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Generalized Epilepsy (generalized + epilepsy)
Kinds of Generalized Epilepsy Selected AbstractsWorkshop on Idiopathic Generalized Epilepsies: Bridging basic science and clinical research (October 3,6, 2007; Antalya, Turkey)EPILEPSIA, Issue 11 2008Edward H. Bertram First page of article [source] Idiopathic Generalized Epilepsies: A Review and Modern ApproachEPILEPSIA, Issue 2005Chrysostomos P. Panayiotopoulos M.D., Ph.D. First page of article [source] Historical Aspects of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Peter Wolf Summary:, Early in these proceedings, the origin of the three terms in the title, "idiopathic generalized epilepsy," is discussed with respect to their significance over time, and typical misunderstandings. In the mid-20th century, a rather chaotic use of a multitude of often loosely defined terms had developed, which increasingly became an obstacle to a meaningful international discussion. The International League against Epilepsy (ILAE) took the initiative to develop an internationally accepted terminology with a classification system consisting of a classification of seizures (1981) and a classification of syndromes (1989). The Idiopathic Generalized Epilepsies are one of its four major groups emerging from a double dichotomy of generalized versus localization-related and idiopathic versus symptomatic. The inclusion of biologic aspects such as syndrome-specific ages of onset ("age-related syndromes") or syndrome-specific relations of seizure occurrence to the sleep,wake cycle ("Epilepsy with Grand Mal on Awaking") meant that the syndrome classification merged the more biological views of the German school with the more neurophysiological ones of the French. Apart from establishing a common international language concerning epilepsy, the International Classification of Epilepsies and Epileptic Syndromes became an important stimulator of research, especially concerning the idiopathic epilepsies. In particular, genetic and functional imaging investigations aim at a better understanding of these conditions. It is now understood that most idiopathic syndromes have a,sometimes complex,genetic background, but we are also becoming aware of the inappropriateness of the time-honored term "generalized" and part of our dichotomies. Both localization-related and "generalized" idiopathic epilepsies seem to share a principle of ictogenesis based on functional anatomic pathogenic networks, and we seem to move toward understanding them as functional system disorders of the brain. [source] Symptomatic Epilepsies Imitating Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Hirokazu Oguni Summary:, The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1,4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs. [source] Evidence-based Treatment of Idiopathic Generalized Epilepsies with Older Antiepileptic DrugsEPILEPSIA, Issue 2005Nikolas Hitiris Summary:, Older antiepileptic drugs continue to play a major role in the treatment of the idiopathic generalized epilepsies. Comparative studies of ethosuximide and valproate have demonstrated equivalence in the treatment of childhood absence epilepsy. Valproate can be regarded as the recommended first-line treatment for juvenile myoclonic epilepsy based on case series reports. Studies in patients with generalized tonic-clonic seizures have not separated out idiopathic from secondary generalized events. Treatment for the other idiopathic generalized epilepsy syndromes lacks evidence other than a few case reports and diverse expert opinion. Further randomized controlled trials of older antiepileptic drugs are recommended to solidify the evidence-based treatment of the idiopathic generalized epilepsies. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Biparental Inheritance in Idiopathic Generalized EpilepsyEPILEPSIA, Issue 10 2004An C. Jansen No abstract is available for this article. [source] Genetic Architecture of Idiopathic Generalized Epilepsy: Clinical Genetic Analysis of 55 Multiplex FamiliesEPILEPSIA, Issue 5 2004Carla Marini Summary: Purpose: In families with idiopathic generalized epilepsy (IGE), multiple IGE subsyndromes may occur. We performed a genetic study of IGE families to clarify the genetic relation of the IGE subsyndromes and to improve understanding of the mode(s) of inheritance. Methods: Clinical and genealogic data were obtained on probands with IGE and family members with a history of seizures. Families were grouped according to the probands' IGE subsyndrome: childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and IGE with tonic,clonic seizures only (IGE-TCS). The subsyndromes in the relatives were analyzed. Mutations in genes encoding ,1 and ,2 ,-aminobutyric acid (GABA)-receptor subunits, ,1 and ,1 sodium channel subunits, and the chloride channel CLC-2 were sought. Results: Fifty-five families were studied. 122 (13%) of 937 first- and second-degree relatives had seizures. Phenotypic concordance within families of CAE and JME probands was 28 and 27%, respectively. JAE and IGE-TCS families had a much lower concordance (10 and 13%), and in the JAE group, 31% of relatives had CAE. JME was rare among affected relatives of CAE and JAE probands and vice versa. Mothers were more frequently affected than fathers. No GABA-receptor or sodium or chloride channel gene mutations were identified. Conclusions: The clinical genetic analysis of this set of families suggests that CAE and JAE share a close genetic relation, whereas JME is a more distinct entity. Febrile seizures and epilepsy with unclassified tonic,clonic seizures were frequent in affected relatives of all IGE individuals, perhaps representing a nonspecific susceptibility to seizures. A maternal effect also was seen. Our findings are consistent with an oligogenic model of inheritance. [source] An Xp; Yq Translocation Causing a Novel Contiguous Gene Syndrome in Brothers with Generalized Epilepsy, Ichthyosis, and Attention DeficitsEPILEPSIA, Issue 12 2003Michael J. Doherty Summary:,Purpose: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri,Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome. Methods: Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. Results: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat. Conclusions: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes. [source] Two Novel SCN1A Missense Mutations in Generalized Epilepsy with Febrile Seizures PlusEPILEPSIA, Issue 9 2003Grazia Annesi No abstract is available for this article. [source] Mild Generalized Epilepsy and Developmental Disorder Associated with Large Inv Dup(15)EPILEPSIA, Issue 9 2002Rosanna Chifari Summary: ,Purpose: Several studies attempted to clarify the genotype,phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup(15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader,Willi/Angelman region. We report two patients with inv dup(15) who, in spite of a large duplication, had a mild phenotype including adult-onset epilepsy. This report may help to define the milder spectrum of the syndrome. Methods: A 25-year-old girl with mild mental retardation had a 6-year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike,wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27-year-old man with mild mental retardation, had a 5-year history of rare generalized tonic,clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video-EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control. Results: Molecular analysis revealed a large inv dup15 in both patients. Conclusions: The discrepancy between the mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear-cut etiology. [source] Nonsymptomatic Generalized Epilepsy in Children Younger than Six Years: Excellent Prognosis, but Classification Should Be Reconsidered after Follow-up: The Dutch Study of Epilepsy in ChildhoodEPILEPSIA, Issue 7 2002C. M. Middeldorp Summary: ,Purpose: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy. Methods: Of the cohort of the Dutch Study of Epilepsy in Childhood (n = 466), all children younger than 6 years with a diagnosis of idiopathic (IGE) or cryptogenic (CGE) generalized epilepsy either at intake (n = 108) and/or after 2 years of follow-up (n = 102) were included. The number of reclassifications after 2 years was determined, and the reasons for reclassification were analyzed. All children receiving a diagnosis of IGE or CGE at 2 years were followed up for 5 years to study their outcome in terms of terminal remission (TR). Data on their level of intellectual functioning were collected at the start of this analysis. Results: The epilepsy syndrome was reclassified in 17 children. In 14 of them, the seizure type also was reclassified, and in three, the course of the epilepsy determined the new epilepsy type. Two other children had a reclassification of their seizure types without a change of the epilepsy type. Many children were categorized as having IGE not otherwise specified. In all probability, this is a heterogeneous group, containing patients with various epilepsy syndromes, with generalized tonic,clonic seizures as a common hallmark. Of the 102 children with IGE or CGE at 2 years of follow-up, 75% had a TR of >6 months after 2 years, and 85% a TR of ,1 year after 5 years. Conclusions: In a fair proportion of children with nonsymptomatic generalized epilepsy in this age group, it is not possible to classify firmly the epilepsy and/or the seizures immediately after the intake. Instead, they are reclassified during the course of the disease. This and the apparent heterogeneity of the category IGE not otherwise specified point to inherent drawbacks of the current International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The prognosis of IGE at this young age is generally excellent. [source] Genes and loci involved in febrile seizures and related epilepsy syndromes,HUMAN MUTATION, Issue 5 2006Dominique Audenaert Abstract Epilepsy is a paroxysmal disorder with a cumulative incidence of about 3%. About 13% of patients with epilepsy have a history of febrile seizures (FS). Generalized epilepsy with FS plus (GEFS+) is a familial epilepsy syndrome in which patients can have classic FS, FS that persist beyond the age of 5 years (i.e., FS+), and/or epilepsy. Both genetic and environmental factors have been shown to contribute to the pathogenesis of FS and GEFS+. During the past 10 years, molecular genetic studies have contributed a great deal to the identification of genetic factors involved in FS and GEFS+. In this study we aimed to provide a comprehensive review of currently known genes for FS and GEFS+, and the methods and approaches used to identify them. We also discuss the knowledge we currently have and hypotheses regarding the effect of the mutations on their respective protein functions. Hum Mutat 27(5), 391,401, 2006. © 2006 Wiley-Liss, Inc. [source] Nonepileptic Disorders Imitating Generalized Idiopathic EpilepsiesEPILEPSIA, Issue 2005Natalio Fejerman Summary:, Differential diagnosis between epileptic and nonepileptic paroxysmal disorders is fundamental not only to allow correct management of patients but also to avoid the burden of unnecessary antiepileptic medication. The focus of this chapter is limited to imitators of idiopathic generalized epilepsies (IGE) which are expressed through myoclonic, tonic,clonic, tonic, atonic, and absence seizures. Apparent losses of consciousness and drop attacks also have to be considered. Benign myoclonus of early infancy is the main nonepileptic disorder in the differential diagnosis of infantile spasms, but is not dealt with here because West syndrome is not an IGE. Hyperekplexia, metabolic disorders, hypnagogic myoclonus, and disturbed responsiveness caused by the use of drugs are listed in Table 1. Other conditions that may imitate more focal epileptic seizures are omitted. Benign neonatal sleep myoclonus, apnea and apparent life-threatening events in infants, cyanotic and pallid breath-holding spells, syncope, staring spells, psychogenic seizures, hyperventilation syndrome, and narcolepsy have been selected based on frequency or difficulties in differential diagnosis with the intention to cover the most conspicuous imitators of IGE in different ages. Table 1. Nonepileptic disorders imitating idiopathic generalized epilepsies [source] Symptomatic Epilepsies Imitating Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Hirokazu Oguni Summary:, The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1,4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs. [source] Evidence-based Treatment of Idiopathic Generalized Epilepsies with Older Antiepileptic DrugsEPILEPSIA, Issue 2005Nikolas Hitiris Summary:, Older antiepileptic drugs continue to play a major role in the treatment of the idiopathic generalized epilepsies. Comparative studies of ethosuximide and valproate have demonstrated equivalence in the treatment of childhood absence epilepsy. Valproate can be regarded as the recommended first-line treatment for juvenile myoclonic epilepsy based on case series reports. Studies in patients with generalized tonic-clonic seizures have not separated out idiopathic from secondary generalized events. Treatment for the other idiopathic generalized epilepsy syndromes lacks evidence other than a few case reports and diverse expert opinion. Further randomized controlled trials of older antiepileptic drugs are recommended to solidify the evidence-based treatment of the idiopathic generalized epilepsies. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Genital Automatisms: A Video-EEG Study in Patients with Medically Refractory SeizuresEPILEPSIA, Issue 7 2004Judith Dobesberger Summary:,Purpose: Genital automatisms (GAs) are rare clinical phenomena during or after epileptic seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The anatomic correlates of GAs have been discussed controversially. The aim of this investigation was to assess the localizing and lateralizing value of GAs. Methods: The authors studied 207 consecutive patients with intractable seizures referred to a University Hospital for presurgical evaluation between 1998 and 2002: 135 had temporal lobe epilepsy (TLE); 23, frontal lobe epilepsy (FLE); 29, generalized epilepsies (GEs); and 20 had extratemporal or multifocal epilepsy. Results: Twenty-three (11%) of 207 patients showed GAs in 42 (3%) of 1,299 seizures. GAs occurred significantly more often in men (17 of 93, 18%) than in women (six of 114, 5%; p = 0.0037). Twenty-one (16%) of 135 patients with TLE performed GAs, one (4%) of 23 with FLE and one (3%) of 29 with GE. GAs were associated with unilateral hand automatisms in 16 (70%) of 23 and with periictal urinary urge in five (22%) of 23. All patients had amnesia for the performance of GAs. Conclusions: GAs appear in the ictal or postictal period with impaired consciousness. Men exhibit GAs significantly more often than do women. GAs do not localize or lateralize per se, but may localize seizure onset in the presence of periictal urinary urge or unilateral hand automatisms. They show a tendency to occur more often in TLE. [source] Health-related Quality of Life of People with Epilepsy Compared with a General Reference Population: A Tunisian StudyEPILEPSIA, Issue 7 2004Hela Mrabet Summary:,Purpose: The goal of the study was to assess the health-related quality of life (HRQOL) of persons with epilepsy (PWE) by using the short form survey 36 (SF-36), to compare it with that of a control group and to detect factors influencing it. Methods: We collected clinical and demographic data and information on health status by using the Arabic translation of the SF-36 questionnaire from two groups: (a) 120 PWE consulting our outpatient clinic during a period of 4 months, and (b) 110 Tunisian citizens, representative of the Tunisian general population, as a control group. Results: The mean age of PWE group was 32.74 years, and 45.5% were men. Idiopathic generalized epilepsies were observed in 44.5% of cases, and symptomatic partial epilepsies, in 30%. The most commonly prescribed drug was sodium valproate (VPA). For the SF-36, PWE had lower scores than the control group for only three subscales: general health perception, mental health, and social functioning. Seizure frequency, time since last seizure, and the antiepileptic drug (AED) side effects were the most important variables influencing the HRQOL among PWE. Seizure-free adults have HRQOL levels comparable to those of the control group. Sociodemographic variables had no influence on the SF-36 subscales. Conclusions: HRQOL is impaired in Tunisian PWE. The influencing factors identified in this study differ from the previously published data. Several possible reasons such as family support and cultural and religious beliefs are proposed to explain these cross-cultural differences. A larger study should be conducted to verify such findings. [source] Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New-Onset Epilepsy: Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy SocietyEPILEPSIA, Issue 5 2004Jacqueline A. French Summary: Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. Results: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary. [source] Ictal EEG Patterns in Band HeterotopiaEPILEPSIA, Issue 4 2002Arthur C. Grant Summary: Band heterotopia (BH) or "double cortex" syndrome is a neuronal migration disorder resulting in a diffuse band of subcortical grey matter and variable abnormality of the overlying cortex. Patients with BH have a spectrum of psychomotor delay and seizures. Associated epileptic syndromes and interictal EEG findings have been described, but ictal EEG patterns are lacking. Methods: We describe the clinical, interictal, and ictal EEG findings in two girls with BH and intractable seizures. Results: Ictal EEG patterns correlated well with clinical seizure types, and did not have features unique to BH. Similarly, seizure behaviors and interictal EEG findings were typical of those seen in symptomatic generalized epilepsies. Conclusions: Despite evidence implicating the ectopic grey matter in seizure discharges, we conclude that seizure semiology and associated ictal EEG patterns in BH are no different from those seen in other causes of symptomatic generalized epilepsies. [source] New Insights into the Clinical Management of Partial EpilepsiesEPILEPSIA, Issue S5 2000Prof. Edouard Hirsch Summary The diagnosis, treatment, and prognosis of seizure disorders depend on the correct identification of epileptic syndromes. Partial epilepsies are heterogeneous and can be divided into idiopathic, cryptogenic, and symptomatic epilepsies. The most common of the idiopathic localization-related epilepsies is benign epilepsy with rolandic or centrotemporal spikes (BECTS). Seizures remain rare and the use of antiepileptic drug (AED) treatment in all patients does not appear justified. Children who present with some of the electroclinical characteristics of BECTS may also display severe unusual neurologic, neuropsychological, or atypical symptoms. In some cases, carbamazepine has been implicated as a triggering factor. Primary reading epilepsy and idiopathic occipital lobe epilepsies with photosensitivity are examples of an overlap between idiopathic localization-related and generalized epilepsies and respond well to sodium valproate. Autosomal dominant nocturnal frontal lobe epilepsy and benign familial infantile convulsions are recently described syndromes, differing in several ways from classical idiopathic localization-related epileptic syndromes. In cryptogenic or symptomatic epilepsy, the topography of the epileptogenic zone might influence drug efficacy. An individualized approach to AED selection, tailored to each patient's needs, should be used. Resistance of seizures to antiepileptic therapy may be due to diagnostic and/or treatment error or may be the result of noncompliance. Increasing the dosage, discontinuation or replacement of a drug, or addition of a second drug is indicated in truly resistant cases. The use of more than two AEDs rarely optimizes seizure control, and in some cases reduction of treatment may improve seizure control while lessening side effects. EEG-video assessment of patients with refractory epilepsy is important. Indications for and timing of epilepsy surgery should be reconsidered. Surgical therapy should probably be used more often and earlier than it is at present. [source] Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y2 receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Margaret J. Morris Abstract Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y-receptor subtype(s) on which NPY exerts this anti-absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90-min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype-selective agonists of Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu28,31]NPY24,36, 3 nmol), Y5 receptors [hPP1,17,Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y1 (BIBP3226, 20 nmol), Y2 (BIIE0246, 20 nmol) and Y5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1 - and Y5 -selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 agonist, while significant increases in food intake were seen following NPY and the other Y-subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation. [source] Molecular analysis of the A322D mutation in the GABAA receptor ,1 -subunit causing juvenile myoclonic epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Klaus Krampfl Abstract Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies. Although the mode of inheritance is usually complex, mutations in single genes have been shown to cause the disease in some families with autosomal dominant inheritance. The first mutation in a multigeneration JME family has been recently found in the ,1 -subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D. We further characterized the functional consequences of this mutation by coexpressing ,1 -, ,2 - and ,2 -subunits in human embryonic kidney (HEK293) cells. By using an ultrafast application system, mutant receptors have shown reduced macroscopic current amplitudes at saturating GABA concentrations and a highly reduced affinity to GABA compared to the wild-type (WT). Dose,response curves for current amplitudes, activation kinetics, and GABA-dependent desensitization parameters showed a parallel shift towards 30- to 40-fold higher GABA concentrations. Both deactivation and resensitization kinetics were considerably accelerated in mutant channels. In addition, mutant receptors labelled with enhanced green fluorescent protein (EGFP) were not integrated in the cell membrane, in contrast to WT receptors. Therefore, the A322D mutation leads to a severe loss-of-function of the human GABAA receptor by several mechanisms, including reduced surface expression, reduced GABA-sensitivity, and accelerated deactivation. These molecular defects could decrease and shorten the resulting inhibitory postsynaptic currents (IPSCs) in vivo, which can induce a hyperexcitability of the postsynaptic membrane and explain the occurrence of epileptic seizures. [source] Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsiesAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2001Diana Sobetzko Abstract Alterations of glycine receptor ,1 and , subunit genes have been associated with hypertonic motor disorders in both mice and humans. Mutations in genes encoding other ligand- and voltage-gated ion channels have been identified in rare monogenic forms of idiopathic generalized epilepsies (IGE). We tested the hypothesis that allelic variants of the glycine receptor subunit genes, GLRA3 and GLRB, both localized on chromosome 4q, confer susceptibility to common subtypes of IGE. Mutation screening was carried out in index patients of 14 IGE families. No pathogenic mutation was found, but two intronic polymorphisms were detected in the GLRB gene, and four intronic, three exonic, and one 3,-UTR polymorphisms were identified for the GLRA3 gene. Subsequent screening for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistical difference between a group of sporadic IGE patients (n,=,104) and a control group (n,=,141). The genotype frequencies for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistically significant difference between IGE patients (n,=,104) and an ethnically matched control group (n,=,141). Thus, no association between IGE and alterations in GLRA3 or GLRB genes could be detected, indicating that both genes do not play a major causative role in the epileptogenesis of common IGE subtypes. Still, these novel single nucleotide polymorphisms may be useful markers for candidate gene analyses of other disorders. © 2001 Wiley-Liss, Inc. [source] Idiopathic generalized epilepsies: a follow-up study in a single-centerACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010E. Kharazmi Kharazmi E, Peltola M, Fallah M, Keränen T, Peltola J. Idiopathic generalized epilepsies: a follow-up study in a single-center. Acta Neurol Scand: 122: 196,201. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To characterize adult patients with idiopathic generalized epilepsies (IGEs) with precise evaluation and to assess factors related to refractoriness. Materials and methods,,, Hospital records of all our patients with IGEs (n = 128) were evaluated in 2005 and followed-up until 2008. Results,,, In 2005, 76% of patients were 1-year seizure-free. Seizure freedom increased to 82% during the 3-year follow-up. Seizure freedom was not significantly associated with age, age at diagnosis, epilepsy duration, exposure to inappropriate initial antiepileptic drug (AED), or delay time between starting initial AED and appropriate AED. Women constituted 78% of patients with merely provoked seizures. In 58% of women with recent seizure, one to two avoidable precipitating factors, such as lack of sleep, alcohol, and forgetting to take AED, were observed. In 2008, all patients with no medication, 91% of monotherapy patients, 60% of patients on two AED, and 14% of patients on three AED were seizure-free. Conclusions,,, Most of patients with IGEs can be successfully treated with monotherapy. Refractory seizures in some patients may be because of avoidable factors, especially in young women. [source] The occurrence and characteristics of auras in a large epilepsy cohortACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009K. O. Nakken Objectives,,, Despite several studies, estimates of the frequency with which auras occur in conjunction with epilepsy continue to be imprecise. The aim of this study was to assess the occurrence and characteristics of auras in a large population-based epilepsy cohort. Materials and methods,,, Subjects with verified epilepsy were recruited from population-based twin registries in the USA, Denmark and Norway. Using a structured interview in which a list of auras was provided, subjects were asked about the warning symptoms preceding their epileptic attacks. Results,,, 31% of the total sample (n = 1897) and 39% of those with active epilepsy (n = 765) had experienced an aura. Six percent reported more than one type. Non-specified auras were most frequently reported (35%), followed by somatosensory (11%) and vertiginous (11%). While the majority of those reporting auras (59%) had focal epilepsies, auras of a mostly non-specific nature were experienced by 13% of those with generalized epilepsies. Conclusion,,, Auras serve an important purpose in that they may prevent seizure-related injuries and could provide an indication as to where the seizures originate. The occurrence of auras often is underestimated, especially in children and those with learning disabilities. [source] Role of valproate across the ages.ACTA NEUROLOGICA SCANDINAVICA, Issue 2006Treatment of epilepsy in adults A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability. [source] The management of idiopathic generalized epilepsiesACTA NEUROLOGICA SCANDINAVICA, Issue 2005S. R. Benbadis Idiopathic generalized epilepsies (IGEs) are a well defined group of epilepsies, with onset predominantly in childhood. Recent evidence suggests that IGEs may also be prevalent but under-diagnosed in adults. IGEs respond well to appropriate treatment and 80,90% of cases become fully controlled. However, correct identification of IGE and selection of a broad-spectrum antiepileptic drug (AED) is crucial if cases of ,pseudo-intractability' are to be avoided. Preliminary evidence suggests that some of the newer AEDs are broad spectrum and may offer advantages in the treatment of IGEs. There is strong evidence that childhood-, adolescent- and adult-onset IGEs share biologic determinants and are best viewed as a spectrum or continuum of conditions. The diagnosis of IGE, even as a group, is very important for proper management. [source] Topiramate overdose: A case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticusEPILEPSIA, Issue 6 2010Christian Brandt Summary We report the case of a 21-year-old man with idiopathic generalized epilepsy who ingested about 8,000 mg of topiramate (TPM) in a suicide attempt. On admission to the hospital he had a nonconvulsive status epilepticus and received 4 mg lorazepam i.v. He recovered rapidly despite an initial TPM concentration of 144.6 ,g/ml. To our knowledge, this is the first report of a patient who survived such a high TPM concentration. The case indicates that nonconvulsive status epilepticus could be a manifestation of TPM intoxication. [source] | |||||||||||||