[Functional connectivity derived from an electroencephalogram during non-REM sleep in autism spectrum disorders]. / Conectividad funcional derivada del electroencefalograma durante el sueño no REM en los trastornos del espectro autista.

AIM: To know the differences in the patterns of functional connectivity, the topological characteristics of the network and the relationship between these latter and the interictal epileptiform anomalies in children with primary and secondary autism spectrum disorder (ASD). PATIENTS AND METHODS: A retrospective study was conducted with 27 children aged between 3 and 13 years diagnosed with ASD. Subjects were submitted to an electroencephalogram in a functional state of spontaneous sleep. Functional connectivity and the properties of the network were analysed using data obtained from the electroencephalogram during the N2 stage of non-REM sleep. The frequency of discharge of the interictal epileptiform activity (FDIEA) was determined and was correlated with the topological properties of the network. RESULTS: Synchronisation was diminished in patients with secondary ASD for the alpha frequency and increased for the theta and delta frequency compared with patients with primary ASD. Local alpha efficiency was higher in patients who presented interictal epileptiform activity. Additionally, in patients with secondary ASD there was a statistically significant positive and negative correlation between FDIEA and the topological properties of the network. CONCLUSIONS: Patients with secondary ASD display patterns of functional connectivity that are weaker for the alpha frequency and stronger for theta and delta than patients with primary ASD. In patients with secondary ASD, the interictal epileptiform activity is related to local and global connectivity of the network for the alpha and beta bands during non-REM sleep.

TITLE: Conectividad funcional derivada del electroencefalograma durante el sueño no REM en los trastornos del espectro autista.Objetivo. Conocer las diferencias en los patrones de conectividad funcional, las caracteristicas topologicas de la red y la relacion de estas con las anomalias epileptiformes interictales en niños con trastorno del espectro autista (TEA) primario y secundario. Pacientes y metodos. Se realizo un estudio retrospectivo con 27 niños de 3-13 años diagnosticados con TEA, a los que se les realizo un electroencefalograma en estado funcional de sueño espontaneo. Se analizo la conectividad funcional y las propiedades de la red a partir de los datos obtenidos del electroencefalograma durante la etapa N2 del sueño no REM. Se determino la frecuencia de descarga de la actividad epileptiforme interictal (FDAEI) y se correlaciono con las propiedades topologicas de la red. Resultados. Los pacientes con TEA secundario tenian una disminucion de la sincronizacion para la frecuencia alfa y un incremento para la frecuencia theta y delta en comparacion con los pacientes con TEA primario. La eficiencia local alfa fue mayor en los pacientes que presentaban actividad epileptiforme interictal. Ademas, en los pacientes con TEA secundario, existia una correlacion positiva y negativa estadisticamente significativa entre la FDAEI y las propiedades topologicas de red. Conclusiones. Los pacientes con TEA secundario muestran patrones de conectividad funcional mas debiles para la frecuencia alfa y mas fuerte para la theta y delta que los pacientes con TEA primario. En pacientes con TEA secundario, la actividad epileptiforme interictal se relaciona con la conectividad local y global de la red para las bandas de frecuencia alfa y beta durante el sueño no REM.

Corpora amylacea in the neocortex in patients with temporal lobe epilepsy and focal cortical dysplasia.

INTRODUCTION: Corpora amylacea (CoA) are present in about 60% of atrophic hippocampi resected from patients with drug resistant temporal lobe epilepsy (DRTLE). They have also been described in the lateral temporal neocortex, although less frequently. OBJECTIVE: The objective is to measure the presence, distribution and density of CoA in the lateral temporal lobes of patients with DRTLE and focal cortical dysplasia (FCD), also examining how CoA density may be linked to demographic and clinical traits. METHODS: Resected tissue from 35 patients was analysed. CoA density was assessed with a semi-quantitative scale according to the criteria established by Cherian et al. RESULTS: Presence of CoA in the neocortex of 9 patients was associated with hippocampal sclerosis (FCD type iiia, 7 cases), disembryoplastic neuroepithelial tumour (FCD type iiib, 1 case), and cavernous angioma (FCD type iiic, 1 case). The meningeal surface (MS) was involved in all cases, and 8 cases displayed CoA in the cerebral parenchyma (white matter) and around blood vessels. CoA density on the MS showed a negative correlation with age at seizure onset (r = -0.828, P<.05) and a positive correlation with disease duration (r = 0.678, P<.05) but not with postoperative clinical outcome. CONCLUSIONS: Patients with DRTLE and a primary lesion (hippocampal sclerosis, tumour, vascular malformation) associated with mild FCD were shown to have CoA deposits in the neocortex. No association was found between presence of CoA and clinical outcome one year after surgery.

Relación entre los resultados del Electroencefalograma digital y la evaluación clínica, neuropsicológica e imagenológica en pacientes con diagnóstico clínico de Parálisis Cerebral / Relation between digital Electroencephalogram clinic results, neuropsychological and imagenologic evaluation in patients with cerebral palsy clinic diagnostic

Objetivo: Evaluar la relación existente entre los resultados del Electroencefalograma (EEG) digital y las anomalías clínicas, neuropsicológicas e imagenológicas detectadas en pacientes con el diagnóstico clínico de Parálisis Cerebral (PC). Sujetos y Métodos: Se realizó un estudio descriptivo longitudinal retrospectivo de los informes de EEG emitidos por un especialista en Neurofisiología clínica en 64 pacientes con el diagnóstico clínico de PC. Los datos fueron registrados desde enero del año 2000 hasta diciembre del año 2005 en el Laboratorio de Neurofisiología Clínica del CIREN. Incluimos a pacientes con edades entre 2 y 15 años, con diagnóstico revisado de la historia clínica de PC. Se tabularon las variables evaluadas en los registros de EEG, y se relacionaron con variables clínicas, neuropsicológicas e imagenológicas. Todos los registros se realizaron en un Equipo MEDICID 4 Neuronic SA de producción cubana con el software Track Walker 2. Resultados: Se obtuvo que el 79 % del los registros electroencefalográficos fueron patológicos. Predominó la actividad epileptiforme en un 58%. El tipo de PC en nuestra casuística fue la espástica para un 50%. La causa de la PC fue perinatal en un 43%. Las enfermedades asociadas fueron Retardo del desarrollo psicomotor (RDP), Retraso mental (RM) y epilepsia. Se evidenció una asociación estadísticamente significativa entre la presencia de actividad epileptiforme y la epilepsia, entre los resultados del EEG y la presencia de lesión bilateral, así como entre la actividad epileptiforme y la presencia de RM, RDP y epilepsia. Conclusiones: Se constata una asociación estadísticamente significativa entre las anomalías epileptiformes y el diagnóstico clínico de epilepsia en pacientes con PC. Las anomalías del EEG se asocian mayormente con la extensión bilateral de la afectación motora, y con las lesiones detectadas mediante los estudios de Resonancia Magnética Nuclear (RMN). Existe una tendencia a la asociación entre las alteraciones Electroencefalográficas, el tipo de PC y la presencia de retardo en el desarrollo psicomotor y retraso mental. El EEG es un medio diagnóstico útil en la evaluación funcional de los pacientes con PC (AU)

Objetive: To evaluate the relation between digital Electroencephalogram (EEG) results and clinic, neuropsychological and imagenologic anomaly detected in patients with Cerebral Palsy (CP) diagnosis. Subject and method: Descriptive longitudinal retrospective study was made of EEG informs emitted by a clinical neurophysiologic specialist in 64 patients with CP diagnosis. The information was recorded from January 2000 to December 2005 in a Clinical Neurophysiologist laboratory of the International Center of Neurological Restoration. It included patients between 2 and 15 years old, with CP diagnostic checked in clinical history. The variables assessed were tabulated in EEG records and were associated to clinical, neuropsychology and imagenologic variables. All recordings were performed with the MEDICID 4 Neuronic SA equipment made in Cuba with Track Walker 2 software. Results: 79 % of the electroencephalographic records were pathological. In 58% of the cases there was a predominance of epileptiform activity. 50% suffered from spastic CP. The cause of CP was perinatal in 43%. The other associated conditions were Phychomotor Retardation (PR), Mental Delay (MD) and epilepsy. There was a statistically significant association between the presence of epileptiform activity and epilepsy between the EEG records and bilateral lesion and between the epileptiform activity and the presence of MD, PR and epilepsy. Conclusions: Our results demonstrate the exististence of a statistically significant association between epileptiform anomaly and epilepsy clinical diagnosis. It was confirmed that EEG anomaly is associated with bilateral extension of motor affectation and lesions detected with Magnetic Resonance Image (MRI) studies. There was an association tendency between electroencephalographic alteration, CP type, PR and MD presence. EEG is a useful diagnostic way for the functional evaluation of CP patients (AU)

Estudio prospectivo, abierto, controlado y aleatorizado de clobazam frente a carbamacepina en pacientes con crisis frecuentes de epilepsia rolándica / A prospective, open, controlled and randomised study of clobazam versus carbamazepine in patients with frequent episodes of rolandic epilepsy

Resumen. Introducción. No existen estudios controlados, aleatorizados y con régimen de dosificación flexibles en niños con epilepsia rolándica, por lo que la terapia es aún empírica. Objetivo. Evaluar la eficacia y la tolerabilidad del clobazam (CLB) comparado con la carbamacepina (CBZ) en la epilepsia rolándica. Pacientes y métodos. Estudio prospectivo, abierto, controlado, aleatorizado de CBZ frente a CLB en niños con epilepsia rolándica con seguimiento durante dos años. Se aleatorizaron 45 pacientes y terminaron el estudio 38 sujetos. Se indicó un régimen de dosificación flexible. Se evaluó el control de crisis, el rendimiento escolar, el comportamiento, la adherencia al tratamiento, el grado de satisfacción de los padres y el perfil de efectos adversos. Resultados. Ambos medicamentos fueron igualmente eficaces para controlar las crisis (el 94,1% de pacientes con CLB y el 100% con CBZ estaban libres de crisis al finalizar el estudio; p = 0,26). El CLB logró controlar las crisis más tempranamente (33,3 ± 45 frente a 48,2 ± 72,3 días; p < 0,05) y tuvo menos efectos adversos que la CBZ (aparecieron efectos adversos en tres pacientes con CLB y ocho con CBZ; p = 0). En dos pacientes en régimen de CBZ, las crisis empeoraron y junto con ello aparecieron complicaciones cognitivoconductuales. Conclusiones. La CBZ es un medicamento eficaz en la epilepsia rolándica, pero puede asociarse a un empeoramiento de las crisis, así como a déficit cognitivos y conductuales. El CLB en monoterapia parece ser un fármaco eficaz y mejor tolerado en este tipo de epilepsia (AU)

Summary. Introduction. To date no controlled, randomised studies with flexible dose regimens have been conducted in children with rolandic epilepsy, and therapy is therefore still empirical. Aim. To evaluate the effectiveness and safety of clobazam (CLB) compared with that of carbamazepine (CBZ) in rolandic epilepsy. Patients and methods. A prospective, open, controlled and randomised study was carried out to compare CBZ and CLB in children with rolandic epilepsy with a follow-up over a twoyear period. A random sample of 45 patients was taken and 38 of them finished the study. A flexible dose regimen was indicated. Control of seizures, academic performance, behaviour, adherence to treatment, parents’ degree of satisfaction and side effect profiles were all evaluated. Results. Both drugs were equally effective at controlling seizures (94.1% of patients with CLB and 100% of those with CBZ were free of seizures on ending the study; p = 0.26). CLB controlled seizures earlier (33.3 ± 45 days versus 48.2 ± 72.3; p < 0.05) and had fewer side effects than CBZ (side effects appeared in three patients with CLB and in eight of those on CBZ; p = 0). In two of the patients taking CBZ, the seizures got worse and a series of cognitive-behavioural complications also appeared. Conclusions. CBZ is an effective drug in rolandic epilepsy, but it may be associated with exacerbation of seizures as well as with cognitive-behavioural impairment. CLB in monotherapy seems to be an effective and better tolerated drug in this kind of epilepsy (AU)

[A prospective, open, controlled and randomised study of clobazam versus carbamazepine in patients with frequent episodes of Rolandic epilepsy]. / Estudio prospectivo, abierto, controlado y aleatorizado de clobazam frente a carbamacepina en pacientes con crisis frecuentes de epilepsia rolándica.

INTRODUCTION: To date no controlled, randomised studies with flexible dose regimens have been conducted in children with rolandic epilepsy, and therapy is therefore still empirical. AIM: To evaluate the effectiveness and safety of clobazam (CLB) compared with that of carbamazepine (CBZ) in rolandic epilepsy. PATIENTS AND METHODS: A prospective, open, controlled and randomised study was carried out to compare CBZ and CLB in children with rolandic epilepsy with a follow-up over a two-year period. A random sample of 45 patients was taken and 38 of them finished the study. A flexible dose regimen was indicated. Control of seizures, academic performance, behaviour, adherence to treatment, parents' degree of satisfaction and side effect profiles were all evaluated. RESULTS: Both drugs were equally effective at controlling seizures (94.1% of patients with CLB and 100% of those with CBZ were free of seizures on ending the study; p = 0.26). CLB controlled seizures earlier (33.3 +/- 45 days versus 48.2 +/- 72.3; p < 0.05) and had fewer side effects than CBZ (side effects appeared in three patients with CLB and in eight of those on CBZ; p = 0). In two of the patients taking CBZ, the seizures got worse and a series of cognitive-behavioural complications also appeared. CONCLUSIONS: CBZ is an effective drug in rolandic epilepsy, but it may be associated with exacerbation of seizures as well as with cognitive-behavioural impairment. CLB in monotherapy seems to be an effective and better tolerated drug in this kind of epilepsy.

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: an electrocorticography study.

BACKGROUND: Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. SUBJECTS AND METHODS: A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. RESULTS: Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. CONCLUSIONS: Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.

Muerte neuronal en la neocorteza de pacientes con epilepsia del lóbulo temporal resistente a fármacos / Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients

Introducción. La participación de mecanismos de muerteapoptótica en la epilepsia del lóbulo temporal resistente afármacos (ELTRF) es un aspecto muy discutido en la actualidad.Investigamos si existe pérdida neuronal y la inmunodeteccióna diferentes marcadores de muerte en tejido neocorticalen ocho pacientes con ELTRF y como tejido controlse evaluaron cinco neocortezas de sujetos fallecidos porcausas no neurológicas, pareados en edad y sexo.Métodos. La evaluación de la pérdida neuronal se realizópor medio de un estudio estereológico y por técnica inmunohistoquímicacon el marcador sinaptofisina. Se evaluóla inmunopositividad a diferentes marcadores apoptóticos(anexina V, caspasa 3 y 8, bcl-2 y p53), así como la detecciónde fragmentación del ácido desoxirribonucleico (ADN) (TUNEL),y se realizó en todos los casos un doble marcaje con sinaptofisina.Los resultados fueron evaluados por microscopiaconfocal y analizados por el programa Zeiss LSM 5 ImageBrowser, 2.80.1113 (Alemania).Resultados. Se observó una disminución estadísticamentesignificativa del número total de células (p<0,05), asícomo de las células sinaptofisina+ (p<0,01) en la neocorteza(capa IV) de los pacientes con ELTRF al ser comparadoscon el tejido control. No mostraron diferencias significativaslos marcadores apoptóticos bcl-2, p53, caspasa 3 y 8 paraninguna de las capas de neocorteza, mientras que sí resultóestadísticamente aumentado el número de células TUNEL+(p<0,05) y anexina V+ (p<0,05) en la capa IV neocortical delos pacientes.Conclusiones. Este grupo de evidencias hablan a favorde la existencia en la capa IV de neocorteza de una afectaciónen el número neuronal que se puede asociar a un procesode muerte apoptótica por una vía no dependiente de caspasas,sin que pueda ser descartada la muerte por necrosis (AU)

Introduction. Participation of apoptotic death mechanisms in drug resistant temporal lobe epilepsy (DRTLE) is currently under great debate. We have investigated if there is neuronal loss and the immunodetection to differentmarkers in neocortical tissue death in eigth patients with DRTLE. The neocortexes of five patients deceased due to non-neurological causes, paired in age and gender were evaluated as control tissue. Methods. The evaluation of neuronal loss was made by means of a stereological study and with immunohisto chemical techniques with the synaptophysin marker. Immunopositivity to different apoptotic markers (annexin V, caspase 3 and 8, bcl-2 and p53) and detection of deoxyribonucleic acid (DNA) fragmentation (TUNEL) wereanalyzed and double labeling with synaptophysin was performed in every case. The results were evaluated with confocal microscope and analyzed with the Zeiss LSM 5 Image Browser Program, 2.80.1113 (Germany). Results. A statistically significant decrease in the total number of cells (p < 0.05) and the synaptophysin cells+ (p<0.01) in the neocortex (layer IV) of the patients with DRTLE when compared with the control tissue was found. No significant differences were found in the apoptotic markers bcl-2, p53, caspase 3 and 8 for any of the neocortex layers while there was a statistically significantincrease in the number of TUNEL cells+ (p<0.05) and annexin V+ (p<0.05) in the neocortical layer IV of the patients. Conclusions. This group of evidence speaks in favor of the existence of an effect on the neuronal number in the neocortex layer IV that may be associated with non caspase dependent apoptotic death process, without beingable to rule out death by necrosis

[Pathological neocortical findings in patients with medication-resistant medial temporal lobe epilepsy submitted to surgery]. / Hallazgos patológicos neocorticales en pacientes con epilepsia del lóbulo temporal medial farmacorresistente sometidos a cirugía.

INTRODUCTION: The dual pathology consisting of hippocampal sclerosis plus focal cortical dysplasia (FCD) is often reported in patients with medication-resistant medial temporal lobe epilepsy (MTLE). AIMS: To determine the histopathological changes that take place in the neocortex of patients with medication-resistant MTLE submitted to surgery and to evaluate the relation between the histopathological changes, pathological background and the clinical course of patients who had received surgical treatment. MATERIALS AND METHODS: Tissue obtained by en bloc resection from the neocortex of 18 patients with MTLE refractory to medical treatment was processed histologically and a tailored temporal lobectomy was performed with electrocorticography. RESULTS: Dual pathology was diagnosed in 13 patients (72.2%). Imaging studies confirmed the existence of mesial sclerosis of the temporal in 100% of cases and there was no evidence of neocortical lesions. Histologically, 46.15% and 38.46% of the patients were diagnosed as belonging to FCD type 1a and FCD type 1b, respectively. Only one patient presented FCD type 2a. A statistically significant relation was found between the presence of dual pathology and the existence of an early precipitating injury (p = 0.04). One year after surgery, 72.7% (8/11) patients with dual pathology were classified as belonging to Engel class I. CONCLUSIONS: In patients with MTLE there are microscopic FCD-type alterations in the neocortex. There is an association between these alterations and the existence of an initial precipitating injury. Complete resection of the epileptogenic area, which is guaranteed by the lobectomy tailored by electrocorticography, allows patients to enjoy a favourable post-surgical progression one year after surgery.

[Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients]. / Muerte neuronal en la neocorteza de pacientes con epilepsia del lóbulo temporal resistente a fármacos.

Introduction. Participation of apoptotic death mechanisms in drug resistant temporal lobe epilepsy (DRTLE) is currently under great debate. We have investigated if there is neuronal loss and the immunodetection to different markers in neocortical tissue death in eigth patients with DRTLE. The neocortexes of five patients deceased due to non-neurological causes, paired in age and gender were evaluated as control tissue. Methods. The evaluation of neuronal loss was made by means of a stereological study and with immunohistochemical techniques with the synaptophysin marker. Immunopositivity to different apoptotic markers (annexin V, caspase 3 and 8, bcl-2 and p53) and detection of deoxyribonucleic acid (DNA) fragmentation (TUNEL) were analyzed and double labeling with synaptophysin was performed in every case. The results were evaluated with confocal microscope and analyzed with the Zeiss LSM 5 Image Browser Program, 2.80.1113 (Germany). Results. A statistically significant decrease in the total number of cells (p < 0.05) and the synaptophysin cells+ (p<0.01) in the neocortex (layer IV) of the patients with DRTLE when compared with the control tissue was found. No significant differences were found in the apoptotic markers bcl-2, p53, caspase 3 and 8 for any of the neocortex layers while there was a statistically significant increase in the number of TUNEL cells+ (p<0.05) and annexin V+ (p<0.05) in the neocortical layer IV of the patients. Conclusions. This group of evidence speaks in favor of the existence of an effect on the neuronal number in the neocortex layer IV that may be associated with noncaspase dependent apoptotic death process, without being able to rule out death by necrosis. Key words: Drug resistant temporal lobe epilepsy. Apoptosis. Necrosis. Neuronal loss. Neurología 2008;23(9):555-565.

[Volumetric measurement and digital electroencephalography in patients with medication-resistant medial temporal lobe epilepsy submitted to surgery]. / Volumetria y electroencefalografía digital en pacientes con epilepsia del lobulo temporal medial farmacorresistente sometidos a cirugía.

AIM: To assess the value of volumetric measurement by means of magnetic resonance imaging (MRI) and interictal electroencephalogram (EEG) in pre- and post-operative assessment of patients with medication-resistant medial temporal lobe epilepsy (MTLE) who were submitted to surgery. PATIENTS AND METHODS: We evaluated 12 volumetric studies carried out using MRI and 24 digital EEG records for six patients suffering from complex partial seizures that were resistant to medical treatment and had their origin in the temporal lobe. A volumetric analysis was performed using MRI to study the epileptogenic region and the frequencies at which interictal epileptiform discharges (IED/minute) appeared before, at six months and at one year after surgery were calculated; a correlation was observed between the volumetric analysis and the irritative and epileptogenic region. RESULTS: The volumes of both the ipso and contralateral hippocampuses were smaller in comparison to the increased frequency of the IED in the mesial regions. The inferior temporal lobes and the parahippocampal cortex have reduced volumes ipsolateral to the epileptogenic region. At six months after performing the temporal lobectomy, the IED frequency decreased with respect to the pre-operative IED. A negative correlation was found between the resected volume of the parahippocampal cortex and the inferior temporal lobe, and the post-operative IED frequency at one year. CONCLUSIONS: In patients with medication resistant MTLE the volumes of other structures in the medial temporal lobe are diminished, in addition to the hippocampus, and they are seen to have a smaller volume on the side that is ipsolateral to the epileptogenic region. There is a relation between the volume of the resected hippocampus and the post-operative IED frequency in patients with MTLE who successfully underwent a temporal lobectomy. Volumetric analysis of the epileptogenic lesion using MRI provides localising information that is valuable in the pre-operative assessment of patients with medication resistant MTLE who are submitted to surgery.

Hallazgos patológicos neocorticales en pacientes con epilepsia del lóbulo temporal medial farmacorresistente sometidos a cirugía / Pathological neocortical findings in patients with medication-resistant medial temporal lobe epilepsy submitted to surgery

La patología dual compuesta por esclerosis hipocampal y displasia cortical focal (DCF) se describecon frecuencia en pacientes con epilepsia del lóbulo temporal medial (ELTM) farmacorresistente. Objetivos. Determinar los cambios histopatológicos en la neocorteza de pacientes con ELTM farmacorresistente sometidos a cirugía y evaluar la relación entre los cambios histopatológicos, los antecedentes patológicos y la evolución clínica en los pacientes operados. Materialesy métodos. Se procesó histológicamente el tejido resecado en bloque (neocorteza) de 18 pacientes con ELTM refractaria a tratamiento médico, y se les realizó lobectomía temporal ajustada por electrocorticografía. Resultados. Se diagnóstico patología dual en 13 pacientes (72,2%). Los estudios imagenológicos confirmaron en el 100% de los casos la esclerosis mesialdel temporal y no existieron evidencias de lesión neocortical. Histológicamente, el 46,15% y el 38,46% de los pacientes fueron diagnosticados como DCF tipo 1a y DCF tipo 1b, respectivamente. Sólo un paciente presentó DCF tipo 2a. Se demostró una relación estadísticamente significativa entre la presencia de patología dual y la existencia de una daño precipitante inicial (p = 0,04). El 72,7% (8/11) de los pacientes con patología dual un año después de la cirugía se clasificó en la clase Ide Engel. Conclusiones. En los pacientes con ELTM existen alteraciones microscópicas en la neocorteza del tipo DCF. Estas alteraciones se asocian a la existencia de un daño precipitante inicial. La resección completa de la zona epileptogénica, garantizadapor la lobectomía ajustada por electrocorticografía, permite una buena evolución posquirúrgica un año después de la cirugía

The dual pathology consisting of hippocampal sclerosis plus focal cortical dysplasia (FCD) is oftenreported in patients with medication-resistant medial temporal lobe epilepsy (MTLE). Aims. To determine the histopathological changes that take place in the neocortex of patients with medication-resistant MTLE submitted to surgery and to evaluate the relation between the histopathological changes, pathological background and the clinical course of patients whohad received surgical treatment. Materials and methods. Tissue obtained by en bloc resection from the neocortex of 18 patients with MTLE refractory to medical treatment was processed histologically and a tailored temporal lobectomy was performed with electrocorticography. Results. Dual pathology was diagnosed in 13 patients (72.2%). Imaging studies confirmed the existenceof mesial sclerosis of the temporal in 100% of cases and there was no evidence of neocortical lesions. Histologically, 46.15% and 38.46% of the patients were diagnosed as belonging to FCD type 1a and FCD type 1b, respectively. Only one patient presented FCD type 2a. A statistically significant relation was found between the presence of dual pathology and the existenceof an early precipitating injury (p = 0.04). One year after surgery, 72.7% (8/11) patients with dual pathology were classified as belonging to Engel class I. Conclusions. In patients with MTLE there are microscopic FCD-type alterations in the neocortex.There is an association between these alterations and the existence of an initial precipitating injury. Complete resection of the epileptogenic area, which is guaranteed by the lobectomy tailored by electrocorticography, allows patients to enjoy a favourable post-surgical progression one year after surgery

Volumetría y electroencefalografía digital en pacientes con epilepsia del lóbulo temporal medial farmacorresistente sometidos a cirugía / Volumetric measurement and digital electroencephalography in patients with medications-resistant medial temporal lobe epilepsy submitted to surgery

Evaluar la contribución de la volumetría mediante resonancia magnética (RM) y el electroencefalograma(EEG) interictal en la evaluación pre y posquirúrgica de pacientes con epilepsia del lóbulo temporal medial (ELTM) farmacorresistente sometidos a cirugía. Pacientes y métodos. Se evaluaron 12 estudios volumétricos por RM y 24 registros de EEG digital correspondientes a seis pacientes con crisis parciales complejas refractarias a tratamiento médico de origen temporal.Se realizó el análisis volumétrico por RM, para el estudio de la zona epileptogénica, y se calculó la frecuencia de aparición de descargas epileptiformes interictales (DEI/minuto) antes, a los seis meses y al año de la cirugía, y se correlacionóel análisis volumétrico con la zona irritativa y epileptogénica. Resultados. Los volúmenes de los hipocampos tanto ipsi comocontralaterales están disminuidos de tamaño en comparación con el aumento de la frecuencia DEI en las zonas mesiales. Los lóbulos temporales inferiores y la corteza parahipocámpica se encontraron disminuidos de volumen ipsilaterales a la zona epileptogénica. La frecuencia de DEI disminuye a los seis meses de realizada la lobectomía temporal respecto a las DEI prequirúrgica.Se encontró correlación negativa entre el volumen resecado de la corteza parahipocámpica y el lóbulo temporal inferior con la frecuencia DEI posquirúrgica al año. Conclusiones. En pacientes con ELTM farmacorresistente se encuentrandisminuidos los volúmenes de otras estructuras del lóbulo temporal medial, además del hipocampo, y se constata un menor volumen de éstas, en el lado ipsilateral a la zona epileptogénica. El volumen de hipocampo resecado se relaciona con la frecuenciade DEI posquirúrgica de los pacientes con ELTM sometidos a lobectomía temporal exitosa. El análisis volumétricomediante RM de la lesión epileptogénica aporta información localizadora de utilidad en la evaluación prequirúrgica de pacientes con ELTM farmacorresistente sometidos a cirugía

To assess the value of volumetric measurement by means of magnetic resonance imaging (MRI) and interictalelectroencephalogram (EEG) in pre- and post-operative assessment of patients with medication-resistant medial temporal lobe epilepsy (MTLE) who were submitted to surgery. Patients and methods. We evaluated 12 volumetric studies carried out using MRI and 24 digital EEG records for six patients suffering from complex partial seizures that were resistant to medicaltreatment and had their origin in the temporal lobe. A volumetric analysis was performed using MRI to study the epileptogenic region and the frequencies at which interictal epileptiform discharges (IED/minute) appeared before, at six months and at oneyear after surgery were calculated; a correlation was observed between the volumetric analysis and the irritative and epileptogenic region. Results. The volumes of both the ipso and contralateral hippocampuses were smaller in comparison tothe increased frequency of the IED in the mesial regions. The inferior temporal lobes and the parahippocampal cortex havereduced volumes ipsolateral to the epileptogenic region. At six months after performing the temporal lobectomy, the IED frequency decreased with respect to the pre-operative IED. A negative correlation was found between the resected volume of the parahippocampal cortex and the inferior temporal lobe, and the post-operative IED frequency at one year. Conclusions. Inpatients with medication resistant MTLE the volumes of other structures in the medial temporal lobe are diminished, in addition to the hippocampus, and they are seen to have a smaller volume on the side that is ipsolateral to the epileptogenic region. There is a relation between the volume of the resected hippocampus and the post-operative IED frequency in patientswith MTLE who successfully underwent a temporal lobectomy. Volumetric analysis of the epileptogenic lesion using MRI provides localising information that is valuable in the pre-operative assessment of patients with medication resistant MTLE who are submitted to surgery

[Video-EEG evaluation complemented by spectral and EEG source analysis in patients with medication-resistant medial temporal lobe epilepsy]. / Evaluación videoelectroencefalográfica complementada con análisis espectral y de las fuentes generadoras del electroencefalograma en pacientes con epilepsia del lóbulo temporal medial resistente a los fármacos.

AIM: To evaluate the value of prolonged video-electroencephalographic (video-EEG) monitoring complemented with spectral and EEG source analysis in identifying the epileptogenic area in patients with medial temporal lobe epilepsy who are candidates for non-lesional resective surgery. PATIENTS AND METHODS: The electrographic patterns during the onset of seizures were evaluated in over 667 seizures from 41 patients with a clinical diagnosis of medication-resistant partial epilepsy. Analyses were performed using Harmonie software and variable resolution electrical tomography (VARETA). RESULTS: Video-EEG was used to determine that 53.6% of the patients evaluated suffered complex partial seizures of a temporal origin; these were characterised by having an average frequency of 5.56 +/- 1.56 Hz, while the non-temporal seizures displayed a frequency within the range 9.17 +/- 3.32 Hz. The topographic location of the dominant ictal frequency during the period of maximum spectral energy in patients with temporal lobe epilepsy enabled us to draw a distinction between a group of patients with mesial seizures and those with non-mesial seizures that exceeded the number that was determined by visual inspection of the EEG, that is, 78.9 versus 47.3%, respectively. There was a 100% coincidence between the area where the seizures began as defined by surface EEG complemented with spectral analysis, the generator of this activity as defined by VARETA and the epileptogenic region. CONCLUSIONS: The localising information provided by video-EEG complemented with spectral and EEG source analysis allows for non-invasive location of the epileptogenic region in patients with medial temporal lobe epilepsy even when structural imaging studies show an absence or bilaterality of abnormalities.

Evaluación videoelectroencefalográfica complementada con análisis espectral y de las fuentes generadoras del electroencefalograma en pacientes con epilepsia del lóbulo temporal medial resistente a los fármacos / Video-EEG evaluation complemented by spectral and EEG source analysis in patients with medication-resistant medal temporal lobe epilepsy

Objetivo. Evaluar la contribución de la monitorización prolongada videoelectroencefalográfica (video-EEG) complementada con análisis espectral y de las fuentes generadoras del electroencefalograma (EEG) en la identificación de la zona epileptogénica de pacientes con epilepsia del lóbulo temporal medial candidatos a cirugía resectiva no lesional. Pacientes y métodos. Se evaluaron los patrones electrográficos del inicio ictal en más de 667 crisis correspondientes a 41 pacientes con diagnóstico clínico de epilepsia parcial resistente a fármacos. Para el análisis se utilizaron el software Harmonie y la tomografía eléctrica de resolución variable (VARETA). Resultados. Mediante video-EEG se determinó que el 53,6% de los pacientes evaluados presentaba crisis parciales complejas de origen temporal; éstas se caracterizaron por una frecuencia media de 5,56 ± 1,56 Hz, mientras que las no temporales presentaron una frecuencia en el rango de 9,17 ± 3,32 Hz. La localización topográfica de la frecuencia ictal dominante durante el período de energía espectral máxima en los pacientes con epilepsia del lóbulo temporal permitió distinguir a un grupo de pacientes con crisis mesiales y otros no mesiales que superaron el número determinado por la inspección visual del EEG: un 78,9 frente a un 47,3%, respectivamente. Se evidenció una coincidencia del 100% entre la zona de inicio ictal definida por EEG de superficie complementada con análisis espectral, el generador de esta actividad definido por VARETA y la zona epileptogénica. Conclusiones. La información localizadora aportada por el video-EEG complementada con el análisis espectral y de las fuentes del EEG permite localizar de forma no invasiva la zona epileptogénica en pacientes con epilepsia del lóbulo temporal medial aun cuando los estudios imaginológicos estructurales evidencian ausencia o bilateralidad de anomalías

Aim. To evaluate the value of prolonged video-electroencephalographic (video-EEG) monitoring complemented with spectral and EEG source analysis in identifying the epileptogenic area in patients with medial temporal lobe epilepsy who are candidates for non-lesional resective surgery. Patients and methods. The electrographic patterns during the onset of seizures were evaluated in over 667 seizures from 41 patients with a clinical diagnosis of medication-resistant partial epilepsy. Analyses were performed using Harmonie software and variable resolution electrical tomography (VARETA). Results. Video- EEG was used to determine that 53.6% of the patients evaluated suffered complex partial seizures of a temporal origin; these were characterised by having an average frequency of 5.56 ± 1.56 Hz, while the non-temporal seizures displayed a frequency within the range 9.17 ± 3.32 Hz. The topographic location of the dominant ictal frequency during the period of maximum spectral energy in patients with temporal lobe epilepsy enabled us to draw a distinction between a group of patients with mesial seizures and those with non-mesial seizures that exceeded the number that was determined by visual inspection of the EEG, that is, 78.9 versus 47.3%, respectively. There was a 100% coincidence between the area where the seizures began as defined by surface EEG complemented with spectral analysis, the generator of this activity as defined by VARETA and the epileptogenic region. Conclusions. The localising information provided by video-EEG complemented with spectral and EEG source analysis allows for non-invasive location of the epileptogenic region in patients with medial temporal lobe epilepsy even when structural imaging studies show an absence or bilaterality of abnormalities

Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico. Réplica / Immunological disorders in epileptic patients linked to the localisation of the epileptogenic focus. Reply

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Réplica. Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico / Reply. Immunological disorders in epileptic patients are associated to the epileptogenic focus localization

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[Immunological disorders in epileptic patients are associated to the epileptogenic focus localization]. / Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico.

OBJECTIVE: Clinical and experimental data support the role of immune mechanisms in the pathogeny of epilepsy. The purpose of this work was to study the immunological aspects in 30 epileptic patients with complex partial crisis resistant to antiepileptic drugs. PATIENTS AND METHODS: The patients were evaluated by EEG-Video and they were grouped attending to epileptogenic focus localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n = 4). We also studied a group with psychogenic epilepsy (n = 4), this group was diagnosed after EEG-video evaluation. The following immunological evaluations has been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immunodiffusion test and lymphocytic subpopulations using immunocytochemical methods. We measured the percent of T and B lymphocytes (CD3 and CD20), helper/inductor lymphocyte T (CD4), suppressor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-DR). RESULTS: The results show a significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to different group of epileptogenic focus localization shown that the increase of CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The patients with extratemporal localization of focus and the psychogenic cases shown normal values for the evaluated immunological lymphocyte markers. We did not find a deficit in the humoral immunological aspects. CONCLUSIONS: Taking into account that patients diagnosed as psychogenic received an antiepileptic drug treatment identical to that of the other group, the observed immunological changes might be related with the patogeny of certain epilepsy variants associated with the focus localization and not with the medication.

Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico

Datos clínicos y experimentales evidencian el papel del sistema inmune en la patogenia de la epilepsia. El propósito de este trabajo es mostrar los resultados de los estudios inmunológicos realizados a 30 pacientes epilépticos con crisis parciales complejas refractarias a tratamiento médico, evaluados por vídeo-EEG. Pacientes y métodos. Los pacientes se agruparon de acuerdo con la localización del foco epileptogénico en: temporales (n = 16), lateralizados (n = 6) y extratemporales (n = 4). Se estudiaron, además, pacientes (n = 4) diagnosticados según la evaluación por vídeo-EEG como epilepsia psicógena. Se determinaron los niveles de inmunoglobulinas (IgG, IgM e IgA) por inmunodifusión radial y se cuantificaron por inmunocitoquímica los linfocitos T y B (CD3 y CD20), así como los marcadores linfocitarios: CD4, CD8, CD25 y HLA-DR. Resultados. Se evidenció un aumento significativo en el porcentaje de linfocitos T CD8+ (supresores/citotóxicos, p < 0,05) y de los marcadores de activación CD25 (células receptor IL-2) y HLA-DR (antígeno leucocitario humano DR). La evaluación de los parámetros inmunológicos en los diferentes grupos de localización del foco epileptogénico mostró que el aumento significativo de los linfocitos CD8+ se limita a los casos temporales y lateralizados (p < 0,01). Los pacientes con localización extratemporal y los casos psicógenos mostraron valores normales para todos los marcadores evaluados; este último grupo recibía el mismo tratamiento médico que el resto de los pacientes. Conclusiones. Estos resultados evidencian que existen alteraciones del sistema inmune en los pacientes epilépticos con crisis parciales complejas no asociadas al tratamiento antiepiléptico; las mismas pueden ser factores relevantes en la patogenia de la epilepsia y guardan relación con la localización del foco epileptogénico(AU)

Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico / Immunological disorders in epileptic patients are associated to the epileptogenic focus localization

Objetivo. Datos clínicos y experimentales evidencian el papel del sistema inmune en la patogenia de la epilepsia. El propósito de este trabajo es mostrar los resultados de los estudios inmunológicos realizados a 30 pacientes epilépticos con crisis parciales complejas refractarias a tratamiento médico, evaluados por vídeo-EEG. Pacientes y métodos. Los pacientes se agruparon de acuerdo con la localización del foco epileptogénico en: temporales (n = 16), lateralizados (n = 6) y extratemporales (n = 4). Se estudiaron, además, pacientes (n = 4) diagnosticados según la evaluación por vídeo-EEG como epilepsia psicógena. Se determinaron los niveles de inmunoglobulinas (IgG, IgM e IgA) por inmunodifusión radial y se cuantificaron por inmunocitoquímica los linfocitos T y B (CD3 y CD20), así como los marcadores linfocitarios: CD4, CD8, CD25 y HLA-DR. Resultados. Se evidenció un aumento significativo en el porcentaje de linfocitos T CD8+ (supresores/citotóxicos, p < 0,05) y de los marcadores de activación CD25 (células receptor IL-2) y HLA-DR (antígeno leucocitario humano DR). La evaluación de los parámetros inmunológicos en los diferentes grupos de localización del foco epileptogénico mostró que el aumento significativo de los linfocitos CD8+ se limita a los casos temporales y lateralizados (p < 0,01). Los pacientes con localización extratemporal y los casos psicógenos mostraron valores normales para todos los marcadores evaluados; este último grupo recibía el mismo tratamiento médico que el resto de los pacientes. Conclusiones. Estos resultados evidencian que existen alteraciones del sistema inmune en los pacientes epilépticos con crisis parciales complejas no asociadas al tratamiento antiepiléptico; las mismas pueden ser factores relevantes en la patogenia de la epilepsia y guardan relación con la localización del foco epileptogénico (AU)

Objective. Clinical and experimental data support the role of immune mechanisms in the pathogeny of epilepsy. The purpose of this work was to study the immunological aspects in 30 epileptic patients with complex partial crisis resistant to antiepileptic drugs. Patients and methods. The patients were evaluated by EEG-Video and they were grouped attending to epileptogenic focus localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n = 4). We also studied a group with psychogenic epilepsy (n = 4), this group was diagnosed after EEG-video evaluation. The following immunological evaluations has been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immunodiffusion test and lymphocytic subpopulations using immunocytochemical methods. We measured the percent of T and B lymphocytes (CD3 and CD20), helper/inductor lymphocyte T (CD4), suppresor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-DR). Results. The results show a significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to different group of epileptogenic focus localization shown that the increase of CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The patients with extratemporal localization of focus and the psychogenic cases shown normal values for the evaluated immunological lymphocyte markers. We did not find a deficit in the humoral immunological aspects. Conclusions. Taking into account that patients diagnosed as psyhcogenic received an antiepileptic drug treatment identical to that of the other group, the observed immunological changes might be related with the patogeny of certain epilepsy variants associated with the focus localization and not with the medication (AU)