Muerte súbita inesperada en epilepsia. Revisión sobre la implicación del tallo encefálico / Sudden unexpected death in epilepsy. Review about the brainstem involvement

RESUMEN La muerte súbita inesperada en epilepsia, se define como la muerte repentina -presenciada o no- de personas con epilepsia, no traumática ni por ahogamiento, con o sin evidencias de crisis, y en quienes el examen postmorten no revela una causa estructural o toxicológica de muerte. El objetivo de esta revisión es describir las evidencias más recientes, publicadas en la literatura, sobre la participación crucial del tallo encefálico en la fisiopatología de la muerte súbita inesperada en epilepsia. Se realizó una búsqueda bibliográfica en la base de datos computarizada PubMed. Los estudios en modelos animales han demostrado que los mecanismos de la muerte súbita inesperada en epilepsia involucran un primer evento mediado por una crisis, seguido por la despolarización cortical, que se propaga al tallo encefálico y que resulta en una disfunción autonómica causante de apnea central, edema pulmonar o arritmia cardiaca. Los estudios en humanos se han apoyado en las imágenes de resonancia magnética para evaluar el papel de diferentes áreas del tallo encefálico en la muerte súbita inesperada en epilepsia. Las evidencias acumuladas por la literatura, tanto en estudios con animales como humanos, evidencian el papel fundamental desempeñado por las estructuras del tallo encefálico en la fisiopatología de la muerte súbita inesperada en epilepsia.

ABSTRACT Sudden unexpected death in epilepsy is defined as the sudden death-whether witnessed or not-of people with epilepsy, not traumatic or due to drowning, with or without evidence of seizures, and in whom postmortem examination does not reveal a structural or toxicological cause of death. The aim of this review is to describe the most recent evidence published in the literature, on the crucial involvement of the brain stem in the pathophysiology of sudden unexpected death in epilepsy. A bibliographic search was conducted in PubMed computerized database. Studies in animal models have shown that the mechanisms of sudden unexpected death in epilepsy involve a first seizure-mediated event, followed by cortical depolarization, which spreads to the brainstem and results in autonomic dysfunction causing central apnea, pulmonary edema or cardiac arrhythmia. Studies in humans have relied on magnetic resonance imaging to assess the role of the brainstem in sudden unexpected death in epilepsy. The evidence accumulated in the literature, both in animal and in human studies, shows the role played by brainstem structures in the pathophysiology of sudden unexpected death in epilepsy.

Common Ictal and Interictal Perfusion Patterns: A Window into the Epileptogenic Network and SUDEP Mechanism in Drug-Resistant Focal Epilepsy.

BACKGROUND: Focal epilepsies have been described as a network disease. Noninvasive investigative techniques have been used to characterize epileptogenic networks. OBJECTIVE: This study aimed to describe ictal and interictal cortical and subcortical perfusion patterns using single- photon emission computed tomography (SPECT) in patients with drug-resistant epilepsy (DRE). METHODS: Thirty-five interictal-ictal SPECT scans were obtained from 15 patients with DRE. A methodology was developed to get a relative perfusion index (PI) of 74 cortical and sub-cortical brain structures. K-means algorithm, together with modified v-fold cross-validation, was used to identify the two regions of interest (ROIs) that represent hypoperfused and hyperperfused areas. RESULTS: In common with the individual analysis, the statistical analysis evidenced that the hyperperfusion ROIs resulting from group analysis during interictal and ictal involved mainly the cingulate gyrus, cuneus, lingual gyrus, and gyrus rectus as well as the putamen. ROIs hypoperfused included the red nucleus, the substantia nigra, and the medulla. The medians of the group analysis of the hypoperfusion and hyperperfusion ROIs were 0.601-0.565 and 1.133-1.119 for the ictal and interictal states, correspondingly. A group of mostly cortical structures involved in the hyperperfused ROIs in both interictal and ictal states showed no change or negative change in the transition from interictal to ictal state (mean change of -0.002). On the other hand, the brain stem, basal ganglia, red nucleus, and thalamus revealed a mean global change of 0.19, indicating a mild increase in the PI. However, some of these structures (red nucleus, substantia nigra, and medulla oblongata) remained hypoperfused during the interictal to ictal transition. CONCLUSION: The methodology employed made it possible to identify common cortical and subcortical perfusion patterns not directly linked to epileptogenicity, for a better epileptogenic network and sudden unexpected death (SUDEP) mechanism in DRE.

Potencial P300 durante una tarea de atención sostenida en pacientes conenfermedad de Parkinson / P300 event-related potential during sustained attention in Parkinson's disease patients

Objetivo: Evaluar la relación entre el potencial relacionado a eventos P300 con significado atencional visual y los resultados de la evaluación neuropsicológica en pacientes conenfermedad de Parkinson en estadios II y III de Hoehn y Yahr.Métodos: Se realizó un estudio analítico transversal donde se evaluaron 57 pacientes con enfermedad de Parkinson idiopática, atendidos entre diciembre de 2017 y abril de 2018, en el Centro Internacional de Restauración Neurológica, de La Habana. Se realizó el registro de P300, durante la ejecución de una tarea de atención sostenida visual. Se midió latencia y amplitud de la P300, lo que se correlacionó (test de correlaciones de Spearman, p< 0,01)con las variables demográficas, variables de eficiencia en la tarea de atención sostenida y variables neuropsicológicas. Se compararon los resultados de los grupos II y III de Hoehn y Yahr con respecto a todas las variables estudiadas (test de la U de Mann Whitney, p< 0,05).Resultados: Se constató una significativa diferencia de latencia entre grupos del componente P300 en el electrodo Pz. Fue más prolongado en el grupo III de Hoehn y Yahr.Se evidenciaron en el grupo II correlaciones negativas entre la latencia de P300 y el test de batería de evaluación frontal, y positivas entre la latencia de P300 y la prueba de Stroop.Las correlaciones entre el test de ba(AU)

Objective: To evaluate the relationship between the P300 event-related potential with visual attention significance and the results of neuropsychological evaluation in patientswith Parkinson's disease in Hoehn and Yahr stages II and III.Methods: A cross-sectional analytical study was carried out evaluating 57 patients with idiopathic Parkinson's disease, who were treated from December 2017 to April 2018 at theInternational Center for Neurological Restoration, in Havana. P300 was recorded during the execution of a visual sustained attention task. The latency and amplitude of P300 weremeasured, which was correlated (Spearman's correlation test, p <0.01) with demographic variables, efficiency variables in the sustained attention task and neuropsychological variables. The results of Hoehn and Yahr groups II and III were compared with respect to all the variables studied (Mann Whitney U test, p <0.05).Results: Significant latency difference was found between groups of P300 component in Pz electrode. It was more prolonged in Hoehn and Yahr group III. Negative correlations were found in group II between P300 latency and the frontal evaluation battery test, andpositive correlations between P300 latency and Stroop test. The correlations between the frontal evaluation battery test and P300 amplitude were positive, and between Stroop test and P300 amplitude were negative. Similar results were evident in group III regarding P300 amplitude, which corresponded to worse performance in the neuropsychological evaluation.Conclusions: A close relationship between P300 event-related potential with visual attention significance and the results of the neuropsychological evaluation in Parkinson's disease patients, in Hoehn and Yahr stages II and III, was verified. P300 potential was an objective examination that reinforced the validity of the neuropsychological evaluationresults(AU)

Consentimiento informado en pacientes con epilepsias intratables / Informed consent in patients with intractable epilepsy

La ética médica aborda, entre otros aspectos, la relación médico-paciente, de la cual se deriva el término consentimiento informado como su máxima expresión. La epilepsia afecta al 1-2 por ciento de la población mundial, y en la búsqueda de soluciones a esta enfermedad los sujetos son involucrados en diferentes tipos de estudios. En el presente trabajo se realiza una breve revisión de algunos aspectos éticos relacionados con la aprobación dada por los pacientes que padecen epilepsia o su representante legal para participar en estudios que presuponen la realización de exámenes diagnósticos y el empleo de formas novedosas de tratamiento, lo que se materializa a través del consentimiento informado. Especialmente, se hace referencia a la participación de los pacientes en ensayos clínicos y el manejo de las pacientes que quedan embarazadas en el transcurso del ensayo clínico, los efectos adversos de la medicación y de la cirugía de epilepsia(AU)

Medical Ethics addresses, among other aspects, the doctor-patient relationship from which the term informed consent is derived as its maximum expression. Epilepsy affects 1-2 percent of the world population, and in the search for solutions to this disease the subjects are involved in different types of studies. In the present paper, a brief review of some ethical aspects related to the approval given by patients suffering from epilepsy or their legal representative to participate in studies that presuppose the performance of diagnostic tests and the use of novel forms of treatment. This is materialized through informed consent. Especially, there is a reference to the participation of patients in clinical trials, and the management of patients who become pregnant during the clinical trial, the adverse effects of medication, and epilepsy surgery(AU)

Consentimiento informado en pacientes con epilepsias intratables / Informed consent in patients with intractable epilepsy

La ética médica aborda, entre otros aspectos, la relación médico-paciente, de la cual se deriva el término consentimiento informado como su máxima expresión. La epilepsia afecta al 1-2 por ciento de la población mundial, y en la búsqueda de soluciones a esta enfermedad los sujetos son involucrados en diferentes tipos de estudios. En el presente trabajo se realiza una breve revisión de algunos aspectos éticos relacionados con la aprobación dada por los pacientes que padecen epilepsia o su representante legal para participar en estudios que presuponen la realización de exámenes diagnósticos y el empleo de formas novedosas de tratamiento, lo que se materializa a través del consentimiento informado. Especialmente, se hace referencia a la participación de los pacientes en ensayos clínicos y el manejo de las pacientes que quedan embarazadas en el transcurso del ensayo clínico, los efectos adversos de la medicación y de la cirugía de epilepsia(AU)

Medical Ethics addresses, among other aspects, the doctor-patient relationship from which the term informed consent is derived as its maximum expression. Epilepsy affects 1-2 percent of the world population, and in the search for solutions to this disease the subjects are involved in different types of studies. In the present paper, a brief review of some ethical aspects related to the approval given by patients suffering from epilepsy or their legal representative to participate in studies that presuppose the performance of diagnostic tests and the use of novel forms of treatment. This is materialized through informed consent. Especially, there is a reference to the participation of patients in clinical trials, and the management of patients who become pregnant during the clinical trial, the adverse effects of medication, and epilepsy surgery(AU)

Relation of Structural and Functional Changes in Auditory and Visual Pathways after Temporal Lobe Epilepsy Surgery.

Auditory and visual pathways may be affected as a consequence of temporal lobe epilepsy surgery because of their anatomical relationships with this structure. The purpose of this paper is to correlate the results of the auditory and visual evoked responses with the parameters of tractography of the visual pathway, and with the state of connectivity between respective thalamic nuclei and primary cortices in both systems after the surgical resection of the epileptogenic zone in drug-resistant epileptic patients. Tractography of visual pathway and anatomical connectivity of auditory and visual thalamus-cortical radiations were evaluated in a sample of eight patients. In general, there was a positive relationship of middle latency response (MLR) latency and length of resection, while a negative correlation was found between MLR latency and the anatomical connection strength and anatomical connection probability of the auditory radiations. In the visual pathway, significant differences between sides were found with respect to the number and length of tracts, which was lower in the operated one. Anatomical connectivity variables and perimetry (visual field defect index) were particularly correlated with the latency of P100 wave which was obtained by quadrant stimulation. These results demonstrate an indirect functional modification of the auditory pathway and a direct traumatic lesion of the visual pathway after anterior temporal lobectomy in patients with drug resistant epilepsy.

Temporal lobe epilepsy surgery modulates the activity of auditory pathway.

The purpose of this paper is to evaluate the effects of the anterior temporal lobectomy on the functional state of the auditory pathway in a group of drug-resistant epileptic patients, linking the electrophysiological results to the resection magnitude. Twenty-seven patients with temporal lobe epilepsy and a matched control group were studied. Auditory brainstem and middle latency responses (ABR and MLR respectively) were carried out before and after 6, 12 and 24 months surgical treatment. The volume and longitude of temporo-mesial resected structures were estimated on magnetic resonance images taken 6 months after surgery. Before the intervention the patients showed a significant delay of latency in waves III, V, Pa and Nb, with an increase in duration of I-V interval in comparison with healthy subjects (Mann-Whitney U-test, p<0.05). After resection, additional significant differences in waves I and Na latency were observed. Na and Pa waveforms showed a tendency to increase in amplitude, which became statistically significant 12 months after surgery for right hemisphere lobectomized patients in the midline electrode, and in Pa waveform for all patients in the temporal electrodes ipsilateral to resection (Wilcoxon test, p<0.05). In general, latency variations of MLR correlated with resection longitude, while changes in amplitude correlated with the volume of the resection in the middle temporal pole and amygdala (Pearson' correlation test, p<0.05). As a result, we assume that anterior temporal lobectomy provokes functional modifications into the auditory pathway, probably related to an indirect modulation of its activity by the temporo-mesial removed structures.

Un método experimental para lesionar un nervio periférico y evaluar conductualmente la recuperación y el efecto de tratamientos restaurativos / An experimental method to injure a peripheral nerve and to evaluate recovery and the effect of restorative treatments using behavioral techniques

Se presenta un método simple de lesión del nervio periférico por pinzamiento del nervio ciático, y de evaluación conductual de la lesión y su recuperación empleando la marcha sobre una rejilla metálica. La lesión del ciático dificulta el desplazamiento de los animales sobre este sustrato como lo demuestran el aumento significativo de la latencia de escape hacia la caja de habitación y el incremento de fallos en el apoyo de la pata lesionada. Empleando este método se evaluó el efecto de la administración poslesional del complejo vitamínico Compvit B® y del ácido orótico (un precursor de nucleótidos de pirimidina) sobre la recuperación del nervio dañado. Ambos tratamientos y su combinación, mejoraron significativamente la recuperación del nervio lesionado al ser comparados con controles tratados con solución salina(AU)

The paper describes a simple method to injure the peripheral sciatic nerve by clamping, along with a behavioral test to asses the lesion and its recovery using the gait on a metallic grid. Sciatic nerve lesion impairs the displacement of the animals on this surface as demonstrated by the significant increase in the escape latency towards the room cage and the increased number of stance failures with the injured leg. Using this method we assessed the effect of post-injury administration of Compvit B® (vitamin compound) and orotic acid (a pyrimidine-nucleotide precursor) on the recovery of injured nerve. Both treatments and its combination, improved significantly the recovery of injured nerve compared to controls treated with saline solution(AU)

Un método experimental para lesionar un nervio periférico y evaluar conductualmente la recuperación y el efecto de tratamientos restaurativos / An experimental method to injure a peripheral nerve and to evaluate recovery and the effect of restorative treatments using behavioral techniques

Se presenta un método simple de lesión del nervio periférico por pinzamiento del nervio ciático, y de evaluación conductual de la lesión y su recuperación empleando la marcha sobre una rejilla metálica. La lesión del ciático dificulta el desplazamiento de los animales sobre este sustrato como lo demuestran el aumento significativo de la latencia de escape hacia la caja de habitación y el incremento de fallos en el apoyo de la pata lesionada. Empleando este método se evaluó el efecto de la administración poslesional del complejo vitamónico Compvit B® y del ácido orótico (un precursor de nucleótidos de pirimidina) sobre la recuperación del nervio dañado. Ambos tratamientos y su combinación, mejoraron significativamente la recuperación del nervio lesionado al ser comparados con controles tratados con solución salina

The paper describes a simple method to injure the peripheral sciatic nerve by clamping, along with a behavioral test to asses the lesion and its recovery using the gait on a metallic grid. Sciatic nerve lesion impairs the displacement of the animals on this surface as demonstrated by the significant increase in the escape latency towards the room cage and the increased number of stance failures with the injured leg. Using this method we assessed the effect of post-injury administration of Compvit B® (vitamin compound) and orotic acid (a pyrimidine-nucleotide precursor) on the recovery of injured nerve. Both treatments and its combination, improved significantly the recovery of injured nerve compared to controls treated with saline solution

Innovative evaluation of visual field defects in epileptic patients after standard anterior temporal lobectomy, using partial field visual evoked potentials.

The purpose of this paper is to obtain an electrophysiological evaluation of visual field defects consecutive to the direct lesion of optic radiations in drug-resistant epileptic patients after a standard electrocorticographically adjusted lobectomy, and to correlate it with conventional perimetric results, and with the volume of resected tissue during surgical treatment. Twenty-four patients with temporal lobe epilepsy defined through long term EEG-video, ictal and interictal SPECT, as well as Magnetic Resonance Imaging were studied. Visual evoked potentials (VEPs) with partial and total visual field stimulation were carried out before and after 6, 12 and 24 months surgical treatment. A control group was also studied. No differences between patients and control subjects were observed during the evaluation of the full-field VEPs. However, there were statistical differences between groups in the half-field VEP recordings and in the VEP recordings of contralateral to resected side superior quadrant (CSQ) before lobectomy and 6 months later (Mann-Whitney's U-test, p<0.05). Significant associations were found between VEP abnormalities and perimetric results in CSQ. A close relationship between perimetry, VEPs and volume of the resected tissue in hippocampus, parahippocampus, medial and lower temporal giri was also found. Visual field defects consecutive to standard temporal lobe resection in epileptic patients could be objectively evaluated by partial stimulation VEPs corresponding to the size of resected tissue.