RESUMO
OBJECTIVE: The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development. METHODS: A systematic review of the literature (1985-2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology [AAN], ILAE) were also searched to minimize publication bias. Two independent reviewers screened abstracts, reviewed full text articles, and performed data abstraction. Descriptive statistics and a meta-analysis were generated. RESULTS: The search identified 10,926 abstracts. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug-resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1-7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 ± 1.05 [SD]). SIGNIFICANCE: We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future epilepsy-related guidelines.
Assuntos
Epilepsia/terapia , Guias de Prática Clínica como Assunto , Comitês Consultivos/normas , Comitês Consultivos/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Medicina Baseada em Evidências , Humanos , Sociedades MédicasRESUMO
The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgi1 is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies.
Assuntos
Doenças Auditivas Centrais/genética , Epilepsia/genética , Genes Dominantes , Mutação , Proteínas/genética , Animais , Doenças Auditivas Centrais/complicações , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 10 , DNA , Epilepsia/complicações , Feminino , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: Depression is the most common comorbid condition in epilepsy. The cause of this comorbidity is unknown, and could involve psychosocial consequences of epilepsy, treatment side effects, seizure manifestations, or common neurobiologic mechanisms. One hypothesis of particular interest is a shared genetic susceptibility to epilepsy and depression. We tested this hypothesis by studying depressive symptoms in families with an identified genetic form of epilepsy: autosomal dominant partial epilepsy with auditory features caused by mutations in the leucine-rich, glioma inactivated 1 gene (LGI1). METHODS: A standardized depression screen was administered to 94 individuals from 11 families with mutations in LGI1, including 38 mutation carriers with epilepsy (AC), 11 clinically unaffected mutation carriers (UC), and 45 noncarriers (NC). RESULTS: Current depressive symptom scores were significantly higher in AC than in NC, an association that remained after excluding depressive symptoms that appeared likely to be caused by antiepileptic medication use. However, scores did not differ between UC and NC. DISCUSSION: Although LGI1 mutation carriers who were clinically affected with epilepsy had increased depressive symptoms, mutation carriers without epilepsy did not. These findings suggest that the increase in depressive symptoms in affected individuals from these families is related to epilepsy or its treatment rather than to LGI1 mutations per se.
Assuntos
Transtorno Depressivo Maior/epidemiologia , Epilepsia/genética , Heterozigoto , Mutação/genética , Proteínas/genética , Adulto , Idade de Início , Comorbidade , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/epidemiologia , Epilepsias Parciais/genética , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Feminino , Nível de Saúde , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Linhagem , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
PURPOSE: To estimate the prevalence of epilepsy in a racially and ethnically diverse neighborhood in New York City. METHODS: We used random-digit dialing to identify people with a history of epilepsy. We estimated the prevalence of active epilepsy and lifetime epilepsy. RESULTS: The age-adjusted prevalence of active epilepsy was 5.0 per 1000, and that of lifetime epilepsy was 5.9 per 1000. Prevalence appeared higher in Hispanics (active prevalence: 6.3 per 1000; lifetime prevalence: 7.5 per 1000) than in non-Hispanics (active prevalence: 4.1 per 1000; lifetime prevalence: 4.7 per 1000). Blacks appeared to have a lower prevalence of active epilepsy (5.2 per 1000) than whites (5.9 per 1000), but a higher lifetime prevalence (7.5 per 1000 vs. 5.9 per 1000). Ethnic and racial differences in access to epilepsy care were evident both in terms of drug treatment and use of emergency departments for care. CONCLUSIONS: The prevalence of epilepsy in this predominantly minority urban community is similar to that reported in other contemporary studies. Less access to health care for black and Hispanic respondents, compared with white respondents, may have influenced self-reported active epilepsy prevalence estimates since the definition includes recent use of antiseizure medication.
Assuntos
Epilepsia/epidemiologia , Etnicidade , Adulto , Fatores Etários , Interpretação Estatística de Dados , Atenção à Saúde , Educação , Feminino , Inquéritos Epidemiológicos , Humanos , Renda , Masculino , Cidade de Nova Iorque/epidemiologia , Características de Residência , Classe Social , Inquéritos e Questionários , TelefoneRESUMO
Ellen Grass was a remarkable woman whose efforts on behalf of neurophysiology, epilepsy, and physiological technology contributed importantly to the development of neuroscience in the United States during the middle third of the 20th century. She initially provided an important link between a remarkable group of Harvard physiologists and her husband, Albert, a brilliant engineer whose innovative equipment played a critical role in accelerating advances in neurophysiology and, later, EEG and epilepsy. Mrs. Grass herself observed and personally facilitated much of the clinical and basic neuroscience research during this period, when the modern framework for a scientific understanding of epilepsy and EEG was established. She also supported the development of professional societies relevant to these areas, including ASET, the American EEG Society, the American Epilepsy Society, and the Epilepsy Foundation of America.
Assuntos
Eletroencefalografia/história , Epilepsia/diagnóstico , Epilepsia/história , Neurofisiologia/história , História do Século XX , HumanosAssuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Adulto , Anticonvulsivantes/efeitos adversos , Transtorno Depressivo/complicações , Diagnóstico Diferencial , Interações Medicamentosas , Epilepsia/diagnóstico , Epilepsia/psicologia , Feminino , Humanos , Exame Neurológico , Guias de Prática Clínica como AssuntoRESUMO
Histological analysis of hippocampi removed en bloc during surgical treatment of temporal lobe epilepsy revealed a subgroup of patients with bulbous expansions of the CA1 pyramidal cell/subicular layers that were consistently accompanied by "tectonic" invaginations of the adjacent dentate gyrus. Most hippocampi containing the CA1/subicular anomaly and the tectonically deformed dentate gyrus exhibited minor cell loss compared to hippocampi with typical hippocampal sclerosis, and retrospective analysis revealed that conventional imaging methods usually failed to detect subtle hippocampal atrophy or abnormal signal characteristics in patients with this anomaly. Cells within the anomaly exhibited the spherical appearance of undifferentiated pyramidal layer neurons, and were immunopositive for the neuronal marker NeuN. Immunostaining for the synaptic marker beta-synuclein suggested abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly, but not in unaffected areas of the same specimens. Despite differences in the extent of neuronal loss between patients with hippocampal sclerosis and those with the CA1/subicular anomaly, the incidence of antecedent febrile seizures was similar in both groups. In a comparison group of hippocampi obtained at autopsy, structural irregularities were evident, but were consistently less disruptive to hippocampal architecture than the anomalies observed in epilepsy patients. We hypothesize that developmental malformation of the CA1 pyramidal cell/subicular layers may adversely influence the subsequent development of the adjacent dentate gyrus, and may render temporal lobe structures hyperexcitable and more vulnerable to relatively innocuous seizures and injuries. Thus, these presumably developmental hippocampal anomalies may serve as substrates for early febrile seizures and subsequent epilepsy.
Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/anormalidades , Hipocampo/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia do Lobo Temporal/cirurgia , Feminino , Hipocampo/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Indústria Farmacêutica/tendências , Neurologia/tendências , Política Organizacional , Sociedades Médicas , Academias e Institutos/organização & administração , Academias e Institutos/normas , Relatórios Anuais como Assunto , Indústria Farmacêutica/organização & administração , Indústria Farmacêutica/normas , Humanos , Neurologia/organização & administração , Neurologia/normasAssuntos
Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/farmacocinética , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Epilepsia/metabolismo , HumanosAssuntos
Estimulação Encefálica Profunda/métodos , Neurologia/métodos , Psiquiatria/métodos , Estimulação Magnética Transcraniana/métodos , Estimulação Encefálica Profunda/tendências , Humanos , Transtornos Mentais/terapia , Doenças do Sistema Nervoso/terapia , Neurologia/tendências , Psiquiatria/tendências , Estimulação Magnética Transcraniana/tendênciasRESUMO
PURPOSE: Determining the existence of syndrome-specific genetic factors in epilepsy is essential for phenotype definition in genetic linkage studies, and informs research on basic mechanisms. Analysis of concordance of epilepsy syndromes in families has been used to assess shared versus distinct genetic influences on generalized epilepsy (GE) and localization-related epilepsy (LRE). However, it is unclear how the results should be interpreted in relation to specific genetic hypotheses. METHODS: To assess evidence for distinct genetic influences on GE and LRE, we examined concordance of GE and LRE in 63 families containing multiple individuals with idiopathic or cryptogenic epilepsy, drawn from the Epilepsy Family Study of Columbia University. To control for the number of concordant families expected by chance, we used a permutation test to compare the observed number with the number expected from the distribution of individuals with GE and LRE in the study families. RESULTS: Of the families, 62% were concordant for epilepsy type, and 38% were discordant. In all analyses, the proportion of concordant families was significantly greater than expected. CONCLUSIONS: This suggests that some genetic influences predispose specifically to either GE or LRE. Because of the ascertainment bias resulting from the selection of families containing multiple individuals with epilepsy, we could not test whether there are also shared genetic influences on these two epilepsy subtypes. Population-based studies will be needed to explore these results further.
Assuntos
Epilepsias Parciais/genética , Epilepsia Generalizada/genética , Ligação Genética/genética , Epilepsias Parciais/classificação , Epilepsias Parciais/epidemiologia , Epilepsia Generalizada/classificação , Epilepsia Generalizada/epidemiologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Fatores de RiscoRESUMO
PURPOSE: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. METHODS: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. RESULTS: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (theta=0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. CONCLUSIONS: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway.