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 253 records · Page 14Linked to original sources

PubMed2005

Properties of antiepileptic drugs in the treatment of idiopathic generalized epilepsies.

Although valproate is considered to be the drug of first choice for the treatment of idiopathic generalized epilepsies (IGEs), other antiepileptic drugs (AEDs), both old (ethosuximide, clobazam, and clonazepam) and new (lamotrigine, levetiracetam, topiramate, and zonisamide) are also available. These AEDs do not appear to have a common mechanism of action in that both inhibitory gamma-aminobutyric acid (GABA; e.g., clobazam, clonazepam, and valproate) and excitatory glutamate (e.g., lamotrigine and topiramate) mechanisms are involved. Ethosuximide primarily acts by blocking T-type voltage-gated calcium channels in thalamic neurones while topiramate and zonisamide have multiple mechanisms of action. In contrast, levetiracetam is unique in that it may act via a specific binding site in the brain. In terms of their pharmacokinetic characteristics, all eight AEDs are rapidly absorbed after oral ingestion with peak blood concentration being achieved within 1-4 hours. Bioavailability is 100% with the exception clonazepam (90%) and topiramate (81-95%). Plasma protein binding is variable with valproate (90%), clobazam (85%) and clonazepam (86%) showing substantial binding, lamotrigine (55%) and zonisamide (50%) intermediate binding, and levetiracetam (0%), ethosuximide (0%) and topiramate (10%) being minimally bound. However, the binding by zonisamide is complicated by its binding to erythrocytes as well as albumin. All AEDs, with the exception of lamotrigine and levetiracetam, undergo elimination as a result of extensive metabolism by hepatic cytochrome P450 enzymes, which are highly amenable to induction and inhibition by other drugs and therefore susceptible to pharmacokinetic interactions. Lamotrigine metabolism is via hepatic glucuronidation, a process that is also susceptible to induction and inhibition by concurrent drugs. Levetiracetam is minimally metabolized (by hydrolysis in blood), is excreted predominantly unchanged in urine, and to date has not been associated with any clinically significant pharmacokinetic interactions. Using a semiquantitative pharmacokinetic rating system, based on 16 pharmacokinetic characteristics, a direct comparison between AEDs is possible. Thus valproic acid, regarded as the drug of first choice in the treatment of IGEs, rates lowest with respect to favorable pharmacokinetic characteristics, mostly because of its nonlinear pharmacokinetics, extensive hepatic metabolism, and its high propensity to interact both with other AEDs and non-AEDs. Levetiracetam rates highest with topiramate in second place.

Anticonvulsants↗

PubMed2005

Subcortical nuclei volumetry in idiopathic generalized epilepsy.

PURPOSE: The exact anatomic and neurophysiologic correlates of idiopathic generalized epilepsy (IGE) in humans are still not well understood, although the thalamus has frequently been invoked as the crucial structure in the generation of primary generalized seizures. The few in vivo magnetic resonance (MR)-based studies in IGE patients suggest an altered cortical/subcortical gray matter ratio, but with no evidence of structural alterations of the thalamus. In this study, we sought to determine the volumes of the other subcortical structures. METHODS: The volumes of the caudate nucleus, putamen, pallidum as well as the thalamus were each determined in both hemispheres in 11 patients with various IGE syndromes, normalized for whole-brain volumes and then compared with 15 age-matched controls. RESULTS: No differences were noted in thalamic volumes, confirming previous reports. However, smaller subcortical volumes were noted in the IGE patients (p < 0.009), mainly due to smaller putamen bilaterally (p < or = 0.015). CONCLUSIONS: It is speculated that the presence of discrete frontal dysfunction, as noted in neuropsychological studies in IGE patients, indirectly supports our results because the putamen projects predominantly to the frontal cortex. Larger studies with more homogeneous patient populations are needed to determine the robustness of these findings and whether they are specific for particular IGE syndromes.

Adult↗

PubMedDate not supplied

Determinants of IQ profile in children with idiopathic generalized epilepsy.

To determine the IQ profile of children with epilepsy and the influence of various epilepsy-related variables on IQ scores, we studied 50 children with idiopathic generalized epilepsy of > 1-year duration, 25 of their siblings, and 30 healthy controls. IQ assessments were made with Malin's Indian modification of the Wechsler Intelligence Scale for Children. The mean +/- SD IQ scores of children with epilepsy (85.6 +/- 12) and their siblings (93.2 +/- 11) were significantly lower than those of the controls (101.6 +/- 9). The IQ scores of the children with epilepsy were also significantly lower than those of their siblings (p < 0.05). The IQ scores showed a significant correlation with socioeconomic status (SES) score (r = 0.33), a history of status epilepticus (r = -0.38), duration of seizure disorder (r = -0.31), and total number of seizures (r = -0.31). On multiple regression analysis, status epilepticus emerged as the most significant variable, accounting for 14% variance, followed by SES score (9% variance), duration of seizure disorder (6% variance), and sex of the child (5% variance). Genetic or environmental factors that probably lead to cognitive deficit in children with epilepsy and their siblings require further study.

Analysis of Variance↗

PubMedDate not supplied

The axial spasm--the predominant type of drop seizure in patients with secondary generalized epilepsy.

In 45 patients suffering from secondary generalized epilepsy, we have recorded 239 drop seizures both by radio-telemetered EEG/split-screen video taping and polygraphically. Twenty of these patients had pure tonic drop seizures. Nine patients each had myoclonic-atonic or pure atonic seizures, whereas seven had slow falls that occurred during gradually developing tonic or akinetic seizures. We term the pure tonic drop seizure "axial spasm." It consists of a uniform pattern of movement lasting from 0.5 to 0.8 s and leading to a specific bearing characterized by a moderate flexion of the hips, the upper trunk, and the head. The arms are almost always involved being abducted, elevated and in a semiflexed position. A fall is provoked by the rapidity and violence of the flexion in the hips. The spasms can occur independently (pure axial spasm) or in connection with other seizure manifestations (combined axial spasm). In pure spasms, no disturbance of consciousness and no significant EEG changes--apart from a slight attentuation--are seen. In the combined axial spasms, distinct epileptic phenomena, in close connection with the axial spasms, can be observed, appearing either in the postspasm phase or in both the pre- and the afterphases. The prephase consists always of an absence and spike-and-wave activity. The onset of the spasm coincides with the last generalized spike, which is followed by a biphasic high-voltage slow wave. In the afterphases, various seizure patterns can be seen; quite characteristic are arrest states during which the patients are completely immobile and take up a postural-like or athetoid position. Almost as frequent are absences or absence-like states and tonic seizures. The afterphase can be compounded by two or three of these seizure patterns, the most common sequence of events in these cases being tonic--arrest state--absence. From the clinical and neurophysiological points of view, axial spasms can be regarded as a more mature form of infantile spasms. Clinical and experimental findings suppose a brainstem origin.

Adolescent↗

PubMed2005

Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy.

PURPOSE: Quantitative trait loci (QTL) mapping in mice revealed a seizure-related QTL (Szs1), for which the inward-rectifying potassium channel Kcnj10 is the most compelling candidate gene. Association analysis of the human KCNJ10 gene identified a common KCNJ10 missense variation (Arg271Cys) that influences susceptibility to focal and generalized epilepsies. The present replication study tested the initial finding that the KCNJ10 Cys271 allele is associated with seizure resistance to common syndromes of idiopathic generalized epilepsy (IGE). METHODS: The study sample comprised 563 German IGE patients and 660 healthy population controls. To search for seizure type-specific effects, two IGE subgroups were formed, comprising 258 IGE patients with typical absences (IAE group) and 218 patients with juvenile myoclonic epilepsy (JME group). A TaqMan nuclease assay was used to genotype the KCNJ10 single nucleotide polymorphism c.1037C > T (dbSNP: rs1130183) that alters amino acid at position 271 from arginine to cysteine. RESULTS: Replication analysis revealed a significant decrease of the Cys271 allele frequency in 446 IGE patients compared to controls (chi2 = 3.52, d.f. = 1, P = 0.030, one-sided; OR(Cys271+) = 0.69; 95% CI: 0.50-0.95). Among the IGE subgroups, lack of the Cys271 allele was accentuated in the JME group (chi2 = 5.20, d.f. = 1, P = 0.011, one-sided). CONCLUSION: Our results support previous evidence that the common KCNJ10 Arg271Cys missense variation influences seizure susceptibility of common IGE syndromes.

Alleles↗

PubMed2005

Syndromes of idiopathic generalized epilepsies not recognized by the International League Against Epilepsy.

This chapter assesses probable epileptic syndromes within the idiopathic generalized epilepsies (IGE) that have not yet been recognized by the International League Against Epilepsy (ILAE). Jeavons syndrome, a purely reflex IGE that predominantly manifests with eyelid myoclonia and electroencephalogram (EEG) abnormalities on eye closure, is the most distinct and undisputed of the syndromes. Another is autosomal-dominant cortical tremor, myoclonus, and epilepsy, a purely monogenic disorder that has been documented in numerous reports, mainly from Japan and Italy. Perioral myclonia with absences is certainly a seizure type that may constitute an IGE syndrome when it is associated with a number of other clinical and EEG manifestations. Similarly, many patients suffer for years from phantom absences, a type of mild absence, before a first generalized tonic-clonic seizure that usually occurs in adulthood. Both perioral myoclonia with absences and phantom absences are clinically significant because they are probably lifelong and are associated with a very high incidence (around 50%) of absence status epilepticus that may escape diagnosis and appropriate treatment. The position of early childhood IGE, which manifests mainly with typical absence seizures that are distinctly different from childhood absence epilepsy and other recognized IGE syndromes, is less clear. The prevalence of these syndromes is significant. Their identification allows better clinical management and is important for genetic research and counselling. In addition, their recognition permits application of exclusion criteria for a more purified definition and a better understanding of the true boundaries of the other IGE syndromes already accepted by the ILAE.

Child↗

PubMed2005

Coexistence of focal and idiopathic generalized epilepsy in the same patient population.

PURPOSE: To review the clinical, electrographic, radiological, and pathological findings of patients with coexistent idiopathic generalized and partial epilepsy syndromes. METHODS: We performed a medical record review and a phone interview with all patients hospitalized to the Cleveland Clinic epilepsy monitoring unit (EMU) between 1992 and 2002 who fulfilled clinical and EEG criteria of coexistent partial and generalized epilepsy syndromes. RESULTS: Seven patients were identified. Two (29%) were men with a mean age of 26 years. Four had a history of febrile seizures. Family history was positive in five. Mean duration of the generalized epilepsy syndrome was 11 years, and of the focal epilepsy 18 years. An equal number of patients developed focal versus generalized epilepsy first. Interictal EEG activity was predominantly generalized. Four had video-EEG documentation of both types of seizures. In the rest, only focal seizures were recorded but interictal activity strongly suggested a coexistent generalized epilepsy. MRI showed hippocampal atrophy in all, and hippocampal dysplasia in three. Five patients had PET imaging, all with hypometabolism in areas corresponding to the ictal onset on EEG. Four patients underwent epilepsy surgery with good surgical outcome and pathological confirmation of hippocampal sclerosis in all. CONCLUSION: We found a 0.2% incidence of coexistent focal and primary generalized epilepsy. Febrile seizures and a positive family history were common. Good seizure control was achieved after temporal lobectomy, even when interictal generalized activity predominated.

Adolescent↗

PubMed2004

The coexistence of idiopathic generalized epilepsy and partial epilepsy.

PURPOSE: To describe the clinical, EEG, and imaging data of a series of patients with features of both idiopathic generalized epilepsy (IGE) and partial epilepsy. METHODS: A computerized database of all patients attending the regional epilepsy clinic was used to identify all patients with IGE. Case notes were reviewed, and cases with clinical evidence of co-existing partial epilepsy identified. RESULTS: Nine cases with clinical features of a partial and generalized-onset epilepsy and with electrophysiological evidence of IGE are presented. This represented <1% of the overall IGE population in the clinic. Five (55.6%) patients are currently in remission, with successful epilepsy surgery in one patient. CONCLUSIONS: The coexistence of IGE and partial epilepsy is uncommon, and if appropriate treatment with a broad-spectrum antiepileptic drug is given, then the prognosis can be good. Surgery should be considered for those cases with medically intractable partial-onset seizures as part of this syndrome.

Adult↗

PubMed2003

EEG in adult-onset idiopathic generalized epilepsy.

PURPOSE: It remains controversial whether adult-onset idiopathic generalized epilepsy (IGE) is a distinct syndrome or a continuum among IGE syndromes. EEG is the only known biologic marker of IGE and helps differentiate many of its classic subsyndromes. In this study, we looked for the differences in the EEG findings of IGE of classic adolescent onset versus adult onset that may suggest syndromic heterogeneity. METHODS: Seventy-six patients (47 adolescent-onset IGE, 29 adult-onset IGE) with a clinical and EEG diagnosis of IGE were included. We defined IGE with age at onset of 11-20 years as adolescent-onset IGE and age at onset of 20 years or after as adult-onset IGE. Patients with first-decade onset of seizures, delayed EEGs, and no EEG available for review were excluded. The first EEG was performed within 24 h of the seizure, and if negative, a sleep-deprived EEG was done. All EEGs were reviewed in detail with respect to the background activity and the generalized spike-wave (GSW) characteristic. RESULTS: EEGs (87; 56 adolescent-onset IGE, 31 adult-onset IGE) were systematically reviewed. Background was normal in all patients. The morphology, amplitude, duration, frequency, occurrence, or activation of the GSW pattern did not differ between these two groups. CONCLUSIONS: No differences of EEG features were found between the classic adolescent-onset and the adult-onset IGE. This supports the hypothesis that they share common biologic determinants and exist along a life-long age spectrum of classic IGE.

Adolescent↗

PubMed2001

The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy.

We tested the hypothesis that genetic variation in the human sodium channel gene SCN2A confers liability to idiopathic generalized epilepsy (IGE). We performed a systematic search for mutations in 46 familial IGE cases and detected three novel polymorphisms, however, allele frequencies did not differ significantly between patients and controls. A rare mutation (R1918H) was identified in one patient but was absent in one further affected family member. Thus, our results do not suggest a major role of SCN2A in the etiology of IGE.

Alleles↗

PubMed1998

Psychopathology in pediatric complex partial and primary generalized epilepsy.

Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.

Adolescent↗

PubMed1999

[Effect of awakening and sleep deprivation in triggering idiopathic generalized epilepsy].

The facilitating effect of awakening and sleep deprivation on seizure production and EEG abnormalities is characteristic of idiopathic generalized epilepsies (IGE). This effect is particularly patent in awakening epilepsy. Paroxysmal events occurring in non-REM sleep, related to spindle production during transitional periods or awakening are characteristic of IGE. Because IGEs are particularly sensitive to sleep, sleep deprivation, and awakening, the association of these three conditions is particularly helpful in exploration protocols, especially when no wakefulness abnormalities are seen on the EEG. These observations in IGE suggest a dysfunction of awakening control systems. Awakening epilepsies may be differentiated from sleep-induced seizures observed in other IGE and in partial epilepsies.

Cerebral Cortex↗

PubMed1983

[Effect of single-stage stereotaxic destruction of Forel's field H on neurologic functions and the structure of paroxysms in patients with generalized epilepsy].

The structure and frequency of epileptic paroxysms and neurologic symptoms were analyzed in nine patients with generalized epilepsy in the early period after one-stage stereotactic Forel-H-destructions. The inhibitory influence of the operation on epileptic activity in this period is demonstrated and the variants of neurologic deficit are depicted. The early post-stereotactic investigations are shown to be promising for improving the efficacy of surgical treatment of generalized epilepsy and for gaining a better insight into Forel-H-functions.

Adolescent↗

PubMed2003

Acute management of seizures in the syndromes of idiopathic generalized epilepsies.

Three of the seizure types (myoclonic, absence, and generalized tonic-clonic) and syndromes associated with idiopathic generalized or genetic epilepsies can present an acute status epilepticus picture that requires acute therapy. These are not the usual seizures observed in status epilepticus because most of these patients have secondary generalized or symptomatic generalized convulsive seizures. In this review, I discuss the unique presentation and treatment options for the acute management of seizures in the syndromes of idiopathic generalized epilepsy (IGE), with special emphasis on the seizures of status epilepticus, which persist over time or occur in a series without recovery of consciousness.

Acute Disease↗

PubMed2001

Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation.

BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant syndrome characterized by febrile seizures (FS) and a variety of afebrile generalized seizure types. GEFS+ has previously been linked to mutations in two genes encoding the voltage-gated sodium channel alpha-subunit (SCN1A) and beta1-subunit (SCN1B). We studied a large family with FS and partial as well as generalized seizure types. METHODS: All but two living affected family members were interviewed and examined. Information on deceased affected family members was sought. EEG for 11 affected family members and one unaffected family member were obtained. Genetic linkage analysis and mutation screening of SCN1A were performed on blood samples from 16 affected individuals and their first-degree relatives. RESULTS: There were 27 affected family members; 18 were alive at the time of the study. All affected family members had FS; seven had FS only, and 19 also had afebrile seizures. Eleven individuals continued to have FS beyond 6 years of age. FS were complex in 12 family members, usually with prolonged duration. The index patient had right temporal lobe epilepsy and hippocampal sclerosis. Four other patients had strong historical evidence of temporal lobe epilepsy, and three others had nonlocalizing evidence of partial epilepsy. Pedigree analysis indicated autosomal dominant transmission. All affected individuals who were tested and one asymptomatic individual had a sodium channel mutation of SCN1A, an A-->C transversion at nucleotide 3809 resulting in the substitution of lysine 1270 by threonine in the D3/S2 segment (designated as K1270T). CONCLUSIONS: Our findings indicate that partial epilepsy preceded by FS can be associated with sodium channel mutations and may represent a variant of GEFS+.

Adolescent↗

PubMed1999

Coexistence of temporal lobe and idiopathic generalized epilepsies.

OBJECTIVE: To assess the interrelation of idiopathic generalized epilepsy (IGE) and temporal lobe epilepsy (TLE) when they coexist in the same patient. METHODS: The authors reviewed the electroclinical features of 350 consecutive patients who had temporal resection between 1975 and 1997 at the Maudsley and King's College Hospitals, London. RESULTS: Two patients had the unusual combination of TLE and IGE (0.57%). In the first, the clinical onset of juvenile myoclonic epilepsy followed the surgical resolution of his partial seizures but had been heralded for at least 5 years by subclinical spontaneous and photically induced generalized spike-wave discharges. In the second, TLE and juvenile absence epilepsy had a long parallel course before surgery. After surgery he had no further partial seizures. CONCLUSION: These cases suggest that when an idiopathic absence or myoclonic syndrome manifests in a patient with symptomatic TLE, the phenotype may not be a merged syndrome. Rather, the two conditions can retain their inherent electroclinical profile, responsiveness to treatment, and prognosis.

Adult↗

PubMed2001

Measures of psychopathology in children with complex partial seizures and primary generalized epilepsy with absence.

OBJECTIVE: This investigation examined psychopathology in 48 children with complex partial seizures (CPS), 39 children with primary generalized epilepsy with absence (PGE), and 59 nonepileptic children, aged 5 to 16 years, by comparing the Child Behavior Checklist (CBCL) and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). METHOD: The CBCL was completed by parents and the K-SADS was administered to both parent and child. RESULTS: The CBCL identified psychopathology in 26% and the K-SADS in 51% of the CPS and PGE patients (kappa = 0.32). The CPS and PGE groups had significantly higher mean CBCL scores, as well as higher rates of psychiatric diagnoses and symptoms of psychopathology, compared with the nonepileptic group. However, the CPS and PGE groups did not differ in these measures. Within each patient group, Full Scale IQ, but not seizure control, was associated with these measures of psychopathology. CONCLUSION: These findings suggest that the K-SADS identifies more children with psychopathology than the CBCL in children with CPS and PGE.

Adolescent↗

PubMed1995

Wavelength specificity of photoparoxysmal responses in idiopathic generalized epilepsy.

Using optic filters, we analyzed the wave-length specificity of photoparoxysmal responses (PPR) in photosensitive patients with idiopathic generalized epilepsy (IGE). We specified the wavelength spectrum approximately 700 nm (660-720 nm) as the only visible spectrum essential for eliciting PPR in some normal trichromat IGE patients and showed that any flashing lights containing this essential wavelength spectrum could elicit PPR independent of the number of stimulated cones. Absorption of the wavelength spectrum approximately 700 nm by optic filters eliminated PPR in normal trichromat IGE patients. In an IGE patient with deuteranomaly, intermittent flashing lights containing a part of the wavelength spectrum from 580 to 700 nm elicited PPR. These data suggest a new interpretation of wavelength specificity of PPR: Flashing lights containing the wavelength spectrum that does not produce antagonistic cone interactions at the level of retinal ganglion cells can elicit PPR in some photosensitive IGE patients.

Adolescent↗