axons with diameters from 0.1 to 0.8µm, compared to control group rats. Finally, the total length of the myelinated fibers in the hippocampus of epilepsy group rats was significantly decreased by 56.92%, compared to that of the control group, with the decreased length most prominent for myelinated fibers with diameters from 0.4 to 0.8µm. This study is the first to provide experimental evidence that the integrity of hippocampal myelinated fibers is negatively affected by inducing epileptic seizures with pilocarpine, which may contribute to the abnormal propagation of epileptic discharge.

  18. Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies?

    PubMed

    Noureldine, M H A; Harifi, G; Berjawi, A; Haydar, A A; Nader, M; Elnawar, R; Sweid, A; Al Saleh, J; Khamashta, M A; Uthman, I

    2016-11-01

    Epilepsy and seizures are reported among the neurological manifestations of antiphospholipid syndrome (APS) at a prevalence rate of approximately 8%, which is nearly 10 times the prevalence of epilepsy in the general population. The association of seizures with antiphospholipid antibodies (aPL) is even more significant in the presence of systemic lupus erythematosus (SLE). In this review, we discuss the epidemiological, pathophysiological, laboratory, clinical, and radiological aspects of this association, and derive suggestions on when to consider testing for aPL in epileptic patients and how to manage seizures secondary to APS based on literature data. Epilepsy due to APS should be considered in young patients presenting with seizures of unknown origin. Temporal lobe epilepsy seems to be particularly prevalent in APS patients. The pathogenesis is complex and may not only involve micro-thrombosis, but also a possible immune-mediated neuronal damage. Patients with seizures and positive aPL tend to develop thrombocytopenia and livedo racemosa more frequently compared with those without aPL. Magnetic resonance imaging (MRI) remains the imaging modality of choice in these patients. The presence of SLE and the presence of neurological symptoms significantly correlate with the presence of white matter changes on MRI. In contrast, the correlation between aPL positivity and the presence of white matter changes is very weak. Furthermore, MRI can be normal in more than 30-40% of neuropsychiatric lupus patients with or without aPL. aPL testing is recommended in young patients presenting with atypical seizures and multiple hyper-intensity lesions on brain MRI in the absence of other possible conditions. New MRI techniques can better understand the pathology of brain damage in neuro-APS. The therapeutic management of epileptic APS patients relies on anti-epileptic treatment and anticoagulant agents when there is evidence of a thrombotic event. In the absence of consensual

  19. 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.

  20. FORCED NORMALIZATION: Epilepsy and Psychosis Interaction

    PubMed Central

    Loganathan, Muruga A.; Enja, Manasa

    2015-01-01

    Forced normalization is the emergence of psychoses following the establishment of seizure control in an uncontrolled epilepsy patient. Two illustrative clinical vignettes are provided about people with epilepsy that was newly controlled and followed by emergence of a psychosis; symptoms appeared only after attaining ictal control. For recognition and differential diagnosis purposes, understanding forced normalization is important in clinical practice. PMID:26155377

  1. 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…

  2. 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.

  3. Stem cell therapy for treatment of epilepsy.

    PubMed

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

    2014-01-01

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

  4. 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…

  5. 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…

  6. 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…

  7. Febrile Seizures and Epilepsy: Possible Outcomes

    MedlinePlus

    ... Childhood Epilepsy (PACE) practice guideline for the long-term management of the http://www.paceusa.org child with ... on Quality Improvement and tensen J. The long-term risk of epilepsy after febrile seizures in Management SboFSAAoP. Febrile seizures: clinical susceptible subgroups. Am J ...

  8. 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

  9. 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.

  10. Video electroencephalogram telemetry in temporal lobe epilepsy

    PubMed Central

    Mani, Jayanti

    2014-01-01

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

  11. Social competence of preschool children with epilepsy.

    PubMed

    Rantanen, K; Timonen, S; Hagström, K; Hämäläinen, P; Eriksson, K; Nieminen, P

    2009-02-01

    The aims of this study were to describe the social competence of 3- to 6-year-old children with epilepsy (n=26) compared with that of age- and gender-matched healthy controls (n=26). Social competence was assessed with the Vineland Social Maturity Scale, Conners' Parent Rating Scales-Revised, and the Child Behavior Checklist. The results indicate that the children with epilepsy, especially with complicated epilepsy, had fewer age-appropriate social skills and more attention and behavior problems than the healthy children, as reported by parents. It is possible that the lack of age-appropriate social skills and the presence of attention problems predispose to behavioral problems. Also, epilepsy-related factors impaired the achievement of social competence. This study shows that the preschool children with complicated, early-onset epilepsy are at increased risk of difficulties in social competence.

  12. Epilepsy during pregnancy: focus on management strategies

    PubMed Central

    Borgelt, Laura M; Hart, Felecia M; Bainbridge, Jacquelyn L

    2016-01-01

    In the US, more than one million women with epilepsy are of childbearing age and have over 20,000 babies each year. Patients with epilepsy who become pregnant are at risk of complications, including changes in seizure frequency, maternal morbidity and mortality, and congenital anomalies due to antiepileptic drug exposure. Appropriate management of epilepsy during pregnancy may involve frequent monitoring of antiepileptic drug serum concentrations, potential preconception switching of antiepileptic medications, making dose adjustments, minimizing peak drug concentration with more frequent dosing, and avoiding potentially teratogenic medications. Ideally, preconception planning will be done to minimize risks to both the mother and fetus during pregnancy. It is important to recognize benefits and risks of current and emerging therapies, especially with revised pregnancy labeling in prescription drug product information. This review will outline risks for epilepsy during pregnancy, review various recommendations from leading organizations, and provide an evidence-based approach for managing patients with epilepsy before, during, and after pregnancy. PMID:27703396

  13. Supplementation of a maternal low-protein diet in rat pregnancy with folic acid ameliorates programming effects upon feeding behaviour in the absence of disturbances to the methionine-homocysteine cycle.

    PubMed

    Engeham, Sarah F; Haase, Andrea; Langley-Evans, Simon C

    2010-04-01

    Maternal protein restriction in rat pregnancy is associated with altered feeding behaviour in later life. When allowed to self-select their diet, rats subject to prenatal undernutrition show an increased preference for fatty foods. The main aim of the present study was to evaluate the contribution of folic acid in the maternal diet to programming of appetite, since disturbances of the folate and methionine-homocysteine cycles have been suggested to impact upon epigenetic regulation of gene expression and hence programme long-term physiology and metabolism. Pregnant rats were fed diets containing either 9 or 18 % casein by weight, with folate provided at either 1 or 5 mg/kg diet. Adult male animals exposed to low protein (LP) in fetal life exhibited increased preference for high-fat food. Providing the higher level of folate in the maternal diet prevented this effect of LP, but offspring of rats fed 18 % casein diet with additional folate behaved in a similar manner to LP-exposed animals. Among day 20 gestation fetuses, it was apparent that both protein restriction and maternal folate supplementation could have adverse effects upon placental growth. Examination of methionine-homocysteine and folate cycle intermediates, tissue glutathione concentrations and expression of mRNA for methionine synthase, DNA methyltransferase 1 and methyltetrahydrofolate reductase revealed no gross disturbances of folate and one-carbon metabolism in either maternal or fetal tissue. The present findings indicated that any role for DNA methylation in programming of physiology is not related to major perturbations of folate metabolism, and is likely to be gene-specific rather than genome-wide.

  14. Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4-week comprehensive toxicity study using F344 gpt delta rats.

    PubMed

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Horibata, Katsuyoshi; Ishii, Yuji; Umemura, Takashi; Honma, Masamitsu; Nohmi, Takehiko; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-07-01

    3-Monochloropropane-1,2-diol (3-MCPD) is regarded as a rat renal and testicular carcinogen and has been classified as a possible human carcinogen (group 2B) by International Agency for Research on Cancer. This is potentially of great importance given that esters of this compound have recently found to be generated in many foods and food ingredients as a result of food processing. There have been a few reports about their toxicity, although we have recently found that the toxicity profile of 3-MCPD esters was similar to that of 3-MCPD in a rat 13-week repeated dose study, except for the acute renal toxicity seen in 3-MCPD-treated females. In the present study, to examine in vivo genotoxicity we administered equimolar doses of 3-MCPD or 3-MCPD fatty acid esters (palmitate diester, palmitate monoester and oleate diester) to 6-week-old male F344 gpt delta rats carrying a reporter transgene for 4 weeks by intragastric administration. In vivo micronucleus, Pig-a mutation and gpt assays were performed, as well as investigations of major toxicological parameters including histopathological features. As one result, the relative kidney weights of the 3-MCPD and all three ester groups were significantly increased compared with the vehicle control group. However, the frequency of micronucleated reticulocytes and Pig-a mutant red blood cells did not differ among groups. Moreover, no changes were observed in mutant frequencies of gpt and red/gam (Spi(-)) genes in the kidney and the testis of 3-MCPD and 3-MCPD-fatty-acid-esters-treated rats. In histopathological analyses, no treatment related changes were observed, except for decrease of eosinophilic bodies in the kidneys of all treated groups. These results suggest that 3-MCPD and its fatty acid esters are not in vivo genotoxins, although they may exert renal toxicity.

  15. When Should Genetic Testing Be Performed in Epilepsy Patients?

    PubMed Central

    2017-01-01

    This review is a summary of a talk presented at the 2015 American Epilepsy Society Annual Meeting. Its purposes are 1) to review developments in epilepsy genetics, 2) to discuss which groups of patients with epilepsy might benefit from genetic testing, and 3) to present a rational approach to genetic testing in epilepsy in the rapidly evolving era of genomic medicine. PMID:28331464

  16. 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

  17. Medicosocial aspect of people with epilepsy in Japan--a survey from standpoint of epilepsy center.

    PubMed

    Higashi, T; Ishihara, O; Wada, T

    1979-01-01

    Medicosocial aspects of 2,000 patients with epilepsy were outlined on the basis of international classification of epilepsies and epileptic seizures. 1. The incidence of secondary generalized epilepsy was higher compared with that reported previously. It was possible that we have been dealing with rather intractable epilepsy. Non-convulsive epileptic seizures should be treated as intensively as convulsive attacks. 2. Contrary to primary generalized epilepsy, secondary generalized epilepsy and partial epilepsy, a part of which was complex partial seizures, were more prone to be associated with psychological difficulties. 3. The rate of normal mentality was apparently proportional to the actual ease of employment among adult patients. Fortunately, the general attitude of education toward younger people with epilepsy was seemingly generous. However, the marital status of both sexes was far from satisfactory. The stigma might have been felt more by adult patients than younger ones. 4. It appeared to be conceivable that two-thirds of the people with epilepsy are treatable to a certain extent by adequate regimens while one-tenth are obliged to stay in residential centers for a lengthy period of time. Thus, various rehabilitation activities are indicated for one-fourth of the patient population. Actual strategy for rehabilitation of epileptics should be individually designed in accordance with the natural history of each epilepsy.

  18. Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

    PubMed

    Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F

    2010-11-01

    Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be

  19. Spotlight on levetiracetam in epilepsy.

    PubMed

    Lyseng-Williamson, Katherine A

    2011-10-01

    Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial-onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial-onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial-onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial-onset seizures. Levetiracetam also provided seizure control relative to placebo as

  20. Cardiovascular manifestations of autonomic epilepsy.

    PubMed

    Freeman, Roy

    2006-02-01

    Cardiovascular autonomic manifestations of seizures occur frequently in the epileptic population. Common manifestations include alterations in heart rate and rhythm, blood pressure, ECG changes and chest pain. The neuroanatomical and neurophysiological underpinnings of these autonomic manifestations are not been fully elucidated. Diagnostic confusion may arise when ictal symptoms are confined to the autonomic nervous system; conversely, such symptoms in association with convulsions or altered consciousness are more readily recognized as concomitant ictal features. Awareness of the diverse autonomic manifestations of epilepsy will enhance diagnosis and lead to more effective therapy of these patients.

  1. The social competence and behavioral problem substrate of new- and recent-onset childhood epilepsy.

    PubMed

    Almane, Dace; Jones, Jana E; Jackson, Daren C; Seidenberg, Michael; Hermann, Bruce P

    2014-02-01

    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).

  2. 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.

  3. Callosal agenesis, chorioretinal lacunae, absence of infantile spasms, and normal development: Aicardi syndrome without epilepsy?

    PubMed

    Prats Viñas, Jose Maria; Martinez Gonzalez, María Jesús; Garcia Ribes, Ainhoa; Martinez Gonzalez, Sonia; Martinez Fernandez, Ricardo

    2005-06-01

    Aicardi syndrome is defined by the clinical triad of infantile spasms, agenesis of the corpus callosum, and pathognomonic chorioretinal lacunae. Almost all patients are females with severe cognitive and physical disabilities. All of the cases reported in the literature have had early-onset seizures. Most cases of Aicardi syndrome exhibit very slow development, even when seizures are eventually controlled, and the cases with a relatively favourable outcome are associated with low intelligence quotient levels. A relationship between chorioretinal changes or severity of the agenesis of the corpus callosum and prognosis of Aicardi syndrome has been claimed, but few data are available about the clinical features that can predict clinical outcome. We describe a case of Aicardi syndrome in a female aged 24 months. Magnetic resonance imaging showed complete agenesis of the corpus callosum and ophthalmoscopy revealed chorioretinal lacunae in the left eye. She had never had seizures and her psychomotor and language development were normal for age.

  4. Temporal plus epilepsy: Anatomo-electroclinical subtypes

    PubMed Central

    Andrade-Machado, René; Benjumea-Cuartas, Vanessa

    2016-01-01

    Background: Mesial temporal lobe epilepsy (TLE) is a remediable epileptic syndrome. About 40% of patients continue to have seizures after standard temporal lobectomy. It has been suggested that some of these patients could actually suffer from a more complex epileptogenic network. Because a few papers have been dedicated to this topic, we decided to write an article updating this theme. Methods: We performed a literature search using the following terminology: “temporal plus epilepsy and networks,” “temporal plus epilepsy,” “orbito-temporal epilepsy,” “temporo-insular epilepsy,” “temporo-parieto-occipital (TPO) epilepsy,” “parieto-temporal epilepsy,” “intracortical evoked potential and temporal plus epilepsy,” “temporal lobe connectivity and epilepsy,” “intracortical evoked potential and epilepsy surgery,” “role of extratemporal structures in TLE,” “surgical failure after temporal lobectomy,” “Diffusion tensor imaging (DTI) and temporal epilepsy,” and “positron emission tomography (PET) in temporal plus lobe epilepsy” in the existing PubMed databases. We searched only English and Spanish literature. Only papers that fit with the above-mentioned descriptors were included as part of the evidence. Other articles were used to reference some aspects of the temporal plus epilepsy. Results: A total of 48 papers from 2334 were revised. The most frequently reported auras in these groups of patients are gustatory hallucinations, vestibular illusions, laryngeal and throat constriction, atypical distribution of somatosensory symptoms (perioral and hands, bilaterally hands paresthesias, trunk and other). The most common signs are tonic posturing, hemifacial twist, and frequent bilateral clonic movements. Interictal electroencephalographic (EEG) patterns exhibit regional and frequently bilateral spikes and/or slow waves. The first ictal electrographic change is mostly regional. It is important to note that the evidence is

  5. 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

  6. Congenital Absence of the Pericardium

    PubMed Central

    Kim, Hyun-Jin; Cho, Goo-Yeong; Choi, Sang Il

    2014-01-01

    Congenital absence of the pericardium is a rare cardiac malformation and is most often asymptomatic. It is usually discovered as an incidental finding. Physical examination, chest radiography, and electrocardiogram are often unremarkable. Echocardiography provides valuable information, and sometimes computed tomography or magnetic resonance imaging is needed for subsequent confirmation. PMID:24753808

  7. 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

  8. Study on expression of laminin in patients with intractable epilepsy.

    PubMed

    Wu, Yuan; Feng, Yun; Pang, Jia-Rong; Tang, Mei; Liu, Xiu-Ying; Li, Jia-Quan; Wang, Xue-Feng

    2009-01-01

    In this study, we examined differences in serum laminin expression in patients with intractable epilepsy. Our results suggest that elevated laminin may contribute to the pathogenesis of intractable epilepsy. ELISA and western blots were used to measure laminin in the serum of 30 intractable epilepsy patients, 46 nonintractable epilepsy patients, and 20 normal subjects. By ELISA, serum laminin levels were greater in intractable epilepsy patients (177.396 +/- 30.602) and nonintractable epilepsy patients (121.915 +/- 35.215) than in normal control subjects (67.474 +/- 7.197); laminin was significantly greater in the intractable epilepsy group than in the nonintractable epilepsy group. In western blots, the optical density ratio of laminin to ss-actin was 0.871 +/- 0.032 for the intractable epilepsy group, 0.686 +/- 0.017 for the nonintractable epilepsy group, and 0.385 +/- 0.024 for the normal control group. The optical density ratios of the intractable and nonintractable epilepsy groups were higher than those for the normal control group, and the intractable epilepsy group was even greater than the nonintractable epilepsy group. Thus, l