Self-reported quality of life in pharmacoresistant temporal lobe epilepsy: correlation with clinical variables and memory evaluation.

AIM: This work explores the effects of clinical variables on self-reported quality of life (QoL) in pharmacoresistant temporal lobe epilepsy (TLE), correlating this information with results from the Quality of Life in Epilepsy questionnaire (QOLIE-31) and selective memory tests of the Barcelona Battery and the Rey-Osterrieth figure. METHODS: We retrospectively analysed the records of 60 TLE patients and correlated patient variables (e.g. gender, aetiology; mesial TLE with hippocampal sclerosis [HS] versus lesional TLE, side of ictal onset, age, age at onset, duration of epilepsy, seizure frequency, and use of AEDs) with selective memory test scores and self-reported QoL. RESULTS: Right ictal onset was associated with lower emotional well-being scores. MTLE-HS patients had lower QOLIE-31 scores for seizure worry, social function, overall QoL, energy/fatigue, cognitive function, and obtained a lower overall score, compared to those with lesional TLE. Older age at epilepsy onset was associated with worse emotional well-being, energy/fatigue, medication effects, and seizure worry outcomes. Higher seizure frequency and older age at time of evaluation were associated with lower cognitive function scores. Generalised seizures were associated with lower scores based on the variables: seizure worry, overall quality of life, emotional well-being, and cognitive function. Regarding memory tests, only visuospatial memory correlated positively with cognitive function score. Patients with MTLE-HS underwent evaluation for pharmacoresistant epilepsy, on average, 10 years later than those with lesional TLE. CONCLUSIONS: MTLE-HS, right-sided epileptogenic zone, late onset, and higher seizure frequency were associated with worse QoL. Objective testing revealed specific memory deficits that were not reflected in self-reported QoL scores.

Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a distinct form of idiopathic generalized epilepsy (IGE). One of the candidate regions for human JME has been mapped on chromosome band 6p11-p12 by linkage analyses and is termed EJM1 (MIM 254770). Recently, we reported the reduction of the EJM1 region to 3.5cM that contains 18 genes, the exclusion of three genes (LRRC1, GCLC, KIAA0057) by mutation analyses, and the identification of Myoclonin1/EFHC1 as the EJM1 gene. Here, we describe detailed physical and transcriptome maps of the 3.5cM EJM1 region, and detailed results of mutation analyses for the remained 14 genes (HELO1, GCMA, KIAA0936, FBXO9, GSTA3, GSTA4, PTD011, KIAA0576, LMPB1, IL17F, MCM3, PKHD1, KIAA0105, TFAP2B) in patients with JME. We identified 49 single nucleotide changes in eight genes. Twelve amino acid substitutions occurred in two genes, 11 silent mutations in seven genes, and 26 in the non-coding or intronic regions of seven genes. Twelve amino acid substitutions in the two genes (IL17F, PKHD1) were also observed in healthy control individuals or did not co-segregate with the disease phenotypes in other family members. Thus, the absence of significant and potentially functional mutations in the remaining 14 genes further supports the concept that Myoclonin1/EFHC1 is the EJM1 gene in chromosome 6p12.

Mutations in EFHC1 cause juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

Recent developments in the quest for myoclonic epilepsy genes.

Understanding the latest advances in the molecular genetics of the epilepsies is important, as it provides a basis for comprehending the new practice of epileptology. Epilepsies have traditionally been classified and subtyped on the basis of clinical and neurophysiologic concepts. However, the complexity and variability of phenotypes and overlapping clinical features limit the resolution of phenotype-based classification and confound epilepsy nosology. Identification of tightly linked epilepsy DNA markers and discovery of epilepsy-causing mutations provide a basis for refining the classification of epilepsies. Recent discoveries regarding the genetics surrounding certain epilepsy types (including Lafora's progressive myoclonic epilepsy, the severe myoclonic epilepsy of infancy of Dravet, and idiopathic generalized epilepsies) may be the beginning of a better understanding of how rare Mendelian epilepsy genes and their genetic architecture can explain some complexities of the common epilepsies.

Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.

Juvenile myoclonic epilepsy (JME) is one of the most frequent hereditary epilepsies characterized by myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Genetic studies have revealed four major chromosomal loci on 6p21.3, 6p11-12, 6q24, and 15q14 as candidate regions harboring genes responsible for JME. Previously we reported the region on 6p11-p12 (EJM1), and here we report the identification and mutational analysis of candidate genes for EJM1. One of those is a leucine-rich repeat-containing 1 (LRRC1) gene that is composed of 14 exons and codes for 524 amino acid residues. In Northern analysis, 7 kb transcripts of LRRC1 gene were detected in multiple tissues, most strongly, in heart, lung, and kidney. Mutation analysis of LRRC1 gene in 20 JME patients from ten families revealed one nucleotide substitution that lead to amino acid exchange (c.577 A>G; Ile193Val). This variation, however, did not co-segregate with the disease phenotype. We further performed mutational analyses of CLIC5, KIAA0057 and GCLC genes in or flank to the EJM1 region. These analyses did not provide any evidences that these genes are responsible for the JME phenotype, and suggested that these may not be the EJM1 gene.

Epilepsia: aspectos neurológicos, médicos y sociales / Epilepsy: neurological, medical and social aspects

Participación de expertos en los principales aspectos de la epilepsia que da como resultado una visión multidisciplinaria del tema y una síntesis del desarrollo reciente del conocimiento del fenómeno epiléptico y de los efectos clínicos fundamentales con especial énfasis en su clasificación actual. Aborda temas como Aspectos generales y clasificación de la epilepsia, Mecanismos de acción de fármacos antiepilépticos, Toxicología de los fármacos antiepilépticos, Síndromes epilépticos en edad pediátrica, Tratamiento médico de la epilepsia, Tratamiento quirúrgico de la epilepsia, Bases genéticas de la epilepsia, Aspectos sociales de la epilepsia, Aspectos legales de la epilepsia, entre otros. Se complementa con gráficas e imágenes referentes al tema

Cefalea y migraña / Headache and migraine

Documento elaborado con el fin de brindar mayor información de caracter científico a los médicos que laboran en el primer nivel de atención. En la presente guía de prescripción terapéutica, se presentan datos, clasificación y criterios diagnósticos para la cefalea, las neuralgias craneales y el dolor facial

Epilepsia / Epilepsy

Con el propósito de ayudar a la actualización de los médicos que prestan sus servicios en el primer nivel de atención, se presenta una Guía de prescripción terapéutica, misma que colaborará con mayor información científica de alto nivel y con ello, mejorará la calidad de la atención de la salud. Dicho documento se refiere al diagnóstico, cuidados, tratamiento y consideraciones especiales de la epilepsia

Granuloma en parenquima cerebral.Un modelo humano para el estudio de epilepsia / Granuloma in cerebral parenquima. A human model the study of epilepsy

Una secuela frecuente secundaria a cisticercosis en el parénquima cerebral es el granuloma calcificado. En la mayoría de los pacientes, la única manifestación clínica es epilepsia, frecuentemente en forma de crisis parciales. El granuloma parenquimatoso cerebral es una pequeña lesión no progresiva y bien definida fácilmente detectable por tomografía computarizada. En este estudio seleccionamos 149 pacientes con granuloma cerebral único y crisis epilépticas parciales. Aunque en general la manifestación de epilepsia se encontró de acuerdo a la tomografía de la lesión cerebral, algunos hallazgos en pacientes no están de acuerdo con conceptos clásicos de localización cerebral en epilepsia y apoyan datos recientes que demuestran amplias variaciones individuales. En base a nuestras observaciones, proponemos el estudio de pacientes con epilepsia secundaria a un granuloma parenquimatoso, secuela de cisticerco como un modelo para análisis de los mecanismos fisiopatológicos de la epilepsia.