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PubMed1991

Usefulness of the newly proposed International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders (1989): a trial on adult patients in a neuropsychiatric clinic.

The utility of the "International Classification of Epilepsies, Epileptic Syndromes, and Related Seizure Disorders," proposed by ILAE in 1989, was investigated in a neuropsychiatric clinic with a patient population numbering 300. Two hundred and three patients (67.7%) had localization-related epilepsies (LRE), including one idiopathic case. Sixty-six patients (22%) had generalized epilepsies, 50 idiopathic, 2 Lennox-Gastaut syndrome, and 14 symptomatic. Thirty-one patients (10.3%) with generalized tonic-clonic seizures occurring only during sleep had the epilepsies undetermined whether they are focal or generalized. In the symptomatic LRE cases, 34 cases could not be classified, and 7 of the cases with frontal lobe epilepsies were difficult to subtype. Eleven of the symptomatic LRE cases had some independent seizures, multiple foci in surface EEGs and were intractable. These cases may be defined as "multifocal epilepsies."

Adult↗

PubMed1999

[Rational choice of antiepileptic treatment].

The choice of the adequate antiepileptic treatment is based on the clinical experience more than rationality. During some decades, the combination of two antiepileptic drugs was considered the initial treatment but monotherapy showed more advantages (effectiveness, fewer adverse events, fewer teratogenic effects and better compliance). New antiepileptic drugs have increased our interest and knowledge of the epilepsies. They have changed some of our therapeutical schemes. Sodium valproate continues to be considered the choice treatment for all the idiopathic, cryptogenic and symptomatic generalized epilepsies. Lamotrigine and topiramate are two valid alternatives in these epileptic syndromes. In West's syndrome vigabatrin is considered the initial treatment. Carbamacepine, vigabatrine and tiagabine are not indicated in the treatment of generalized idiopathic epilepsies especially in patients with absence seizures. In focal epilepsies, both cryptogenic and symptomatic all the antiepileptic drugs have shown efficacy and the choice treatment is based on the adverse events and the teratogenic power. Prospective studies in patients with the same type of seizures and epileptic syndromes will allow us to determine the more adequate antiepileptic treatment.

Anticonvulsants↗

PubMed1995

[Juvenile myoclonic epilepsy].

Juvenile myoclonic epilepsy (JME) is an idiopathic primary generalized epilepsy of teenagers, characterized by massive myoclonic seizures. 18 patients were investigated. Myoclonic seizures first appeared at the mean age of 14 years and were characterized by short rapid abrupt involuntary jerks of extremities with the preserved consciousness. There were 2 types of myoclonic fits: massive seizures with symmetric jerks of extremities (33% of patients) and asymmetric asynchronous seizures of various frequency and intensity (67% of patients). In 50% of patients there were myoclonic seizures in leg muscles, in some cases patients fell down (myoclonic-astatic seizures). The authors emphasize the unusually high frequency of cases with myoclonic seizures combined with absences (66,7%) and generalized convulsions (83,3%) occurring on awakening. It is suggested that myoclonic component in the structure of absences may be an early sign of JME and predict development of myoclonic seizures.

Adolescent↗

PubMed2003

Age at focal epilepsy onset varies by sex and hemispheric lateralization.

BACKGROUND: Previous studies have shown that interictal epileptiform discharges favor the left hemisphere in adults but the right side in children up until age 5. This may be due to sex-influenced asymmetric brain maturation. To clarify this relationship, the authors analyzed age at epilepsy onset by sex and by lateralization of epileptiform activity. METHODS: An adult epilepsy center long-term monitoring database was used to define patients with exclusively unilateral epileptiform findings. Three groups were studied: any epileptiform activity (n = 404), ictal activity (n = 287), and interictal activity (n = 265). The second and third groups were drawn from the first group and the second and third groups overlapped with each other. Side of lateralized finding and sex were analyzed via factorial two-way analysis of variance with the outcome variable being age at epilepsy onset. Comparison analysis included patients with generalized epilepsy (n = 114), nonepileptic seizures (NES, n = 232), and surgical mesial temporal sclerosis (MTS, n = 116). RESULTS: Patients with unilateral epileptiform activity displayed bimodal epilepsy onset ages with infant and adolescent peaks. For patients with a right-sided focus, epilepsy onset was earlier in men (14.4 years) than women (20.7 years). In contrast, among patients with a left-sided focus, epilepsy began earlier in women (18.2 years) than men (19.9 years, p < 0.01). Parallel results were found in unilateral ictal (p < 0.01) and unilateral interictal activity (p = 0.01). Patients with surgical MTS, NES, or generalized seizure showed no similar patterns. CONCLUSIONS: In adult patients with focal epilepsy, sex and lateralized epileptiform abnormalities may be related to age at epilepsy onset.

Adolescent↗

PubMed2004

Ictal and interictal perfusion variations measured by SISCOM analysis in typical childhood absence seizures.

Single photon emission computed tomography (SPECT) is currently used in the presurgical evaluation of medically intractable partial epilepsies, but not very often, in generalized epilepsy. In the present study, we used the SISCOM procedure, which represents the fusion of MRI and ictal-interictal difference SPECT images using (99m)Tc-ECD, to study cerebral blood flow changes during the ictal and postictal phases of typical childhood absence seizures. The study was performed on four children with typical, difficult to treat absence seizures, aged 10-13 years at the time of scan. The delay between the onset of absence seizures and the injection of (99m)Tc-ECD was carefully noted. One scan was performed during the ictal phase and showed diffuse blood flow decreases, while the three other scans performed during the postictal phase, showed generalized blood flow increase. These data are consistent with most previous data reporting generalized changes in functional activity, not limited to the thalamo-cortical circuit in which absence seizures originate, and a decrease in cerebral blood flow during the ictal phase. Our data are concordant with the hypothesis that neuronal activity underlying the occurrence of spike-and-wave discharges does not seem to require an increase in metabolic demand and blood flow rates. [Published with videosequences].

Adolescent↗

PubMed2004

A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction.

A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel alpha subunit. The mutation decreased modulation of the alpha subunit by beta1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of beta1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type alpha subunit with the beta1 or beta3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for beta subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the alpha and beta1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility.

Action Potentials↗

PubMed1998

JH8, a gene highly homologous to the mouse jerky gene, maps to the region for childhood absence epilepsy on 8q24.

Insertional inactivation of the jerky gene in transgenic mice resulted epileptic seizures, suggesting that the jerky gene was responsible for mouse epilepsy. To isolate a human homologue of the jerky gene, we screened an Expressed Sequence Tag (EST) database using the cDNA sequence of the mouse jerky gene and identified several EST clones which contained homologous sequences to mouse jerky gene. Using a clone which showed highest homology as a probe, we isolated cDNA clones from a human fetal brain cDNA library. Sequence analysis of these clones named JH8 (jerky homologue of Human on chromosome 8) indicated that it encoded a putative protein with 520 amino acid residues. The JH8 gene has 77% identity to the mouse jerky gene at the DNA level, and its protein has 76% identity and 84% similarity to the mouse protein at the amino acid level. Northern blot analysis showed that the JH8 gene is expressed ubiquitously with a major transcript of about 9.5 kb in size. Fluorescence in situ Hybridization (FISH) analysis and radiation hybrid panel mapping revealed that the JH8 gene was located on chromosome band 8q24.3 in a region that was syntenic to mouse chromosome 15, the mapping site of the mouse jerky gene. Childhood Absence Epilepsy (CAE), one type of Idiopathic Generalized Epilepsy (IGE), has been mapped to chromosome 8q24.3 by linkage analysis. These results suggest that JH8 is a strong candidate gene for CAE.

Animals↗

PubMed2006

Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy.

Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy with febrile seizures plus. This study reports the identification of six de novo SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including a tetranucleotide deletion in exon 26. The same deletion was previously observed in two unrelated patients and appears to result from slipped-strand mispairing of a direct repeat during deoxyribonucleic acid replication. Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides.

Adolescent↗

PubMed2003

Mechanisms of depression in epilepsy from a clinical perspective.

The epilepsies are a complex group of disorders commonly associated with brain dysfunction, social isolation, and vocational difficulty. Each of these factors may contribute to increased prevalence of depressive disorders in epilepsy, but the specific mechanisms are not completely understood. The brain regions commonly involved in various types of epilepsies, such as the hippocampus and amygdala in temporal lobe epilepsy and subcortical nuclei in idiopathic generalized epilepsies, are important components of current models of depression. Increased understanding of mechanisms of depression in epilepsy is not only crucial for improving care of many persons with seizures, but may also yield useful information about principal mechanisms underlying both depression and epileptogenesis.

Brain↗

PubMed2003

T-type calcium channel gene alpha (1G) is not associated with childhood absence epilepsy in the Chinese Han population.

We investigated whether the T-type calcium channel gene alpha (1G) is associated with childhood absence epilepsy (CAE), a form of idiopathic generalized epilepsy. We carried out direct sequencing of exons 1-37 and the exon-intron boundaries of the alpha (1G) gene in 48 Han Chinese patients with CAE and 48 normal controls. We found no mutation in the exons of alpha (1G). However, we did identify six single nucleotide polymorphisms (SNPs). Using two of these as markers, we carried out a case-control study in 192 patients with CAE and 192 normal controls. The allele and genotype distributions of all the SNPs studied were not significantly different between cases and control groups, thus the alpha (1G) gene is not an important susceptibility gene for CAE, at least in the Chinese population.

Alleles↗

PubMed1989

[Contribution of ambulatory EEG recording (Medilog 9000) in a population of epileptics].

Thirty-four epileptic patients, aged 9 to 36, were submitted to A/EEG between May 1987 and July 1988. All patients had a thorough clinical and EEG work-up including long-term conventional EEG, afternoon polygraphic sleep recording and, in some cases, full-night EEG and video monitoring. Patients were divided into 2 groups: group I included 19 patients (18 with symptomatic partial epilepsy (SPE) and 1 with idiopathic generalized epilepsy (IGE) in whom no seizure had ever been recorded in spite of EEG recordings averaging a total of 16 hrs 10 min, awake and asleep); group II included 15 subjects (6 with SPE, 5 with IGE, 3 with symptomatic GE and 1 with undetermined epilepsy) in whom one or several seizures had been recorded. A/EEG was performed in order to: 1) obtain better clinical and EEG characterization of seizures, 2) study the circadian distribution of seizures, 3) verify the efficacy of drug treatment and, 4) establish the epileptic or non-epileptic nature of some ictal events. The results of A/EEG were considered positive in 52.63% of group I patients and in 93.33% of group II patients. The authors discuss the specific advantages of A/EEG vs conventional EEG: recording of seizures with random occurrence, of seizures accompanied by falls, checking the remission of seizures.

Adolescent↗

PubMed2002

Epileptic syndromes in childhood: clinical features, outcomes, and treatment.

We reviewed the clinical features, outcome, and treatment of many of the epileptic syndromes that begin in the childhood from 2 to 12 years of age, using a review of the literature and personal experience, with most references to authoritative texts. The developmental tasks of childhood are centered on refinement of motor skills and development of complex intellectual and social skills. The childhood onset epilepsies can be divided into benign, intermediate, and catastrophic based on their impact on childhood development. The clearest benign epilepsy is benign rolandic epilepsy, which often does not require medication treatment. The definition of benign occipital epilepsy is still often vague. In the intermediate category, childhood absence epilepsy often has associated learning disorders and a poor social outcome. About 50% of children with cryptogenic partial seizures have a very benign course, even though their epilepsy syndrome is not well defined. Generalized epilepsy with febrile seizures plus (GEFS+) has a dominant inheritance with a defined defect in cerebral sodium channels, but varies considerably in severity within affected members of the same kindred. The catastrophic epilepsies in childhood all have an inconsistent response to AED treatment and include continuous spike-wave in slow sleep (with variable severity), Landau-Kleffner syndrome (with a confusing overlap with autistic regression), the Lennox Gastaut syndrome (with broad defining features), and myoclonic-astatic epilepsy (with important overlaps with Lennox-Gastaut). Many of the epilepsies that begin in childhood are benign. Others interfere seriously with cognitive and social development.

Adolescent↗

PubMed2004

Gating effects of mutations in the Cav3.2 T-type calcium channel associated with childhood absence epilepsy.

Childhood absence epilepsy (CAE) is a type of generalized epilepsy observed in 2-10% of epileptic children. In a recent study by Chen et al. (Chen, Y., Lu, J., Pan, H., Zhang, Y., Wu, H., Xu, K., Liu, X., Jiang, Y., Bao, X., Yao, Z., Ding, K., Lo, W. H., Qiang, B., Chan, P., Shen, Y., and Wu, X. (2003) Ann. Neurol. 54, 239-243) 12 missense mutations were identified in the CACNA1H (Ca(v)3.2) gene in 14 of 118 patients with CAE but not in 230 control individuals. We have functionally characterized five of these mutations (F161L, E282K, C456S, V831M, and D1463N) using rat Ca(v)3.2 and whole-cell patch clamp recordings in transfected HEK293 cells. Two of the mutations, F161L and E282K, mediated an approximately 10-mV hyperpolarizing shift in the half-activation potential. Mutation V831M caused a approximately 50% slowing of inactivation relative to control and shifted half-inactivation potential approximately 10 mV toward more depolarized potentials. Mean time to peak was significantly increased by mutation V831M but was unchanged for all others. No resolvable changes in the parameters of the IV relation or current kinetics were observed with the remaining mutations. The findings suggest that several of the Ca(v)3.2 mutants allow for greater calcium influx during physiological activation and in the case of F161L and E282K can result in channel openings at more hyperpolarized (close to resting) potentials. This may underlie the propensity for seizures in patients with CAE.

Animals↗

PubMed1996

Does naming contribute to memory self-report in temporal lobe epilepsy?

The present study evaluated the hypothesis (Mayeux et al., 1980) that visual confrontation naming deficits may underlie the memory complaint in patients with temporal lobe epilepsy (TLE). Thirty-nine patients with medically refractory left (n = 23) and right (n = 16) TLE were compared with an epilepsy control group with idiopathic primary generalized epilepsy (n = 38). All subjects completed selected subtests of the Multilingual Aphasia Examination and Wechsler Memory Scale (Form 1) together with a measure specifically designed for quantification of the memory complaint in TLE. Objective verbal memory test performance, confrontation naming, repetition, and comprehension were unrelated to memory self-report. Controlled Oral Word Association was the only measure to exert an influence on memory self-ratings, and this relationship was specific to the TLE group. The hypothesis of Mayeux et al. (1980) was not specifically supported, but the present findings do suggest that cognitive processes reflected in orthographically based and internally generated word retrieval play a role in memory self-report.

Adult↗

PubMedDate not supplied

Landau-Kleffner syndrome: a pharmacologic study of five cases.

Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae.

Adrenal Cortex Hormones↗

PubMed1996

Self-reported sexual function and sexual arousability in women with epilepsy.

PURPOSE: Women with epilepsy are at risk for sexual dysfunction but the frequency and types of dysfunction have not been well characterized. METHODS: Self-reported sexual function was evaluated in 116 women aged 18-65 years with epilepsy and no concomitant medical or psychiatric illness, including 99 with localization-related epilepsy (LRE) and 17 with primary generalized epilepsy (PGE). Variables evaluated included seizure frequency, age of seizure onset, and antiepileptic drug (AED) exposure. Standardized inventories assessed sexual functioning, sexual arousability and anxiety, sexual behavior, and depression. RESULTS: Although sexual experience was not reduced, women with PGE and LRE reported significantly less sexual arousability and women with LRE reported significantly more sexual anxiety. Women with LRE experienced significantly more dyspareunia, vaginismus, arousal insufficiency, and sexual dissatisfaction, whereas women with PGE experienced anorgasmia and sexual dissatisfaction. Sexual symptoms were not associated with seizure frequency, AED exposure, sexual experience, depression, or prepubertal seizure onset. CONCLUSIONS: In contrast to subjects of previous research, the women in our study did not have a disorder of sexual desire, but more than one third experienced disorders of sexual arousal, implying a physiological deficit. Although the etiology for these arousal phase dysfunctions has not been defined, such conditions are treatable and warrant referral to a gynecologist versed in the treatment of sexual disorders.

Adolescent↗

PubMed2006

Identification of a novel locus for febrile seizures and epilepsy on chromosome 21q22.

PURPOSE: To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy. BACKGROUND: AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile seizures plus (GEFS+), is characterized by heterogeneous phenotypes including FS persisting beyond the usual age of remission or coexisting with afebrile seizures. Mutations in three subunits of sodium channel genes and one GABA(A)-receptor subunit gene have been identified in some GEFS+ pedigrees. Six genetic loci for FS have been reported so far, but the molecular basis of FS remains unknown. METHODS: We identified a five-generation family with 13 individuals affected by FS. Evidence was found for coexisting afebrile seizures in some affected individuals. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. After excluding previously identified loci associated with FS and epilepsy, a genome-wide search was performed. RESULTS: Two affected individuals reported only a single FS, whereas the other affected individuals had a history of repeated FS. Coexisting afebrile seizures developed in three individuals. The mode of inheritance was consistent with AD inheritance with an incomplete penetrance. Tight linkage to a group of markers on chromosome 21q22 was identified with flanking markers D21S1909 and D21S1444, and maximum 2-point lod score 3.35 for markers D21S1910 and D21S1894. We excluded four ion-channel genes within this 6.5-cM locus as a cause of FS and epilepsy in this family. CONCLUSIONS: We report a novel locus on chromosome 21q22 for AD FS. Identification of the gene causing epilepsy on chromosome 21q22 will advance our understanding of inherited epilepsy and FS, and possibly other types of epilepsies.

Adult↗

PubMed2006

A long-term follow-up of zonisamide monotherapy.

OBJECTIVES: Several studies have reported the safety and efficacy of zonisamide monotherapy, but studies on its long-term outcomes are limited. This chart review was conducted to evaluate the long-term outcomes of zonisamide monotherapy. METHODS: The charts were reviewed for 77 patients treated with zonisamide as monotherapy for 6-180 months between May 1985 and December 2003. Outcomes were analyzed by the following subcategories: patients with newly diagnosed epilepsy or with antiepileptic drug-resistant epilepsy, the type of epilepsy, patient age, and treatment period. RESULTS: Of a total of 77 patients, 49 patients (64%) attained 50% or more reduction of seizure frequency and of those patients 38 (49%) attained 75% or more reduction, with 18 patients (24%) becoming seizure-free from 6 to 180 (median 80.6 +/- 43.6) months of follow-up. Thirty-eight patients (49%) continued zonisamide monotherapy as of December 2003. Proportions of patients having 75% or more reduction in seizure frequency in subcategories were as follows; 56% in patients with newly diagnosed epilepsy and 48% in patients whose treatment was switched to zonisamide monotherapy owing to lack of efficacy of or adverse reaction to previous antiepileptic drugs; 60% in patients with localization-related epilepsies and 38% in patients with generalized epilepsies; and 49% in pediatric patients and 50% in adult patients. CONCLUSION: Long-term zonisamide monotherapy was efficacious in a wide range of patients with epilepsy. Zonisamide did not seem to exhibit a reduction in efficacy during long-term use of up to 180 months.

Adolescent↗