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Results for “Epilepsy, Generalized”

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PubMed2006

No association of single nucleotide polymorphisms in the micro-opioid receptor subunit gene with idiopathic generalized epilepsy.

We have investigated the reported association (p = 0.019) between the A118G single nucleotide polymorphism (SNP) of the opioid receptor micro subunit gene (OPRM1) and idiopathic absence epilepsy (IAE). Five SNPs, including A118G, were investigated by association studies in a sample of 240 probands with idiopathic generalized epilepsy (IGE), including 110 with IAE, and 257 controls. No significant association was found for A118G with IGE or IAE. The difference between the two studies was in the control samples that had significantly different allele frequencies (p = 0.00005), suggesting that population stratification may explain the earlier significant association with IAE. In the current study, none of the other four SNPs was significantly associated with IGE or IAE. Our results provide no support for association of A118G with either IAE or IGE and also exclude association in our sample of a small-to-moderate gene effect with IGE from a large part of OPRM1.

Chromatography, High Pressure Liquid↗

PubMed2002

No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 18q21.1.

A recent genome-wide scan showed strong evidence for a major locus for common syndromes of idiopathic generalized epilepsy (IGE) at the marker D18S474 on chromosome 18q21.1 (LOD score 4.5/5.2 multipoint/two-point). The present replication study tested the presence of an IGE locus in the chromosomal region 18q21.1. Our linkage study included 130 multiplex families of probands with common IGE syndromes. Eleven microsatellite polymorphisms encompassing a candidate region of 30 cM on either side of the marker D18S474 were genotyped. The two-point homogeneity LOD score for D18S474 showed strong evidence against linkage at the original linkage peak (Z = -18.86 at theta(m = f) = 0.05), assuming a recessive mode of inheritance with 50% penetrance. Multipoint parametric heterogeneity LOD scores < -2 were obtained along the candidate region when proportions of linked families greater than 35% were assumed under recessive inheritance. Furthermore, non-parametric multipoint linkage analyses showed no hint of linkage throughout the candidate region (P > 0.19). Accordingly, we failed to support evidence for a major IGE locus in the chromosomal region 18p11-18q23. If there is a susceptibility locus for IGE in this region then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.

Adolescent↗

PubMedDate not supplied

[Morphological and functional modifications of the acoustic system in golden hamsters with acoustic generalized epilepsy].

We studied the role of the neuronal circuit consisting of the superior olive-cochlear hair cells-auditory nerve complex in the pathophysiology of reflex audiogenic generalized epilepsy in the epileptic golden hamster. A direct role of the auditory function can be assumed from the genetic lesions found in these animals' acoustic system. These animals are a model of the anatomopathologic substrate of a type of hereditary neurosensorial hypoacusia.

Animals↗

PubMed2005

Cognitive function in idiopathic generalized epilepsy of childhood.

This study evaluated the cognitive profiles of children with idiopathic generalized epilepsy (IGE), uniformly treated with valproic acid with well-controlled seizures. Twenty-four were neuropsychologically evaluated. They comprised: 14 females, 10 males: 12 with generalized tonic-clonic seizures (GTCS), mean age 14y 4mo, SD ly 7mo, range 12y to 16y 4 mo; 12 with absence seizures (AS]) mean age 14y 5mo, SD ly 10mo, range 11y to 16y 4mo, with intellectual abilities within the normal range and age-appropriate scholastic skills, and 20 healthy controls (12 females, 8 males; mean age 14y 5mo, SD 1y 10mo, range 10y 7mo to 16y 7mo). As a group, children with IGE performed significantly poorer in all tests (non-verbal and verbal attention, verbal learning and memory, word fluency, and controlled sequential fine motor responses) excluding non-verbal memory. Analysis according to type of seizure revealed that both patient groups (AS and GTCS) had an attention deficit, whereas only children with AS showed deficits in verbal learning and memory, word fluency, and controlled fine motor responses. These results suggest a long-term risk of learning impairment for children with IGE, even if they have normal intelligence and their seizures are well controlled.

Adolescent↗

PubMed2007

Allelic association of a truncation mutation of the KCNMB3 gene with idiopathic generalized epilepsy.

The gene encoding the beta3-subunit regulatory subunit (KCNMB3) of large conductance calcium-sensitive potassium (BK) channels represents a positional and functional candidate gene for idiopathic generalized epilepsy (IGE). A single base pair deletion in exon 4 of KCNMB3 (delA750) alters/truncates the terminal 21 amino acids of the 3-subunit and affects channel inactivation of the beta3b-isoform. The present association study tested whether the KCNMB3 delA750 mutation confers susceptibility to common IGE syndromes. In total, 592 unrelated German IGE patients and 462 healthy population controls were genotyped for the delA750 truncation mutation. The frequency of the delA750 mutation was significantly increased in the IGE patients (7.9%) compared to that in the controls (5.5%; P = 0.016, one-sided; OR = 1.52; 95%-CI: 1.05-2.21). The increase of the delA750 frequency was accentuated in 312 patients exhibiting typical absence seizures (8.8%, P = 0.005, one-sided; OR = 1.72; 95%-CI: 1.13-2.62) relatively to that observed in the 237 patients with myoclonic seizures on awakening (7.2%; P = 0.11, one-sided; OR = 1.36; 95%-CI: 0.85-2.19), when compared with controls. The present results suggest that the functional KCNMB3 beta3b-truncation confers a common epileptogenic effect preferentially to the ictogenesis of typical absence seizures.

Alleles↗

PubMed2005

Association analysis of malic enzyme 2 gene polymorphisms with idiopathic generalized epilepsy.

PURPOSE: Linkage disequilibrium mapping revealed allelic and haplotypic associations between single-nucleotide polymorphisms (SNPs) of the gene encoding the malic enzyme 2 (ME2) and adolescent-onset idiopathic generalized epilepsy (IGE). Homozygote carriers of the associated ME2 haplotype had a sixfold higher risk of IGE compared with any other genotype. The present population-based association study tested whether genetic variation of the ME2 gene confers susceptibility to common IGE syndromes in the German population. METHODS: The study included 666 German healthy control subjects and 660 German IGE patients (IGE group), of which 416 patients had an age at onset in adolescence (IGEado group). Genotyping was performed for six SNPs and one dinucleotide repeat polymorphism, all located in the ME2 region. RESULTS: Neither allele nor genotype frequencies of any ME2 polymorphism differed significantly between the controls and the IGE groups (p > 0.22). No hint of an association of the putative risk-conferring haplotype was seen, when present homozygously, in both IGE groups compared with controls (p > 0.18). CONCLUSIONS: These results do not support previous evidence that genetic variation of the ME2 gene predisposes to common IGE syndromes. Thus if a recessively inherited ME2 mutation is present, then the size of the epileptogenic effect might be too small or not frequent enough to detect it in the present IGE sample.

Age of Onset↗

PubMed1991

Regional brain perfusion changes in patients with primary generalized epilepsy assessed by Tc99m HM-PAO and SPECT.

Cerebral distribution of Tc99m-hexamethylprolenaminoxim (HMPAO) was investigated using single photon emission computerized tomography (SPECT) in 34 patients with primary generalized epilepsy (PGE) during the interictal state. These findings were compared with those in a control group of 9 healthy volunteers. In control subjects uniform selective uptake of HMPAO in cortex, basal ganglia and thalamus was found. In 30 patients (88%) decreased regional perfusion was found as follows: in the cortical region in 6 patients (18%), in the region of the basal ganglia or thalamus in 7 (20%), and in both regions in 17 patients (50%). Four patients had normal SPECT findings. The obtained results permit a hypothesis that the PGE should not be strictly differentiated from the focal epilepsy. A possible explanation of the pathophysiology of PGE has also been discussed.

Adolescent↗

PubMed1978

Generalized epilepsy with bilateral synchronous spike and wave discharge. New findings concerning its physiological mechanisms.

A hypothesis for the mechanism of generalized spike and wave discharge in human generalized epilepsy is proposed in the light of findings obtained in feline generalized penicillin epilepsy. It is postulated that generalized bilaterally synchronous spike and wave discharge depends upon a diffuse and relatively mild state of cortical hyperexcitability which increases the responsiveness of cortical neurons. Afferent thalamo-cortical volleys normally involved in the genesis of spindles and recruiting responses are most likely to precipitate spike and wave discharges under these conditions. The spike and wave pattern probably results from the activation of a recurrent intracortical inhibitory pathway which becomes activated when cortical neurons discharge in greater number and more repetitively than is normally the case. During spike and wave discharges a large number of neurons oscillate between short periods of excitation, corresponding to the spike, and longer periods of inhibition, corresponding to the slow wave component of the spike and wave complex. This disrupts the normal transactional processes of cortical neurons which are presumably responsible for mental activity, particularly for the close integration of perception, cognition and voluntary motor responsiveness. The degree of this interference varies greatly and in mild absence seizure it is not justified to speak of "loss of consciousness". The fundamental disturbance in absence seizures brought about by the generalized cortical spike and wave discharges is therefore better regarded as a "clouding of the mind". Loss of consciousness can be said to occur only when the interference with mental activity becomes particularly intense. Loss of consciousness in absence seizures can therefore not be used as an argument in favor of primary involvement of higher brain-stem mechanisms.

Animals↗

PubMed2006

Diagnostic issues and treatment of cryptogenic or symptomatic generalized epilepsies.

To clarify the diagnostic issues and treatment of patients with cryptogenic or symptomatic generalized epilepsies, not including West syndrome (WS), we investigated electroclinical change during the clinical course, and treatment effects in these patients. The selection criteria were minor generalized seizures as their main seizure type and diffuse epileptic discharges as their main EEG findings. Regarding EEG, we included EEGs that predominantly displayed multifocal spike-waves because of the inclusion of severe epilepsy with multiple independent spike foci (SE-MISF). We divided the subjects into two groups according to their main seizure types: Group A (54 patients) with brief tonic seizures and Group B (24 patients) with myoclonic seizures and/or atypical absences. The main epileptic syndromes were considered to be Lennox-Gastaut syndrome and SE-MISF in Group A, and epilepsy with myoclonic-astatic seizures in Group B. A history of WS was often seen in Group A, but it was exceptional in Group B. During the clinical course, seizure types did not basically change in Group A. EEG patterns were changeable in both groups. Although there was some overlap in electroclinical manifestations among epileptic syndromes, a transition between the two groups was not seen. High-dose valproate and ethosuximide were the most effective in Groups A and B, respectively. Long-term prognosis was significantly more favorable in Group B than in Group A.

Adolescent↗

PubMed2002

No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 5 in families with typical absence seizures.

A recent genome-wide scan revealed suggestive evidence for two susceptibility loci for idiopathic generalized epilepsy (IGE) in the chromosomal regions 5p15 and 5q14-q22 in families with typical absence seizures. The present replication study tested the validity of the tentative IGE loci on chromosome 5. Our study included 99 multiplex families in which at least one family member had typical absence seizures. Parametric and non-parametric multipoint linkage analyses were carried out between the IGE trait and 23 microsatellite polymorphisms covering the entire region of chromosome 5. Multipoint parametric heterogeneity lod scores < -2 were obtained along chromosome 5 when a proportion of linked families greater than 50% was assumed under recessive inheritance and > 60% under dominant inheritance. Furthermore, non-parametric multipoint linkage analyses revealed no hint of linkage throughout the candidate region (P > 0.05). Accordingly, we failed to support previous evidence for common IGE loci on chromosome 5. If there is a susceptibility locus for IGE on chromosome 5 then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.

Chromosome Mapping↗

PubMed2001

Prolonged cortical silent period after transcranial magnetic stimulation in generalized epilepsy.

Transcranial magnetic stimulation (TMS) produces a cortical silent period (CSP) during a voluntary contraction. The duration of the CSP was used to assess the level of intracortical inhibition in patients with untreated idiopathic generalized epilepsy (IGE). Mean CSP duration was assessed at three TMS stimuli in 21 patients with IGE compared with 19 normal control subjects. Mean CSP duration was increased at all stimulus intensities, indicating that intracortical inhibition is increased in patients with IGE.

Adolescent↗

PubMed2001

Adult-onset idiopathic generalized epilepsy: clinical and behavioral features.

PURPOSE: To identify and define clinical and behavioral features of patients with adult-onset idiopathic generalized epilepsy (IGE). METHODS: We reviewed the charts of 313 IGE patients at the NYU Comprehensive Epilepsy Center over the past 5 years to identify patients with adult onset (18 years old or older). We excluded patients with childhood or adolescent symptoms that suggested absence, myoclonic, or tonic-clonic seizures, as well as those with a history of significant head injury or other known causes of localization-related epilepsy. RESULTS: Forty-two (13.4%) patients had a clear onset of IGE in adulthood; average age of onset was early 20s (mean, 23.8 years; range, 18-55 years). Twenty-one patients had adult myoclonic epilepsy (AME, 50%), and three had generalized tonic-clonic seizures on awakening (GTCS-A, 7%). More than two thirds (n=30) are well controlled with current antiepileptic drugs (AEDs), and almost 90% are currently employed (n=37). One third were diagnosed and treated for mental disorders, including depression (n=12), anxiety (n=7), obsessive-compulsive personality disorder (n=2), and postictal psychosis (n=1). CONCLUSIONS: Adult-onset IGE is associated with a good prognosis. An association may exist between psychological disorders, psychotropic medication, and level of seizure control in adults with IGE.

Adolescent↗

PubMed2005

Genetic dissection of photosensitivity and its relation to idiopathic generalized epilepsy.

Photosensitivity or photoparoxysmal response (PPR) is a common and highly heritable electroencephalographic trait characterized by an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. PPR occurs frequently associated with idiopathic generalized epilepsies (IGEs). The present genomewide linkage scan was designed to map susceptibility loci for PPR and to explore their genetic relationship with IGE. The study included 60 families with at least two siblings displaying PPR. To dissect PPR-specific and IGE-related susceptibility loci, we defined two distinct family subgroups, comprising 19 families with predominantly pure PPR and photosensitive seizures (PPR-families) and 25 families, in which PPR was strongly associated with IGE (PPR/IGE-families). MOD score analyses provided significant evidence for linkage to the region 6p21.2 in the PPR-families (empirical p = 0.00004) and suggestive evidence for linkage to the region 13q31.3 in the PPR/IGE families (p = 0.00015), both with a best-fitting recessive mode of inheritance. In the PPR/IGE-families, linkage evidence was even stronger (p = 0.00003) when the trait definition was broadened by IGE traits. Our study shows two PPR-related susceptibility loci, depending on the familial background of IGE. The locus on 6p21.2 seems to predispose to PPR itself, whereas the locus on 13q31.3 also confers susceptibility to IGE.

Chromosomes, Human, Pair 13↗

PubMed2000

Interhemispheric threshold differences in idiopathic generalized epilepsies with versive or circling seizures determined with focal magnetic transcranial stimulation.

The interhemispheric difference of the motor-cortical threshold (IDMT) was studied with focal magnetic transcranial stimulation (TCS) in ten patients with idiopathic generalized epilepsy (IGE) who also displayed versive or circling seizures (IGEvc). The data were compared with those obtained from two control groups; 13 patients with IGE without asymmetrical motor seizures, and 25 normal volunteer subjects. The IDMT, referred to as the percentage of maximum stimulator output, was assessed by focal TCS applied to the hand areas. Seven patients with IGEvc and only one patient with IGE had an interhemispheric motor threshold beyond the normal range. The IDMT in IGEvc patients was significantly higher compared to that of IGE patients and normal individuals. An interhemispheric imbalance of cortical excitability may explain lateralized ictal motor manifestations in patients with IGEvc.

Adolescent↗

PubMed1991

Sleep, arousal and electroclinical manifestations of generalized epilepsy with spike wave pattern.

Polygraphic sleep investigations have shown that, in patients with generalized epilepsy and spike wave patterns, ictal electroclinical manifestations occur in intermediate periods between waking state-NREM sleep and NREM sleep-REM sleep. These physiological microfluctuations represent an important dynamic principle. These minor fluctuations are detectable with a special method of microanalysis of sleep. Such a microanalysis shows that the attacks of patients with generalized spike wave patterns are linked with arousal reactions. This may result in prolonged intermediate states causing augmentation of the paroxysms and thus representing a vicious circle.

Arousal↗

PubMed1999

Length variation of a polyglutamine array in the gene encoding a small-conductance, calcium-activated potassium channel (hKCa3) and susceptibility to idiopathic generalized epilepsy.

The present association study tested whether length variations of two adjacent polymorphic CAG repeats in the coding sequence of a small-conductance, calcium-activated potassium channel (hKCa3) confer susceptibility to common subtypes of idiopathic generalized epilepsy (IGE). We found no significant difference in the allelic length distribution of the CAG repeats between 290 healthy German controls and the entire sample of 126 German IGE patients (Wilcoxon rank-sum test, P = 0.44) or two subgroups, comprising either 78 patients with juvenile myoclonic epilepsy (Wilcoxon rank-sum test, P = 0.74) or 59 patients with idiopathic absence epilepsies (Wilcoxon rank-sum test, P = 0.44). Moreover, the allelic distribution in parents-child trios of 46 IGE offspring did not differ significantly between the transmitted and non-transmitted parental alleles (Wilcoxon rank-sum test, P = 0.48). Therefore, our association study provides no evidence that length variations of polyglutamine arrays in the N-terminus of the hKCa3 channel exert a frequent and relevant effect in the epileptogenesis of common subtypes of IGE.

Adult↗

PubMed1997

Event-related potentials suggest slowing of brain processes in generalized epilepsy and alterations of visual processing in patients with partial seizures.

Event-related potentials were recorded in two auditory tasks and in one visual task from 13 patients with partial seizures (PS), 12 patients with idiopathic generalized epilepsy (IGE), and healthy age-matched participants. IGE patients had delayed latencies in the auditory tasks, with the delay being reliable already at N1, and continuously increasing at N2b and at P3. The P3 delay correlated with duration of epilepsy both in IGE and in PS patients. In the visual task, the posterior N2 was delayed in PS patients, in particular in PS patients with temporal focus. Resembling the delays as found in healthy elderly adults, the delays with auditory stimuli might reflect a slowing of brain processes as it occurs in healthy aging. The isolated delay of posterior N2 in temporal PS patients might indicate a specific impairment of the occipito-temporal visual pathway. Taken together, event-related potentials prove to be a very sensitive instrument for measuring altered brain functioning in epileptic patients, when compared to measurement of overtly visible responses.

Adult↗

PubMed2003

Exploring new gene discoveries in idiopathic generalized epilepsy.

Most epilepsies are categorized under the umbrella term "idiopathic;" these seizure disorders lack a known cause. New genetic technologies are rapidly identifying specific genes responsible for idiopathic generalized epilepsies (IGEs) and are gradually taking the "I" out of "IGE." Ion channel (both voltage- and receptor-mediated) mutations have been linked to a variety of epilepsies considered idiopathic. Gene errors alter excitability in various ways, depending on the mutation, the regional network, and the stage of brain development. The majority of mutations prolong depolarization, favor repetitive firing, and alter neurotransmitter release or postsynaptic sensitivity at central synapses, but the reason for specific seizure types is unclear. Further analyses of these gene mutations and their effects on the developing brain are providing critical clues in the search to explain the origin of "idiopathic" epilepsy.

Animals↗