[Linkage analysis of the 15q25-15q22 region in an extended multigenerational family segregating for idiopathic epilepsy]. / Análisis de ligamiento a la región 15Q25-15Q22 de una familia multigeneracional extendida segregando epilepsia idiopática.

INTRODUCTION: Linkage analyses provide strong evidence of how genetic factors influence epilepsy, due to the fact that they involve the determination of the cosegregation of specific marker alleles with epilepsy within families. AIMS: Our aim was to determine whether there was some kind of propensity to develop generalised idiopathic epilepsy (GIE) in the 15q22.1-q25.1 region in an extended multigenerational family from the Paisa de Antioquia community, which is a genetic isolate located in Colombia that segregates for GIE and has a strong capacity to detect linkage. PATIENTS AND METHODS: We selected a family containing a number of individuals suffering from epilepsy who visited the Antioquia Neurological Institute. Each affected individual had to have been diagnosed by a neurologist as suffering from non-myoclonic idiopathic epilepsy or from partial idiopathic epilepsy. All patients suspected of suffering from idiopathic epilepsy were submitted to video monitoring in order to characterise seizures electroencephalographically. RESULTS: Of the 106 individuals in this family who were included in the family tree, 76 were genotyped; 15 of them suffered from generalised clonic tonic seizures and six were considered as being possibly affected. Lod score results were significantly negative for all the markers in relation to each of the models under consideration. CONCLUSIONS: The possibility of the genes that code for the a-3, a-5 and b-4 subunits of the neuronal nicotinic acetylcholine receptor (CHRNA3, CHRNA5 and CHRNB4) situated in the 15q region being responsible for the familial aggregation of GIE in this family, as has been suggested in previous studies in other families, was ruled out.

[Linkage analysis in an extended multigenerational family segregating for idiopathic epilepsy]. / Análisis de ligamiento en una familia multigeneracional extendida que segrega para epilepsia idiopática.

INTRODUCTION: Linkage analyses enable us to identify the loci that bestow susceptibility to certain diseases which are assumed to have a genetic aetiology by determining the cosegregation of alleles of specific markers within families. AIMS: The aim of this study was to determine whether there is generalised idiopathic epilepsy (GIE) susceptibility in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions within an extended multigenerational family belonging to the Paisa community in Antioquia, a genetic isolate located in Colombia segregating for GIE with a strong capacity for detecting linkage. PATIENTS AND METHODS: A family with a number of individuals affected by idiopathic epilepsy who visited the Instituto Neurológico de Antioquia was selected for study. An affected individual was required to have been diagnosed by a neurologist as suffering from non-myoclonic idiopathic epilepsy or partial idiopathic epilepsy. All patients suspected of suffering from idiopathic epilepsy were submitted to video monitoring in order to characterise the seizures electroencephalographically. RESULTS: Of the 106 individuals in this family that were included in the family tree, 76 were genotyped, 15 of whom were affected by generalised clonic tonic seizures and six were considered to be possibly affected. Results of the lod score were significantly negative for all the markers in relation to each model that was considered. CONCLUSIONS: The possibility of the genes located in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions being responsible for the familial aggregation of GIE in this family was ruled out, which is in accordance with claims made in previous studies conducted on other families.

[Risk factors for seizure recurrence and short term outcome after epilepsy surgery for mesial temporal sclerosis]. / Factores de riesgo para recurrencia de convulsiones y pronóstico a corto plazo en cirugía de epilepsia para esclerosis mesial temporal.

AIM: To establish risk factors for seizure recurrence and short term Engel classification after surgery for mesial temporal sclerosis (MTS). PATIENTS AND METHODS: Nested case-control study in a cohort of patients diagnosed with MTS by magnetic resonance imaging and who had at least two years of postsurgical follow-up; patients with bilateral MTS were excluded. Clinical characteristics, epileptogenic focus in video-electroencefalography (video-EEG) and surgical issues were evaluated regarding to seizure recurrence during the first two postsurgical years and Engel classification in the first and second anniversary after surgery. RESULTS: From October 2001 to June 2008, 144 patients with MTS were evaluated as candidates for epilepsy surgery; until June 2007, 89 patients underwent epilepsy surgery, 51.7% with left MTS. 35.8% of patients experienced seizure recurrence before two post-surgical years; presurgical risk factor associated to this recurrence was bitemporal focus or single temporal focus with contralateral dissemination by video-EEG (odds ratio = 6.32; 95% confidence interval = 1.64-26.41); and post-surgical, seizures that occurred in the first month of surgery (p = 0004). No association with seizure recurrence was found with gender, presurgical tonic-clonic seizures, MTS side and epilepsy duration. 66.3% and 75.8% of patients were Engel I classified in the first and second anniversary after surgery, respectively. 91% of operated patients showed a good outcome after two years of epilepsy surgery. CONCLUSION: Epileptogenic focus location by electrophysiology is a fundamental factor in short term outcome after surgery for MTS.

Factores de riesgo para recurrencia de convulsiones y pronóstico a corto plazo en cirugía de epilepsia para esclerosis mesial temporal / Risk factors for seizure recurrence and short term outcome after epilepsy surgery for mesial temporal sclerosis

Objetivo. Determinar los factores de riesgo para recurrencia de convulsiones y la clasificación posquirúrgica a corto plazo en pacientes operados por esclerosis mesial temporal (EMT). Sujetos y métodos. Estudio de casos y controles anidado en la cohorte de pacientes con EMT diagnosticados por resonancia magnética con dos años de seguimiento posquirúrgico; se excluyeron pacientes con EMT bilateral. Se evaluaron características clínicas prequirúrgicas, foco epileptogénico en videoelectroencefalograma (video-EEG) y variables quirúrgicas con respecto a recurrencia de convulsiones en los primeros dos años tras la intervención y clasificación de Engel en el primer y segundo aniversario de la cirugía. Resultados. Entre octubre de 2001 y junio de 2008 se evaluó a 144 pacientes con EMT candidatos a cirugía de epilepsia; hasta junio de 2007, se había operado a 89 pacientes, un 51,7% con EMT izquierda. El 35,8% de los pacientes presentó recurrencia de convulsiones antes del segundo año tras la intervención; el factor de riesgo prequirúrgico asociado a recurrencia fue foco bitemporal o temporal único con diseminación contralateral por video-EEG (odds ratio = 6,32; intervalo de confianza al 95% = 1,64- 26,41); y el posquirúrgico, la presencia de convulsiones durante el primer mes tras la operación (p = 0,0004); no se encontró asociación con recurrencia para género, convulsiones tonicoclónicas generalizadas prequirúrgicas, lado de la EMT ni tiempo de evolución prequirúrgica de la epilepsia. El 66,3 y el 75,8% de los pacientes estaban en Engel I al primer y segundo año de la cirugía, respectivamente. El 91% de los pacientes intervenidos estaba en buen pronóstico posquirúrgico a los dos años. onclusión. La localización del foco epileptogénico por electrofisiología es un factor determinante en el pronóstico posquirúrgico a corto plazo en la EMT (AU)

Aim. To establish risk factors for seizure recurrence and short term Engel classification after surgery for mesial temporal sclerosis (MTS). Patients and methods. Nested case-control study in a cohort of patients diagnosed with MTS by magnetic resonance imaging and who had at least two years of postsurgical follow-up; patients with bilateral MTS were excluded. Clinical characteristics, epileptogenic focus in video-electroencefalography (video-EEG) and surgical issues were evaluated regarding to seizure recurrence during the first two postsurgical years and Engel classification in the first and second anniversary after surgery. Results. From October 2001 to June 2008, 144 patients with MTS were evaluated as candidates for epilepsy surgery; until June 2007, 89 patients underwent epilepsy surgery, 51.7% with left MTS. 35.8% of patients experienced seizure recurrence before two post-surgical years; presurgical risk factor associated to this recurrence was bitemporal focus or single temporal focus with contralateral dissemination by video-EEG (odds ratio = 6.32; 95% confidence interval = 1.64-26.41); and post-surgical, seizures that occurred in the first month of surgery (p = 0004). No association with seizure recurrence was found with gender, presurgical tonic-clonic seizures, MTS side and epilepsy duration. 66.3% and 75.8% of patients were Engel I classified in the first and second anniversary after surgery, respectively. 91% of operated patients showed a good outcome after two years of epilepsy surgery. Conclusion. Epileptogenic focus location by electrophysiology is a fundamental factor in short term outcome after surgery for MTS (AU)

Análisis de ligamiento en una familia multigeneracional extendida que segrega para epilepsia idiopática / Linkage analysis in an extended multigenerational family segregating for idiopathic epilepsy

Introducción. Los análisis de ligamiento permiten identificar loci que confieren susceptibilidad a diversas enfermedades de las que se presume una etiología genética, mediante la determinación de la cosegregación de alelos de marcadores específicos dentro de las familias. Objetivo. Determinar si existe susceptibilidad para desarrollar epilepsia idiopática generalizada (EIG) en las regiones 8q22.1 -q24.23, 16p13.3 y 21q22.3 en una familia multigeneracional extendida perteneciente a la comunidad Paisa de Antioquia, una población aislada genéticamente localizada en Colombia que segrega para EIG y con una gran potencialidad para detectar ligamiento. Pacientes y métodos. Se selecciona una familia con múltiples individuos afectados de epilepsia idiopática que consultaron al Instituto Neurológico de Antioquia. El individuo afectado debía tener un diagnóstico realizado por un neurólogo de epilepsia idiopática no mioclónica o de epilepsia idiopática parcial. Se realizó una videomonitorización a todos los pacientes con sospecha de epilepsia idiopática, con el fin de caracterizar electroencefalográficamente las crisis. Resultados. De los 106 individuos en esta familia incluidos en la genealogía, se genotipificaron 76, de los que 15 estaban afectados de crisis tonicoclónicas generalizadas y seis se consideraron posiblemente afectados. Los resultados de lod score son significativamente negativos para todos los marcadores con relación a cada modelo considerado. Conclusiones. Se descarta que los genes localizados en las regiones 8q22.1 -q24.23, 16p13.3 y 21q22.3 sean los responsables de la agregación familiar de la EIG en esta familia, como lo han sugerido estudios anteriores en otras familias (AU)

Introduction. Linkage analyses enable us to identify the loci that bestow susceptibility to certain diseases which are assumed to have a genetic aetiology by determining the cosegregation of alleles of specific markers within families. Aims. The aim of this study was to determine whether there is generalised idiopathic epilepsy (GIE) susceptibility in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions within an extended multigenerational family belonging to the Paisa community in Antioquia, a genetic isolate located in Colombia segregating for GIE with a strong capacity for detecting linkage. Patients and methods. A family with a number of individuals affected by idiopathic epilepsy who visited the Instituto Neurológico de Antioquia was selected for study. An affected individual was required to have been diagnosed by a neurologist as suffering from nonmyoclonic idiopathic epilepsy or partial idiopathic epilepsy. All patients suspected of suffering from idiopathic epilepsy were submitted to video monitoring in order to characterise the seizures electroencephalographically. Results. Of the 106 individuals in this family that were included in the family tree, 76 were genotyped, 15 of whom were affected by generalised clonic tonic seizures and six were considered to be possibly affected. Results of the lod score were significantly negative for all the markers in relation to each model that was considered. Conclusions. The possibility of the genes located in the 8q22.1 -q24.23, 16p13.3 and 21q22.3 regions being responsible for the familial aggregation of GIE in this family was ruled out, which is in accordance with claims made in previous studies conducted on other families (AU)