SEARCH · PubMed Health

Results for “Epilepsy, Generalized”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

PubMed2004

Congenital ocular motor apraxia associated with idiopathic generalized epilepsy in monozygotic twins.

Identical female twins (age 11 years) with congenital ocular motor apraxia and generalized idiopathic epilepsy are reported. Their presenting symptoms were a long history of abnormal head and eye movements. One twin developed partial sensory seizures. The patients underwent 16-channel EEG, electro-oculographic recordings, MRI of the brain, and genetic and metabolic investigations. EEG findings were consistent with idiopathic generalized epilepsy. Electrooculographic recordings of the saccades confirmed an inability to elicit horizontal saccades without preceding head movement; saccades to the left were better than saccades to the right. MR scans for one twin showed normal findings, however, for the twin who had meningitis they revealed asymmetry between the right and left temporal lobes but no specific abnormality. DNA analysis using a series of autosomal polymorphic markers confirmed the monozygocity of the twins. White blood cell enzyme analysis excluded Sandhoff disease, Tay-Sachs disease, GM1 gangliosidosis, metacromatic leucodystrophy, Gaucher disease, Niemann-Pick disease (A and B), and Krabbe leucodystrophy. Albumin and immunoglobulin (IgA, IgG, and IgM) levels were normal. It is concluded that autosomal recessive inheritance seems the most likely explanation here, as recent studies have found insertion and missense mutations of the aprataxin gene which have been related to an early onset form of ataxia with ocular motor apraxia and hypoalbuminaemia.

Apraxias↗

PubMed2003

[Treatment termination in children with idiopathic generalized epilepsy and cryptogenic focal epilepsy].

The regression of epileptic attacks after a period for remission brings hope, particularly for a sick child's parents, for prompt treatment termination. This process, however, is related to the risk that the disease will recur. The paper is about the evolution of these changes in EEG and the assessment of disease recurrence in the course of treatment and upon therapy termination in patients taking valproic acid preparations (VPA) during idiopathic generalized epilepsy (IGE) and those taking carbamazepine (CBZ) preparations during cryptogenic focal epilepsy (CFE). A total of 121 patients in whom the attacks regressed as a result of monotherapy, were subjected to the assessment. The patients were classified into 2 groups: the first group of 52 patients treated with VPA (IGE), patients' age at the beginning of treatment--from 6 to 14, and the second group of 69 patients treated with CBZ (CFE), patients' age at the beginning of treatment--from 5 to 12. In patients suffering from IGE, an absence of attacks prevailed; while in those with CFE--the secondary generalized ones prevailed. The drug dosage reduction lasted from 3 to 24 months. The observation time at treatment termination was 2 years. 10 routine EEG tests were assessed in each patient. Attack regression was achieved mainly within 2 weeks, sporadically up to 6 months. In the initial EEG tests 4 (5.8%) of the patients with partial seizures had normal records, in the remaining 94.2%--the records were abnormal. Throughout the duration of the treatment, systematic improvement of EEG was noted in groups 1 and 2. At the commencement of the dosage reduction, the EEG irregularities were maintained in 9% of the patients with IGE and in 26% of those with CFE, increasing during reduction until the discontinuance of the medication. Frequency of attack recurrences was twice as large in the patients with IGE (mainly after the end of treatment) than in those with CFE, where they occurred during the reduction period and up to 3 months after the end of treatment. The recurrence of the disease in children of the first group was only preceded in one third by irregularities in EEG; on the contrary, it occurred in two thirds of the second group. The morphology of changes was non-homogeneous.

Adolescent↗

PubMed2004

fMRI activation during spike and wave discharges in idiopathic generalized epilepsy.

The objectives of this study were to evaluate the haemodynamic response of the cerebral cortex and thalamus during generalized spike and wave or polyspike and wave (GSW) bursts in patients with idiopathic generalized epilepsy (IGE). The haemodynamic response is measured by fMRI [blood oxygenation level-dependent (BOLD) effect]. We used combined EEG-functional MRI, a method that allows the unambiguous measurement of the BOLD effect during bursts, compared with measurements during the inter-burst interval. Fifteen patients with IGE had GSW bursts during scanning and technically acceptable studies. fMRI cortical changes as a result of GSW activity were present in 14 patients (93%). Changes in the form of activation (increased BOLD) or deactivation (decreased BOLD) occurred symmetrically in the cortex of both hemispheres, involved anterior as much as posterior head regions, but were variable across patients. Bilateral thalamic changes were also found in 12 patients (80%). Activation predominated over deactivation in the thalamus, whereas the opposite was seen in the cerebral cortex. These results bring a new light to the pathophysiolocal mechanisms generating GSW. The spatial distribution of BOLD responses to GSW was unexpected: it involved as many posterior as anterior head regions, contrary to the usual fronto-central predominance seen in EEG. The presence of a thalamic BOLD response in most patients provided, for the first time in a group of human patients, confirmation of the evidence of thalamic involvement seen in animal models. The possible mechanisms underlying these phenomena are discussed.

Adolescent↗

PubMed1985

Prognostic factors of primary generalized epilepsy: a reappraisal of 96 cases in terminal remission.

Ninety-six patients whose diagnosis was definitively confirmed as primary generalized epilepsy (PGE) were divided into two groups according to the duration of recurrent seizures--A group for less than 7 years and B group for more than 7 years. The patients of both groups were completely free of seizures for more than 3 years at the time of the survey. A retrospective comparison was made between these two groups in terms of clinical and EEG features. Emphasis was placed on the B group which was characterized by an unfavorable seizure outcome. From a prognostic point of view, the risk factors indicative of an unfavorable outcome of seizures were found as follows: a) the presence of generalized tonic-clonic convulsions (GTCs) prior to the occurrence of minor seizures and persisting GTCs following the subsidence of minor seizures, b) scanty epileptic EEG findings in spite of the sporadic occurrence of GTCs, and c) GTCs tended to associate with various seizure-inducing factors. As a conclusion, along with appropriate drug treatment, the necessity of comprehensive approaches to the patients' everyday life was emphasized in order to achieve a favorable seizure outcome.

Adolescent↗

PubMed1987

Monotherapy with valproate in primary generalized epilepsies.

Sodium valproate enteric-coated tablets were administered as monotherapy to 118 patients (median age, 19 years) with primary generalized epilepsies. More than half (56%) of these patients were transferred from prior drug therapy, most of them because of inadequate seizure control, and some because of adverse effects. Seventy-one percent of the patients experienced tonic-clonic seizures, either alone or in combination with other types of seizures, principally absences. Mean duration of follow-up was 18 months (median, 17 months; range, 1-68 months). At a mean daily dosage of less than 20 mg/kg, 83% of the patients became seizure-free. Therapy was equally effective against tonic-clonic seizures, absences, and myoclonic seizures. Tonic-clonic seizures were suppressed in 85% of cases (89% when patient had only one seizure type), absences in 82% (95% when patient had only one seizure type), and myoclonic seizures in 82%. Paroxysmal activity was present in 88% of the electroencephalogram (EEG) records before valproate monotherapy, and in 32.4% at the study's end. These results were achieved with generally mild and mostly transient side effects; side effects were reported by 16% of patients during the first month, and 2% at the last follow-up. No hematologic or hepatic toxicity was observed. The lag time between attaining steady-state serum concentrations and achieving maximal clinical improvement suggests that sodium valproate monotherapy should be given an adequate trial to ensure that patients derive the greatest possible benefit before adding or switching to another drug.

Adolescent↗

PubMed2003

Effects of remacemide in two models of genetically determined generalized epilepsy, the GAERS and the audiogenic Wistar AS.

The antiepileptic effects of remacemide were assessed in two models of genetically determined generalized epilepsy. The model of non-convulsive epilepsy used was a model of absence seizures, the GAERS (genetic absence epilepsy rats from Strasbourg), and the model of convulsive seizures was an audiogenic rat model, the Wistar AS. In the eight GAERS studied, the three doses of remacemide (20, 40, and 80 mg/kg) dose-dependently reduced the expression of spike-and-wave discharges (SWDs) that had almost totally disappeared at the highest dose used, 80 mg/kg. However, at the latter dose, the effect of remacemide may be partly due to a change in the vigilance level of the animals. In the Wistar AS, the dose of 20 mg/kg prolonged by twofold the latencies to wild running and tonic seizures, and prevented their expression in one rat out of the eight studied. At 40 mg/kg, the expression of wild running and tonic seizures was inhibited in seven and maintained in one of the eight rats studied. The present results support the effects of remacemide in tonic/clonic seizure, which was the first target of the drug, and confirm the effect of the anticonvulsant on absence seizures.

Acetamides↗

PubMed1989

Corpus callosum stimulation and stereotactic callosotomy in the management of refractory generalized epilepsy. Preliminary communication.

Corpus callosum stimulation produced by chronically implanted electrodes, placed either by craniotomy or stereotactically, failed to control refractory generalized epilepsy in humans and also in experimentally produced penicillin epilepsy in cats. However, the patients that suffered craniotomy, frontal lobe retraction or pneumoencephalograms, without callosal section, showed remarkable improvement of their seizure condition due to these unspecific manipulation effects. Stereotactic anterior callosotomy emerged as a sequel of these functional neurosurgical findings, and as an alternative procedure to preclude undesirable neuropsychological and neurological side effects of split brain syndrome and of brain retraction, associated to conventional callosotomy. Ten patients with various disabling convulsive disorders have undergone this new operation, which showed to be less traumatic and better tolerated than open callosotomy.

Adolescent↗

PubMedDate not supplied

Idiopathic generalized epilepsy: magnetic stimulation of motor cortex time-locked and unlocked to 3-Hz spike-and-wave discharges.

In 20 patients with idiopathic generalized epilepsy who showed typical 3-Hz spike-and-wave (SW) EEG complexes, we studied the corticospinal motor output with a transcranial electromagnetic stimulator. First we measured the corticospinal discharge threshold for both hemispheres in the patient group and compared it with that of 10 age- and sex-matched volunteers. Threshold was significantly higher in the patient group, regardless of whether subjects were treated with antiepileptic drugs (AEDs). In 4 patients with very frequent SW paroxysms, we were able to study motor evoked potential (MEP) changes time-locked to epileptic EEG transients. The EEG signal was recorded bipolarly (C3-P3, C4-P4) by scalp needle-electrodes. For a given stimulus intensity, we collected and measured MEPs occurring during the spike or the wave portion of the SW complexes. Data were compared with those of MEPs obtained time-locked to normal EEG segments. MEP size was significantly decreased when the cortical stimulus was time-locked to the wave component, and was decreased or unchanged when the stimulus was time-locked to the spike. Magnetic stimulation never produced remarkable side effects.

Adult↗

PubMed1981

Generalized epilepsy with spike-wave paroxysms as an epileptic disorder of the function of sleep promotion.

A new hypothesis is offered regarding the pathomechanism of generalized epilepsy with spike-wave paroxysms (GESw) based on the pertaining literature and personal investigations. The first section is devoted to a critical overview of the development of theories regarding GESw. The centrencephalic theory, the debate on subcortical versus cortical origin, the "corticoreticular" hypothesis of Gloor and, finally, the "dyshormic" concept of Niedermeyer are outlined. In the next section it is shown that there is a particular optimum zone between sleep and wakefulness and between REM and slow wave sleep which highly favours the occurrence of spike-wave paroxysms. According to our investigations into the dynamics within this critical zone, the spike-wave paroxysms always appear with characteristic fluctuations of the level of consciousness where the changes towards awakening are always followed by rebounds towards sleep. Hence, the dynamic properties of this unstable border zone become especially interesting in the genesis of spike-wave paroxysms. It has been shown that even without epilepsy, a dynamics can be observed in the micro-oscillations in the depth of sleep which could be interpreted according to the reciprocal induction regulation model. In our concept the process of falling asleep emerges from rebounds of the sleep promoting system in response to sensory inputs streaming in from the external environment. According to this model, arousal influences in sleep have a sleep promoting effect. We interpret in this way all synchronized EEG reactions elicited by sensory stimuli and we consider K-complex type synchronization reactions as a "building stone" of the process of falling asleep which contains the whole process in concentrated form. The manifold similarities between the K-complex and the spike-wave pattern are demonstrated. On this basis spike-wave paroxysms can be regarded as an epileptic "caricature" of the sleep induction momentum reflected in the K-complex phenomenon. Hence, the GESw is the epileptic disorder of the sleep promotion function. This hypothesis resolves and explains many contradictory features of our knowledge about this mechanism and gives a new biologically oriented framework for further research. In the light of the hypothesis it has been attempted to interpret some of the characteristic features of the GESw: the genetic determination, the age dependency, the link with the sleep-waking cycle as well as the functional-anatomical characteristics and the symptoms of the seizures.

Adolescent↗

PubMed1996

Common subtypes of idiopathic generalized epilepsies: lack of linkage to D20S19 close to candidate loci (EBN1, EEGV1) on chromosome 20.

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conducted in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an "exclusion region" (lod scores below-2) varied from 0.5 cM up to 22 cM on either side of D20S19 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence.

Chromosome Mapping↗

PubMed1990

Pattern-reversal visual evoked potentials recorded in children with generalized epilepsy.

Visual potentials evoked by pattern reversal (PRVEPs) were studied in 64 normal subjects (age range 7 to 15 years) and in 15 patients with primary generalized epilepsy (age range 8 to 13 years), 10 of whom were without anticonvulsant medication. Most of them were studied during sodium valproate (VPR) therapy and some during carbamazepine (CBZ) medication. A Quadristim set (Alvar) was used to present checkerboard patterns on a TV monitor, to amplify the EEG signals and to average and plot the evoked potentials. The potentials were elicited by binocular full-field 2/s checkerboard reversals, recorded from an electrode 4 cm above the inion, and analyzed for latency, amplitude and waveform. Our PRVEP measurements examined peak latency of positive P2 (or P100) component and trough-to-peak amplitude on N1P2 wave complex. The degree of similarity between pairs of PRVEP plots were determined by Pearson correlation coefficient r for an analysis time of 150 ms. In most of our patients, no pronounced influence of the disease itself on the parameters and waveform of the normal PRVEP pattern was demonstrated if anticonvulsant drugs were not taken. In patients who were under complete seizure control, the anticonvulsant did not change the PRVEP morphology as well. The PRVEP abnormality was most pronounced in patients who were taking anticonvulsant medication, but whose seizures were poorly controlled. This pattern distortion can be revealed by the correlation coefficient, but not by other PRVEP parameters. Therefore, this coefficient may be useful as a sensitive and objective measure both of PRVEP distortion and PRVEP improvement. Our results give further evidence that nondemyelinating disorders, but with synaptic transmission defects, can produce measurable changes in PRVEP morphology.

Adolescent↗

PubMedDate not supplied

Reproductive endocrine disorders in women with primary generalized epilepsy.

It is known that women suffering from temporal lobe epilepsy may frequently present reproductive endocrine disorders (REDs). We hypothesized that a high occurrence of REDs could be found also in primary generalized epilepsy (PGE), and therefore investigated the hormonal and ovarian echographic profiles in 20 PGE female patients of reproductive age. Fourteen reported normal menstrual cycles, while 6 complained of longstanding menstrual irregularities. All but three patients were receiving antiepileptic drug (AED) therapy. In all subjects, the basal levels of gonadotropins, prolactin, and gonadal steroids were assayed. The response of luteinizing hormone (LH) to gonadotropin-releasing hormone was also investigated and ovarian ultrasonographic findings were evaluated. In five of six patients with menstrual problems (25% of the group), a well-defined RED was diagnosed (polycystic ovarian disease in three cases and hypothalamic ovarian failure in two). The 14 patients with normal menstrual cycles showed an elevation of mean basal follicle-stimulating hormone and prolactin, and a blunting of mean LH response. Our results suggest that a high occurrence of REDs may be found also in PGE. We hypothesize that a neurotransmitter dysfunction might be the common pathogenetic mechanism resulting in both REDs and PGE. The hormonal alterations observed in the patients with normal menstrual cycles seem to support our hypothesis. Previous data seem to rule out a possible AED effect accounting for the hormonal findings observed in our series. However, further studies are needed to confirm our preliminary results.

Adolescent↗

PubMedDate not supplied

Critical review of the animal models of generalized epilepsies.

The state of the art for models of generalized seizures in animals is satisfactory, but improvable for what concerns primary generalized seizures of Petit-Mal type. Other models of secondary generalized seizures are available allowing acceptable ways of studying some mechanisms of epileptogenesis, and/or screening potentials new AEDs. For other forms of seizures, such as amyotonic fits, there are no models. By and large, models of epilepsy are lagging behind models of seizures as most of the former when reproduced in the laboratory are short lived. Spontaneously occurring epilepsies in cats should be studied more widely as they may provide a wide variety of epileptic conditions not dissimilar from the ones seen in humans. Overall, models of seizures and epilepsies are more advanced than the models of most neuropsychiatric conditions.

Animals↗

PubMedDate not supplied

Considerations on the significance attributed to unusual cerebral histological findings recently described in eight patients with primary generalized epilepsy.

The authors, although they express appreciation of the importance of publishing careful anatomical reports in cases of epilepsy, express some doubts concerning the pathological nature of the histological features reported by Meencke and Janz in the brains of eight patients suffering from primary generalized epilepsy. As illustrated and described, most of the histological findings considered abnormal are commonly seen in neurologically normal controls. Also, true "minor dysgenetic changes" have been observed in individuals free of cerebral disorders. Furthermore, the hypothesis drawn from the neuropathological observations to explain the etiopathogenesis of this category of epilepsy and the physiopathogenesis of the seizures does not seem acceptable to the authors.

Brain↗

PubMed1987

Diagnosis of primary generalized epilepsy in a cow.

On the basis of history, electrodiagnostic and neuropharmacologic studies, and results of laboratory testing and necropsy, a seizure disorder of 1.5 years' duration in an 8-year-old Hereford cow was diagnosed as primary generalized epilepsy. Evidence of metabolic, toxicologic, head trauma, or genetic cause of the seizures was not found. A morphologic cause for the convulsions also was not detected. One naturally occurring seizure was recorded electroencephalographically, but interictal EEG abnormalities were not seen. Attempts to evoke a seizure with photostimulation or therapeutic doses of acepromazine, ketamine, tripelennamine, and estradiol cypionate were unsuccessful. The seizure threshold for the CNS stimulant pentylenetetrazol was found to be less than 6 mg/kg, IV; the seizure threshold in a control cow was found to be greater than 12 mg/kg, IV. The pharmacologic protocol used for this cow may be useful for diagnosis of epilepsy in other animals.

Animals↗

PubMed1997

Linkage analysis between idiopathic generalized epilepsies and the GABA(A) receptor alpha5, beta3 and gamma3 subunit gene cluster on chromosome 15.

INTRODUCTION: We tested the hypothesis that genetic variants within the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster on chromosome 15q11-q13 confer genetic susceptibility to common subtypes of idiopathic generalized epilepsy (IGE). MATERIAL AND METHODS: Ninety-four families were selected from IGE patients with either juvenile myoclonic epilepsy (JME), juvenile (JAE) or childhood absence epilepsy (CAE). Cosegregation was tested between dinucleotide polymorphisms associated with the human GABA(A) alpha5, beta3 and gamma3 subunit gene cluster and three different IGE trait models. RESULTS: Evidence against linkage to the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster was found in the entire family set and subsets selected from either CAE or JAE. In 61 families of JME patients, a maximum lod score (Zmax=1.40 at Theta(max)=0.00) was obtained for a broad IGE spectrum ("idiopathic" generalized seizure or generalized spike and wave discharges in the electroencephalogram) assuming genetic heterogeneity (alpha=0.37; P=0.06) and an autosomal recessive mode of inheritance. CONCLUSION: The possible hint of linkage in families of JME patients emphasizes the need for further studies to determine whether a recessively inherited gene variant within the GABA(A) alpha5, beta3 and gamma3 subunit gene cluster contributes to the pathogenesis of "idiopathic" generalized seizures and associated EEG abnormalities in a proportion of families.

Chromosomes, Human, Pair 15↗

PubMed1986

Neuronal sensitivity to GABA and glutamate in generalized epilepsy with spike and wave discharges.

In awake but painlessly immobilized cats the extracellular activity of the same cortical neurons was recorded before and for 2 to 5 h after the injection of penicillin G (350,000 IU/kg, i.m.) during the development of generalized epilepsy with bilaterally synchronous spike and wave discharges. Possible changes in their sensitivity to microiontophoretically applied glutamate and GABA during this period were searched for using computer-generated periejection histograms at intervals of about 30 min. In contrast to reported studies in other models of epilepsy, glutamate excited and GABA depressed virtually all neurons tested during fully developed spike and wave epilepsy. Spike height was not apparently affected either by the amino acids or by the development of epilepsy. Comparison of relative thresholds for the above effects on rhythmical neuronal activity associated with spike and wave discharge versus effects on random neuronal activity during the interburst periods, supported the idea that spikes and waves result from strong excitatory and inhibitory synaptic drives of the neurons. In all neurons until the appearance of spike and wave discharges, changes in the effect of amino acids, if observed, were small and statistically nonsignificant. This suggests that the hyperexcitability of cortical neurons which reportedly leads to the appearance of spike and wave discharges depends on mechanisms other than an increase in sensitivity to glutamate or a desensitization to GABA. Sometimes the sensitivity to GABA decreased later in this experimental model when the very frequent appearance of spike and wave discharges eventually led to EEG tonic-clonic seizures.

Animals↗

PubMed1986

Benzodiazepine/barbiturate/GABA receptor-chloride ionophore complex in a genetic model for generalized epilepsy.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) acts through postsynaptic receptor sites which regulate membrane chloride ion channels. The GABA receptor-ionophore complex also contains modulatory receptor sites for two classes of centrally acting drugs, one for the benzodiazepines, and a second for both barbiturates and related depressants and for picrotoxin and related convulsants. The presence of these drug modulatory sites, directly on the GABA receptor protein, is consistent with other experimental observations; blocking GABA function can cause seizures, and augmenting GABA function can afford protection against seizures. This, and other circumstantial evidence, has suggested the possibility that a functional GABA deficit may be involved in some kinds of human epilepsy. Some neurochemical markers for GABA synapses have been reported to be altered in certain animal models as well as in human temporal lobe epilepsy. We have examined the postsynaptic GABA receptor complex using receptor binding assays for GABA, benzodiazepine (BZ), and barbiturate receptor sites in the seizure-susceptible gerbil, a genetic model of generalized epilepsy. A 30% deficit in BZ receptor binding was observed in the midbrain of seizure-sensitive animals relative to normal controls. This was shown by quantitative brain-slice binding autoradiography to involve a decrease in the number of binding sites in the substantia nigra (SN) and periaqueductal gray regions. A deficit in membrane receptors for BZs (which are linked to a subtype of postsynaptic GABA receptors) in a crucial region of brain might therefore contribute to seizure susceptibility in some kinds of epilepsy.

Animals↗