Epilepsia do lobo temporal com esclerose hipocampal mesial / Temporal lobe epilepsy with mesial hippocampal sclerosis / Epilepsia del lóbulo temporal con esclerosis del hipocampo mesial

Objetivo:Compreender o cenário atual da ELT-HS, caracterizado por sua fisiopatologia, manifestações clínicas, métodos diagnósticos e tratamentos. Método:Trata-se de uma revisão integrativa da literatura, com caráter descritivo, de artigos indexados no Sistema de Análise e Recuperação da Literatura Médica Online MEDLINE/Pubmed, Literatura Latino-Americana e do Caribe em Ciências da Saúde LILACS, e nas bases de dados Científicas Electronic Library Online (SciELO), pesquisados na período compreendido entre outubro de 2022 e março de 2023. Foram incluídos artigos em português e inglês que contemplassem os objetivos da revisão, publicados nos últimos dez anos (2011-2021).Resultados: Inicialmente foram encontrados 144 artigos nas bases de dados, que após a leitura, foramselecionados na pesquisa 40 artigos que correspondiam ao objetivo proposto. Os artigos analisados correspondem aos anos de 2011 a 2021. Conclusão:O tratamento cirúrgico da ELT-HS tem se mostrado eficaz para resolução completa das crises na maioria dos pacientes. O conhecimento sobre sua fisiopatologia, manifestações clínicas, diagnóstico e tratamentos são de fundamental importância para os médicos que atendem pacientes com epilepsia.

Objective: To understand the current scenario of TLE-HS, characterized by its pathophysiology, clinical manifestations, diagnostic methods and treatments. Method:This is an integrative literature review with descriptive character, of articles indexed in the Medical Literature Analysis And Retrieval System Online MEDLINE/Pubmed, Latin American and Caribbean Literature in Health Sciences LILACS, and Scientic databases Electronic Library Online (SciELO), researched in the period between october 2022 and march 2023. Articles in Portuguese and English that contemplated the objectives of the review, published in the last ten years (2011-2021), were included. Results:Initially, 144 articles were found in the databases, which after reading, 40 articles were selected in the research that corresponded to the proposed objective. The articles analyzed are equivalent to the years 2011 to 2021. Conclusion:The surgical treatment of TLE-HS has been shown to be effective for the complete resolution of crises in most patients. Knowledge about its pathophysiology, clinical manifestations, diagnosis and treatments are of fundamental importance for physicians who treat patients with epilepsy

Objetivo: Comprender el escenario actual de la TLE-HS, caracterizado por su fisiopatología, manifestaciones clínicas, métodos diagnósticos y tratamientos. Método: Se trata de una revisión bibliográfica integradora con carácter descriptivo, de artículos indexados en el Sistema de Análisis y Recuperación de Literatura Médica en Línea MEDLINE/Pubmed, Literatura Latinoamericana y del Caribe en Ciencias de la Salud LILACS, y bases de datos Scientic Electronic Library Online (SciELO), investigados en el período comprendido entre octubre de 2022 y marzo de 2023. Se incluyeron artículos en portugués e inglés que contemplaran los objetivos de la revisión, publicados en los últimos diez años (2011-2021). Resultados:Inicialmente se encontraron 144 artículos en las bases de datos, de los cuales luego de la lectura se seleccionaron 40 artículos en la investigación que correspondía al objetivo propuesto. Los artículos analizadoscorresponden a los años 2011 a 2021. Conclusión:El tratamiento quirúrgico del ELT-HS se ha mostrado eficaz para la resolución completa de las crisis en la mayoría de los pacientes. El conocimiento sobre su fisiopatología, manifestaciones clínicas, diagnóstico y tratamientos es de fundamental importancia para los médicos que tratan pacientes con epilepsia

开放科学(资源服务)标识码(OSID) Effect of Tanshinone ⅡA on abnormal integration of granule cells in the dentate gyrus of mice with chronic epilepsy / 西安交通大学学报(医学版)

【Objective】 To clarify the role and molecular mechanism of Tanshinone ⅡA (TanⅡA) in the pathological integration of granule cells in the dentate gyrus (DG) by using the mouse model of temporal lobe epilepsy (TLE). 【Methods】 Status epilepticus (SE) was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg. After two months, Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures. The DG was removed for staining of Timm, Prox-1, DCX and SynⅠ. PTEN, p-AKT, and p-S6 expressions were observed by Western blotting. 【Results】 TanⅡA decreased Timm score, SynⅠ, PSD-95 and pS6 levels, and increased the level of PTEN in the DG, and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells. Video surveillance showed that TanⅡA reduced the frequency of Racine’ grade 5 seizures. 【Conclusion】 TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.

Epilepsia del lóbulo temporal farmacorresistente como resultado de un programa quirúrgico / Drug-resistant temporal lobe epilepsy as a result of a surgical program

Introducción: La epilepsia del lóbulo temporal es la forma más común de epilepsia focal en el adulto y la que mejor responde al tratamiento quirúrgico. Objetivo: Identificar la asociación entre variables prequirúrgicas, transquirúrgicas y posquirúrgicas y la evolución en pacientes con epilepsia temporal farmacorresistente sometidos a cirugía de epilepsia. Métodos: Se estudiaron para la cirugía 24 pacientes con epilepsia temporal farmacorresistente, en el Instituto de Neurología y Neurocirugía, entre el año 2012 y 2020. Se utilizó el test de Fisher para identificar la asociación entre variables. Se evaluó la escala de Engel al año de la cirugía y en el último seguimiento. Resultados: Se alcanzó libertad de crisis (Engel I) en el 66,7 por ciento de los casos, según último seguimiento, con un período ente 1 a 8 años. La resección completa de la zona epileptogénica y la ausencia de crisis en los primeros 6 meses de la cirugía estuvieron relacionadas con Engel I al año y al último seguimiento. De igual forma las estadísticas estuvieron relacionadas: la ausencia de crisis posoperatorias agudas con Engel I al año y menos de 10 crisis al mes previo a la cirugía, la desaparición luego de la resección, del patrón epileptiforme encontrado en la electrocorticografía preresección, con Engel I al último seguimiento. Conclusiones: La mayoría de los pacientes operados de epilepsia del lóbulo temporal farmacorresistente quedaron libres de crisis en el último seguimiento. La resección completa de la zona epileptogénica y la ausencia de crisis en los primeros 6 meses de la cirugía estuvo asociada a las estadísticas de los resultados posquirúrgicos(AU)

Introduction: Temporal lobe epilepsy is the most common form of focal epilepsy in adults and the one that best responds to surgical treatment. Objective: to identify the association between pre-surgical, intra-surgical and post-surgical variables and evolution in patients with drug-resistant temporal epilepsy undergoing epilepsy surgery. Methods: Twenty four (24) patients with drug-resistant temporal epilepsy were studied for surgery at the Institute of Neurology and Neurosurgery, from 2012 to 2020. Fisher's test was used to identify the association between variables. The Engel scale was evaluated one year after surgery and at the last follow-up. Results: Seizure freedom (Engel I) was achieved in 66.7 percent of the cases, according to the last follow-up, with a period between 1 and 8 years. The complete resection of the epileptogenic zone and the absence of seizures in the first 6 months after surgery were related to Engel I at one year and at the last follow-up. In the same way, the statistics were related the absence of acute postoperative crises with Engel I a year and less than 10 crises a month prior to surgery, the disappearance, after resection, of the epileptiform pattern found in the pre-resection electrocorticography, with Engel I at last follow-up. Conclusions: The majority of patients operated on for drug-resistant temporal lobe epilepsy were seizure-free at the last follow-up. The complete resection of the epileptogenic zone and the absence of crises in the first 6 months after surgery were associated with the statistics of the postoperative results(AU)

Clinical analysis of 32 cases of temporal lobe epilepsy treated by microsurgery under intraoperative cortical EEG monitoring / 中国综合临床

Objective:To investigate the effect of microsurgery by modified pterional approach in the treatment of temporal lobe epilepsy under intraoperative cortical encephalon electricity graph (EEG) monitoring.Methods:The clinical data of 32 patients with temporal lobe epilepsy who were admitted to the Department of Neurosurgery of Shangqiu First People's Hospital from January 2012 to June 2021 were retrospectively analyzed, all patients underwent microsurgical resection of epileptogenic foci by modified pterional approach under cortical EEG monitoring.Results:The postoperative follow-up was from half a year to 6 years. According to the Tan's classification, 25 cases (78.1%(25/32)) of seizures disappeared completely, 3 cases (9.4%(3/32)) of seizures decreased by more than 75%, and 4 cases (12.5%(4/32)) of seizures decreased by more than 50%. Isotropic hemianopia occurred in 1 case (3.1%) after operation, and there was no operative death.Conclusion:Microsurgical resection of epileptogenic foci through modified pterional approach under intraoperative cortical EEG monitoring was a safe and effective method for the treatment of temporal lobe epilepsy.

N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline, the major bioactive compound from Sideroxylon obtusifolium, attenuates pilocarpine-induced injury in cultured astrocytes

Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 μg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.

Rehabilitación neuropsicológica en pacientes pre y posquirúrgicos de lobectomía temporal por epilepsia fármaco resistente / Neuropsychological rehabilitation in pre- and post-surgical temporal lobectomy patients for drug-resistant epilepsy

Introducción. La epilepsia del lóbulo temporal suele producir déficits mnésicos, atencionales y del lenguaje. En la mayoría de los casos, se trata con fármacos an-tiepilépticos, pero falla en un tercio de ellos. Por tal razón, una opción terapéutica es la lobectomía temporal, que contribuye a menguar las crisis. Sin embargo, los procedimientos quirúrgicos pueden conllevar secuelas, entre ellas consecuencias a nivel cognitivo. Para contrarrestar dichos efectos, se acostumbra llevar a cabo una rehabilitación neuropsicológica que va en pro de recuperar, fortalecer y sostener en el tiempo habilidades que ya venían afectándose desde antes de la cirugía. Objetivo. Brindar una reflexión en torno a la intervención neuropsicológica de la epilepsia en el lóbulo temporal. Método. La reflexión sobre el tema parte de un interés clínico y posteriormente se fue ampliando a partir de la revisión de la literatura en diferentes bases de datos como PubMed, Medline y Scopus entre los años 2000 y 2021. Reflexión. Son amplias las opciones terapéuticas a nivel neuropsicológico y pueden contribuir de manera positiva en la recuperación del paciente, por lo cual los profe-sionales requieren conocer las posibilidades de ello para poder utilizar las estrategias más adecuadas según cada caso y brindar opciones que beneficien la calidad de vida, teniendo en cuenta que ninguna es más efectiva que otra. Conclusión. Como resultado, se presenta un panorama general de la rehabilitación neuropsicológica en pacientes pre y posquirúrgicos con lobectomía, haciendo énfasis en la rehabilitación neuropsicológica tradicional y la rehabilitación basada en inteli-gencia artificial, realidad virtual y computación

Introduction. Temporal lobe epilepsy usually produces mnestic, attentional, and language deficits. In most cases, it is treated with antiepileptic drugs, but one third of them fail, so one therapeutic option is temporal lobectomy, which helps to reduce seizures. However, surgical procedures can have sequelae, including cognitive con-sequences. To counteract these effects, neuropsychological rehabilitation is usually carried out in order to recover, strengthen, and sustain in time skills that were already affected before the surgery. Objective. To provide a reflection on the neuropsychological intervention of tem-poral lobe epilepsy. Method. The reflection on the subject starts from a clinical interest and was sub-sequently expanded from the review of the literature in different databases such as PubMed, Medline, and Scopus between 2000 and 2021. Reflection. There are many therapeutic options at the neuropsychological level and they can contribute positively to the patient's recovery, so professionals need to know the possibilities in order to use the most appropriate strategies according to each case and provide options that benefit the quality of life, taking into account that none is more effective than the other one.Conclusion. As a result, an overview of neuropsychological rehabilitation in pre- and post-surgical patients with lobectomy is presented, with emphasis on traditional neuropsychological rehabilitation and rehabilitation based on artificial intelligence, virtual reality, and computation

Effect of pregabalin on sleep structure of rats with temporal lobe epilepsy / 中华行为医学与脑科学杂志

Objective:To explore the effect of pregabalin on sleep structure in rats with temporal lobe epilepsy induced by pilocarpine.Methods:Twelve adult SD rats (half male and half female) were injected intraperitoneally with pilocarpine to establish a chronic temporal lobe epilepsy model.According to the principle of gender matching, they were divided into model group and pregabalin group, with 6 rats in each group(half male and half female). Another 6 SD rats (half male and half female) were taken as the control group.The skull electrodes were placed in the brain areas of rats to monitor the cerebral electrical activity, then recorded the data after resting for 1 week.Rats in pregabalin group were intraperitoneally injected with 50 mg/kg pregabalin while the rats in model group and control group were intraperitoneally injected with equal volume of normal saline.Fifteen minutes later, video electroencephalogram(EEG) and electromyogram(EMG) of rats in each group were recorded.The recording time was from 10∶00 to 17∶00 for 2 consecutive days.The seizure frequency, EEG and EMG were obtained.SPSS 25.0 was used for data analysis, one-way ANOVA was used for multi group comparison, and Tukey test and Games-Howell test were used for further pairwise comparison.Results:(1)The frequency of seizures in the pregabalin group (0.0(0.0, 1.0)times) were significantly lower than that in the model group(2.5(1.0, 4.8)times)( Z=-3.0, P<0.05). (2)During the 7 h recording period, the analyzed data showed that there were significant differences in the sleep-wake transition frequency, slow-wave sleep(SWS) phase duration, rapid eye movement (REM) sleep phase duration, total SWS time, total REM time and total sleep time among the three groups( F=10.5, 4.1, 13.0, 7.8, 4.4, 9.3, all P<0.05). The frequency of sleep-wake transitions in the pregabalin group ((66.3±18.0) times) and the control group ((87.8±14.1) times) were less than that in the model group ((106.7±20.8) times) (both P<0.05). The duration of SWS phase ((11.2±4.0) min) in pregabalin group was significantly longer than that in model group ((5.9±1.8) min) ( P<0.05), while that in model group was shorter than that in control group ((7.7±1.2) min) ( P<0.05). The duration of REM phase in the model group ((1.9±0.4) min) was shorter than that in the control group ((2.5±0.4) min) ( P<0.05). There was no significant difference in the duration of REM phase between the pregabalin group and the model group ( P>0.05). Within 7 h of observation, the total SWS time ((296.5±37.1) min) and total sleep time ((338.4±33.3) min) in pregabalin group were longer than those in model group ((258.1±38.4) min, (288.9±41.0) min) (both P<0.05). The total REM time ((30.4±11.1) min) and total sleep time ((288.9±41.0) min) in the model group were significantly shorter than those in the control group ((50.2±8.5) min, (339.0±19.6) min) (both P<0.05). Conclusion:Pregabalin alone can reduce seizures and change the sleep structure disorder caused by epilepsy, which is mainly manifested in reducing the number of sleep-wake transitions, prolonging the duration of SWS, increasing sleep duration, increasing SWS and total sleep time and improving sleep quality.

Correlation between thalamic network abnormity and cognitive function in patients with temporal lobe epilepsy / 中华行为医学与脑科学杂志

Objective:To explore the correlation and mechanism between thalamic network abnormality and cognitive decline in patients with temporal lobe epilepsy (TLE).Methods:A total of 53 patients with unilateral TLE were consecutively enrolled through the epilepsy clinic of the First Affiliated Hospital of Guangxi Medical University from December 2018 to February 2020. During the same recruitment interval, 37 health controls(HC) with matching demographic characteristic were recruited. All subjects were received the Montreal cognitive assessment(MoCA) test and multimodal MRI scanning. Voxel-based morphometry method was used to study the changes of thalamic gray matter volume in patients with unilateral TLE. The structural covariance network and functional connectivity network based on seed points were used to analyze the changes of thalamic network in TLE patients. In addition, the correlations among abnormal thalamic structure, thalamic network and cognitive function score were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and Mann Whitney U test were used for inter group comparison. In order to explore the relationship between thalamus and thalamic network and cognitive performance in TLE patients, thalamic volume and gray matter volume and functional connection value of brain areas with abnormal synergistic changes were extracted and correlated with MoCA score. Results:The total score of MoCA in TLE patients (27.0(25.0, 29.0)) was significantly decreased compared with HC (29.0(28.0, 30.0))( Z=-4.601, P<0.001). Whole brain gray matter volume analysis showed that compared with HCTLE patients showed significant volume reduction in left cerebellum, right temporal pole, right fusiform gyrus, straight gyrus, bilateral middle temporal gyrus, thalamus, medial and paracingulate gyrus (GRF adjusted, voxel-level P<0.001 and cluster-level P<0.05). The thalamus-associated structural covariance network analysis revealed that compared with healthy controls, TLE patients exhibited decreased connectivity in right fusiform gyrus (MNI: x=28.5, y=-15.0, z=-34.5), left insula (MNI: x=-33.0, y=-18.0, z=-1.5), right middle temporal gyrus (MNI: x=55.5, y=-51.0, z=9.0), left complementary motor area (MNI: x=-10.5, y=1.5, z=57.0) and right posterior central gyrus (MNI: x=31.5, y=-33.0, z=51.0) ( P<0.001, cluster > 100). The thalamus-associated functional connectivity network analysis revealed that TLE patients exhibited decreased connectivity in left insula (MNI: x=-38, y=-7, z=-7), left lingual gyrus (MNI: x=-6, y=-81, z=-12), right lingual gyrus (MNI: x=15, y=-105, z=0) and left triangular inferior frontal gyrus (MNI: x=-39, y=36, z=-6) (GRF correction, voxel-level P<0.001 and cluster-level P<0.05). Volume of left insula which had decreased structural connectivity with thalamus were positively correlated with the MoCA score in TLE patients( r=0.279, P=0.043). Volume of left complementary motor area which had decreased structural connectivity with thalamus was positively correalated with the MoCA score and language score in TLE patients( r=0.323, P=0.018; r=0.334, P=0.015). Volume of left lingual gyrus which had decreased functional connectivity with thalamus was negatively correalated with the memory score in TLE patients ( r=-0.331, P=0.016). Conclusion:Thalamic volume, thalamic structural covariant network and functional connection network are changed in TLE patients. The abnormality of thalamic network is associated with cognitive performance in TLE patients, which may be the neural mechanism of thalamus participating in the cognitive impairment of TLE patients.

Quiste cerebral como complicación tardía inusual de lobectomía temporal en epilepsia farmacorresistente: reporte de un caso / Brain cyst as an unusual delayed complication of temporal lobectomy in drug-resistant epilepsy: a case report

RESUMEN La lobectomía temporal anterior es una técnica que ha probado, con un muy alto nivel de evidencia (60-73% de los casos), alcanzar un estado libre de convulsiones en pacientes con epilepsia focal farmacorresistente del lóbulo temporal. Se trata de una técnica que aun cuando ha demostrado ser segura, no está del todo libre de complicaciones. Se han reportado, por ejemplo, cuadrantanopsia homónima superior y depresión como las complicaciones más frecuentes, en tanto que la ocurrencia de un quiste cerebral sintomático de instauración tardía es muy poco usual. Se describe el caso de una paciente sometida a lobectomía temporal derecha que presentó esta infrecuente complicación, y se incluyen una pertinente revisión de la literatura y mecanismos fisiopatogénicos propuestos.

SUMMARY Anterior temporal lobectomy is a technique that has proven, with a very high level of evidence (60-73% of the cases), to reach a seizure-free status in patients with drug-resistant focal temporal lobe epilepsy. It is a technique that although generally safe, cannot be considered entirely free of complications. Superior homonymus quadrantanopsia and depression have been reported, for instance, as the most frequent complications. While the occurrence of a late-onset symptomatic brain cyst, is very rare. The case of a patient who was subjected to right temporal lobectomy and presented this unusual complication is described here, with inclusion of a review ofpertinent literature and proposed pathophysiological mechanisms.

Esclerose Mesial Temporal: Prevalência em um ambulatório de referência no Hospital Universitário Professor Polydoro Ernani de São Thiago / Mesial Temporal Sclerosis: Prevalence study in a reference outpatient clinic at Hospital Universitário Professor Polydoro Ernani de São Thiago

A epilepsia é uma doença heterogênea com alto impacto global, principalmente dentre aquelas pessoas com pobre controle clínico. Um de seus espectros é a esclerose mesial temporal, um tipo de epilepsia do lobo temporal cuja etiologia é estrutural e se caracteriza por lesões hipocampais uni ou bilaterais. Esta é a causa mais comum de epilepsia do lobo temporal farmacorresistente. Em cerca de 2/3 dos casos, ela é relacionada a um nível insatisfatório de controle clínico mediante medidas farmacológicas. Contudo, existe uma opção terapêutica adequada para o controle de crises nesta patologia, a intervenção cirúrgica. O presente trabalho trata-se de um estudo descritivo observacional transversal o qual visa analisar a prevalência da esclerose mesial temporal e o perfil epidemiológico dos pacientes acompanhados no ambulatório de referência do Hospital Universitário Professor Polydoro Ernani de São Thiago. Mais de 80% destes possuem epilepsia resistente a medicamentos, porém apenas 22% deles foram submetidos à cirurgia. Além disso, os pacientes apresentaram um convívio médio de 34 anos com a doença. Diante disso, propõe-se uma discussão acerca dos motivos da baixa disponibilidade da terapia cirúrgica para esclerose mesial temporal e o impacto dessa condição em nossa realidade.

Epilepsy is a heterogeneous disease with a high impact, mainly among those patients who have poorly controlled seizures. The most common cause of pharmacoresistant epilepsy is mesial temporal lobe epilepsy associated with uni or bilateral hippocampal sclerosis. Approximately 60% of the cases, it is related to unsatisfactory clinical control through pharmacological measuresis refractory to pharmacological treatment. However, there is an effective and safe therapeutic option, although still heavily underutilized, which is surgical therapy. This is a cross-sectional observational study, which aimed to analyze the prevalence of mesial temporal sclerosis and the epidemiological profile of these patients at the outpatient clinic of Hospital Universitário Professor Polydoro Ernani de São Thiago. Among the participants, more than 80% of those were considered drug resistant epilepsy, however, only 22% of them were submitted to surgery. Additionally, the patients had an average of 34 year of disease duration. In light of this, we discussed the main reasons for this surgical gap for mesial temporal sclerosis, and the impact of this persistent underutilization of surgical therapy in Brazil.

Correlation between 1H-MRS metabolites in hippocampal and T lymphocyte subsets and cytokines in peripheral blood of patients with temporal lobe epilepsy / 中华行为医学与脑科学杂志

Objective:To analyze the correlation between 1H-MRS in hippocampus and peripheral blood cytokines and T lymphocyte subsets in patients with temporal lobe epilepsy, and to explore the relationship between immune dysfunction and the degree of neuronal injury. Methods:Fifty patients with temporal lobe epilepsy were selected from Affiliated Hospital of Xuzhou Medical University from October 2020 to July 2021.Clinical data of all patients were collected and they were divided into two groups according to MRI results of epileptic sequence: abnormal hippocampal MRI group ( n=20) and normal hippocampal MRI group ( n=30). Bilateral 1H-MRS scanning of hippocampal and detection of T lymphocyte subsets and cytokines in peripheral blood during interictal period were performed in both groups. The levels of hippocampal metabolites NAA, NAA/(Cr+ Cho), T lymphocyte subsets and cytokines in peripheral blood of the two groups were compared.At the same time, the levels of NAA and NAA/ (Cr+ Cho) in the hippocampus on the abnormal side and the normal side in the abnormal hippocampal MRI group were compared within the group. Finally, the correlation between the levels of metabolites NAA, NAA/ (Cr+ Cho) in the hippocampus on the abnormal side obtained by 1H-MRS scanning and T lymphocyte subsets and cytokines in the abnormal group of MRI was analyzed. The data were statistically analyzed by SPSS 26.0 software. Independent sample t-test or Mann-Whitney U test was used for comparison between the two groups. Paired sample t-test was used for intra group comparison of different sides. Spearman correlation analysis was used to analyze the correlation between each index. Results:The NAA and NAA/(Cr+ Cho) values of the abnormal MRI group(normal side NAA: (1.22±0.37), NAA/(Cr+ Cho): (0.56±0.15). abnormal side NAA: (1.02±0.34), NAA/(Cr+ Cho): (0.48±0.13)) were significantly lower than those of the normal MRI group (NAA: (1.51±0.36), NAA/(Cr+ Cho): (0.73±0.19))(NAA: t=2.705, 4.800, both P<0 05; NAA/(Cr+ Cho): t=3.394, 4.914, both P<0 05). The values of NAA and NAA/(Cr+ Cho) in the abnormal side in the MRI abnormal group were significantly lower than those in the normal side( t=6.467, P<0 05). The levels of IL-1β(11.19(3.56, 20.98)pg/ml), IL-5 (3.12(1.86, 6.41)pg/ml), TNF-α(2.55(1.19, 8.28)pg/ml), CD4+ T lymphocytes((43.13±6.82)%) and Th/Ts((1.96±0.66)) in the hippocampal MRI abnormal group were significantly higher than those in normal MRI group (IL-1β: 3.27(1.63, 6.17)pg/ml, IL-5: 1.15(0.96, 2.96)pg/ml, TNF-α: 1.34(1.02, 2.36)pg/ml, CD4+ T: (38.01±7.21)%, Th/Ts: (1.48±0.53))( Z=-3.041, -2.516, -2.496, all P<0.05; t=2.511, 2.810, both P<0 05). The level of CD8+ T ((23.48±5.33)%) in peripheral blood of abnormal MRI group was significantly lower than that of normal group CD8+ T((27.18±6.08)%)( t=2.210, P<0.05). In the abnormal MRI group, the levels of NAA and NAA/ (Cr+ Cho) in the abnormal hippocampus were negatively correlated with the levels of IL-1β, IL-5 and TNF- α ( r=-0.612--0.463, all P<0.05), and positively correlated with CD8+ T lymphocytes ( r=0.537, 0.478, P<0.05). Conclusion:There is neuronal damage and dysfunction in the abnormal hippocampal region of patients with temporal lobe epilepsy with abnormal hippocampal formation, and the degree of neuronal damage is highly correlated with CD8+ T lymphocytes, IL-5, IL-1β and TNF-α in peripheral blood. The imbalance of interictal lymphocyte subsets and chronic inflammatory response may play an important role in the pathogenesis of epilepsy and neuronal injury .

Optimized multi-scale entropy to localize epileptogenic hemisphere of temporal lobe epilepsy based on resting-state functional magnetic resonance imaging / 生物医学工程学杂志

Entropy model is widely used in epileptic electroencephalogram (EEG) analysis, but there are few reports on how to objectively select the parameters to compute the entropy model in the analysis of resting-state functional magnetic resonance imaging (rfMRI). Therefore, an optimization algorithm to confirm the parameters in multi-scale entropy (MSE) model was proposed, and the location of epileptogenic hemisphere was taken as an example to test the optimization effect by supervised machine learning. The rfMRI data of 20 temporal lobe epilepsy (TLE) patients with hippocampal sclerosis, positive on structural magnetic resonance imaging, were divided into left and right groups. Then, the parameters in MSE model were optimized by the receiver operating characteristic curves (ROC) and area under ROC curve (AUC) values in sensitivity analysis, and the entropy value of the brain regions with statistically significant difference between the groups were taken as sensitive features to epileptogenic hemisphere lateral. The optimized entropy values of these bio-marker brain areas were considered as feature vectors input into the support vector machine (SVM). Finally, combining optimized MSE model with SVM could accurately distinguish epileptogenic hemisphere in TLE at an average accuracy rate of 95%, which was higher than the current level. The results show that the MSE model parameter optimization algorithm can accurately extract the functional imaging markers sensitive to the epileptogenic hemisphere, and achieve the purpose of objectively selecting the parameters for MSE in rfMRI, which provides the basis for the application of entropy in advanced technology detection.

Feature of cognitive dysfunction in patients with temporal lobe epilepsy and its clinical influencing factors / 中南大学学报(医学版)

OBJECTIVES@#To comprehensively analyze the characteristics of cognitive impairment of temporal lobe epilepsy (TLE), and to explore the effects of different lateral patients' cognitive impairment and different clinical factors on cognitive impairment of TLE.@*METHODS@#A total of 84 patients, who met the diagnostic criteria for TLE in the Department of Neurology, Xiangya Hospital, were collected as a patient group, with 36 cases of left TLE and 48 cases of right TLE. A total of 79 healthy volunteers with matching gender, age and education level were selected as a control group. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the scores of Arithmetic Test, Information Test, Digit Symbol Substitution Test (DSST), Block Design Test (BDT), Hayling Test and Verbal Fluency Test (VFT) of the revised Chinese Adult Wechsler Intelligence scale were retrospectively analyzed in the 2 groups.Multiple regression analysis was used to analyze the relationship between the clinical factors and the cognitive impairment score.@*RESULTS@#Compared with the control group, the TLE patient group had low scores in all neuropsychological tests, with significant difference (all @*CONCLUSIONS@#There are multiple cognitive domain dysfunctions in TLE, including language, short-term memory, long-term memory, attention, working memory, executive function and visual space function. Left TLE has greater impairment of executive function and right TLE has greater damage in working memory. Long pathography of disease, hippocampal sclerosis and a history of febrile convulsions may lead to more severe cognitive impairment. Earlier identification and earlier intervention are needed to improve prognosis of patients.

Evaluation of memory in persons with mesial temporal lobe sclerosis: A combined fMRI and VBM study

Persons with drug refractory TLE have the option of being managed by surgery. They may develop memoryimpairment with specific etiology of mesial temporal sclerosis and anterior temporal lobe resection (ATLR).The study evaluated the semantic verbal memory outcomes in pre- and post-surgery temporal lobe epilepsy(TLE) patients using functional MRI and voxel morphometric methods. Twenty consecutive persons withdrug-resistant epilepsy (DRE) and 20 healthy controls were recruited after obtaining the institute ethicsapproval. The fMRI scans were performed on a 1.5 T MR Scanner using standardized semantic verbal memorytasks using a native Hindi paradigm, before and after an anterior temporal lobectomy (in cases). A task-basedfunctional connectivity (FC) was estimated using a conn toolbox. Data analysis was carried out using thestatistical parametric imaging (SPM12) and CAT12 toolbox. Post-surgery TLE group showed increased robustFC in the right middle and posterior temporal regions as compared to pre-surgery session. A significantreduction in grey matter volume was observed in the left temporal lobe post-operatively as compared to presurgery and healthy control groups. In the post-surgery TLE group, neuropsychological scores were reduced inspecific PGI domains such as visuospatial, working memory, and executive functioning. Our results may helpin understanding of memory reorganization in TLE post-operatively.

An intensive education program for caregivers ameliorates anxiety, depression, and quality of life in patients with drug-resistant temporal lobe epilepsy and mesial temporal sclerosis who underwent cortico-amygdalohippocampectomy

This study aimed to investigate the effect of a caregiver intensive education program (CIEP) on anxiety, depression, and quality of life (QOL) in patients with drug-resistant temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) who underwent cortico-amygdalohippocampectomy (CAH). Ninety patients with drug-resistant TLE-MTS who underwent CAH and their caregivers were recruited and randomly allocated to the CIEP group or control group as 1:1 ratio. Caregivers received the CIEP program or routine guidance/education (control group). Anxiety/depression and QOL in patients at month (M)0, M1, M3, and M6 were assessed by the Hospital Anxiety and Depression Scale (HADS) scale and the QOL in Epilepsy Inventory-31 (QOLIE-31), respectively. Treatment efficacy at M6 was assessed by Engel classification. The HADS-anxiety score at M3 (P=0.049) and M6 (P=0.028), HADS-anxiety score change (M6-M0) (P=0.001), percentage of anxiety patients at M6 (P=0.025), and anxiety severity at M6 (P=0.011) were all decreased in the CIEP group compared with the control group. The HADS-depression score at M6 (P=0.033) and HADS-depression score change (M6-M0) (P=0.022) were reduced, while percentage of depression patients at M6 (P=0.099) and depression severity at M6 (P=0.553) showed no difference in the CIEP group compared with the control group. The QOLIE-31 score at M6 (P=0.043) and QOLIE-31 score change (M6-M0) (P=0.010) were both elevated in the CIEP group compared with the control group. In conclusion, CIEP for caregivers contributed to the recovery of anxiety and depression as well as the improvement of QOL in patients with drug-resistant TLE-MTS who underwent CAH.

SAD-B modulates epileptic seizure by regulating AMPA receptors in patients with temporal lobe epilepsy and in the PTZ-induced epileptic model

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the predominant mediators of glutamate-induced excitatory neurotransmission. It is widely accepted that AMPA receptors are critical for the generation and spread of epileptic seizure activity. Dysfunction of AMPA receptors as a causal factor in patients with intractable epilepsy results in neurotransmission failure. Brain-specific serine/threonine-protein kinase 1 (SAD-B), a serine-threonine kinase specifically expressed in the brain, has been shown to regulate AMPA receptor-mediated neurotransmission through a presynaptic mechanism. In cultured rat hippocampal neurons, the overexpression of SAD-B significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Here, we showed that SAD-B downregulation exerted antiepileptic activity by regulating AMPA receptors in patients with temporal lobe epilepsy (TLE) and in the pentylenetetrazol (PTZ)-induced epileptic model. We first used immunoblotting and immunohistochemistry analysis to demonstrate that SAD-B expression was increased in the epileptic rat brain. Subsequently, to explore the function of SAD-B in epilepsy, we used siRNA to knock down SAD-B protein and observed behavior after PTZ-induced seizures. We found that SAD-B downregulation attenuated seizure severity and susceptibility in the PTZ-induced epileptic model. Furthermore, we showed that the antiepileptic effect of SAD-B downregulation on PTZ-induced seizure was abolished by CNQX (an AMPA receptor inhibitor), suggesting that SAD-B modulated epileptic seizure by regulating AMPA receptors in the brain. Taken together, these findings suggest that SAD-B may be a potential and novel therapeutic target to limit epileptic seizures.

Clinical characteristics of nonlesional temporal lobe epilepsy / 中华神经科杂志

Objective@#To investigate the clinical characteristics, memory and neuroimaging features of nonlesional temporal lobe epilepsy (TLE-NL).@*Methods@#Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017. The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS. Twenty healthy volunteers were also recruited. Memory assessment and high resolution magnetic resonance imaging (MRI) scanning were completed in the patients and healthy volunteers. Volume and shape of the hippocampus were compared between patients and healthy volunteers.@*Results@#Compared with the TLE-HS, TLE-NL patients showed later seizure onset ((24.3±12.6) vs (15.8±10.3) years; t=3.684, P<0.01), shorter duration of epilepsy ((4.00 (2.00, 8.75)) vs (14.00 (7.50, 22.00)) years; Z=-4.675, P<0.01), less history of febrile convulsions (4.5% (2/44) vs 62.3% (33/53); χ2=32.270, P<0.01) and lower incidence of pharmacoresistant epilepsy (47.7% (21/44) vs 84.9% (45/53); χ2=15.282, P<0.01). However, there were no statistically significant differences between TLE-NL and TLE-HS in sex ratio, family history of epilepsy, lateralization of the epileptogenic zone, presence of aura, seizure types and seizure frequency. TLE-NL patients had normal memory quotient compared to normal controls (105.2±17.4 vs 103.8±16.2; P=1.000), while TLE-HS patients had significant memory impairment compared to normal controls (84.5±20.3 vs 103.8±16.2; P<0.01). Compared to normal controls, TLE-NL patients did not have significant alteration in hippocampal volume and shape, while TLE-HS patients had significant atrophy in the ipsilateral hippocampus ((2 953±481) mm3 vs (4 431±505) mm3; P<0.01), and shape analysis showed significant atrophy in the head and body of the hippocampus.@*Conclusion@#TLE-NL has different characteristics compared with TLE-HS, including later seizure onset, shorter duration of epilepsy, less history of febrile convulsions, better response to antiepileptic drugs, and no significant memory impairment and hippocampal atrophy.

Clinical characteristics of nonlesional temporal lobe epilepsy / 中华神经科杂志

Objective@#To investigate the clinical characteristics, memory and neuroimaging features of nonlesional temporal lobe epilepsy (TLE-NL).@*Methods@#Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017. The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS. Twenty healthy volunteers were also recruited. Memory assessment and high resolution magnetic resonance imaging (MRI) scanning were completed in the patients and healthy volunteers. Volume and shape of the hippocampus were compared between patients and healthy volunteers.@*Results@#Compared with the TLE-HS, TLE-NL patients showed later seizure onset ((24.3±12.6) vs (15.8±10.3) years; t=3.684, P<0.01), shorter duration of epilepsy ((4.00 (2.00, 8.75)) vs (14.00 (7.50, 22.00)) years; Z=-4.675, P<0.01), less history of febrile convulsions (4.5% (2/44) vs 62.3% (33/53); χ2=32.270, P<0.01) and lower incidence of pharmacoresistant epilepsy (47.7% (21/44) vs 84.9% (45/53); χ2=15.282, P<0.01). However, there were no statistically significant differences between TLE-NL and TLE-HS in sex ratio, family history of epilepsy, lateralization of the epileptogenic zone, presence of aura, seizure types and seizure frequency. TLE-NL patients had normal memory quotient compared to normal controls (105.2±17.4 vs 103.8±16.2; P=1.000), while TLE-HS patients had significant memory impairment compared to normal controls (84.5±20.3 vs 103.8±16.2; P<0.01). Compared to normal controls, TLE-NL patients did not have significant alteration in hippocampal volume and shape, while TLE-HS patients had significant atrophy in the ipsilateral hippocampus ((2 953±481) mm3 vs (4 431±505) mm3; P<0.01), and shape analysis showed significant atrophy in the head and body of the hippocampus.@*Conclusion@#TLE-NL has different characteristics compared with TLE-HS, including later seizure onset, shorter duration of epilepsy, less history of febrile convulsions, better response to antiepileptic drugs, and no significant memory impairment and hippocampal atrophy.

Clinical characteristics of nonlesional temporal lobe epilepsy / 中华神经科杂志

Objective To investigate the clinical characteristics,memory and neuroimaging features of nonlesional temporal lobe epilepsy (TLE-NL).Methods Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017.The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS.Twenty healthy volunteers were also recruited.Memory assessment and high resolution magnetic resonance imaging(MRI) scanning were completed in the patients and healthy volunteers.Volume and shape of the hippocampus were compared between patients and healthy volunteers.Results Compared with the TLE-HS,TLE-NL patients showed later seizure onset ((24.3± 12.6) vs (15.8± 10.3) years;t=3.684,P＜0.01),shorter duration of epilepsy ((4.00 (2.00,8.75)) vs (14.00 (7.50,22.00)) years;Z=-4.675,P＜0.01),less history of febrile convulsions (4.5％ (2/44) vs 62.3％ (33/53);x2=32.270,P＜0.01) and lower incidence of pharmacoresistant epilepsy (47.7％ (21/44) vs 84.9％ (45/53);x2=15.282,P＜0.01).However,there were no statistically significant differences between TLE-NL and TLE-HS in sex ratio,family history of epilepsy,lateralization of the epileptogenic zone,presence of aura,seizure types and seizure frequency.TLE-NL patients had normal memory quotient compared to normal controls (105.2± 17.4 vs 103.8± 16.2;P=1.000),while TLE-HS patients had significant memory impairment compared to normal controls (84.5 ± 20.3 vs 103.8± 16.2;P＜0.01).Compared to normal controls,TLE-NL patients did not have significant alteration in hippocampal volume and shape,while TLE-HS patients had significant atrophy in the ipsilateral hippocampus ((2 953±481) mm3vs (4 431±505) mm3;P＜0.01),and shape analysis showed significant atrophy in the head and body of the hippocampus.Conclusion TLE-NL has different characteristics compared with TLE-HS,including later seizure onset,shorter duration of epilepsy,less history of febrile convulsions,better response to antiepileptic drugs,and no significant memory impairment and hippocampal atrophy.

Observation of Therapeutic Efficacy of Oxcarbazepine Combined with Levetiracetam in the Treatment of Cognitive Dysfunction in Adult Patients with Temporal Lobe Epilepsy / 中国药房

OBJECTIVE：To observe therapuetic effica cy of oxcarbazepine combined with levetiracetam in the treatment of cognitive dysfunction in adult patients with temporal lobe epilepsy. METHODS ：According to inclusion and exclusion criteria ，83 adult patients with temporal lobe epilepsy were collected from neurology department of the First Affiliated Hospital of Kunming Medical University during January 2018 to October 2019，and then divided into control group （39 cases）and observation group （44 cases）. Control group was given Oxcarbazepine tablet with initial dose of 8-10 mg/（kg·d），morning and night ，increased by 5-10 mg/（kg·d）each week according to patient ’s condition ，the maximal dose was 45 mg/（kg·d），lasting for 3 months with the lowest effective treatment dose. Based on treatment of control group ，observation group was additionally given Levetiracetam tablet with initial dose of 5-10 mg/（kg·d），morning and night ，increased by 5-10 mg/（kg·d）each week according to the severity of disease，the total dose was not more than 2 000 mg/d，lasting for 3 months with the lowest effective treatment dose. The event-related potential P 300 at Pz site in 2 groups was measured before and after treatment （including the incubation period of N 1， P2，N2 and P 3 waves，amplitude of P 3 wave）. Webster ’s Adult Intelligence Scale [WAIS-RC ，including verbal IQ （VIQ）， performance IQ （PIQ），full scale IQ （FIQ）scores] and Clinical Memory Scale [CMS ，converting to memory quotient （MQ） score] were adopted. The occurrence of ADR was recorded. RESULTS ：Totally 5 patients of control group and 7 patients of observation group fell off. Finally ，a total of 71 patients participated in the entire study （34 cases in control group and 37 cases in observation group ）. Before treatment ，there was no statistical significance in P 300 at Pz site ，WAIS-RC and CMS between 2 groups （P＞0.05）. Compared with before treatment ，incubation period of N 2 and P 3 waves was shortenedsignificantly in 2 groups，and amplitude of P 3 wave wasincreased significantly after treatment （P＜0.05）；VIQ，FIQ and MQ scores were increased significantly （P＜0.05）. The incubation pe riod of P 2 wave was shortened significantly，and PIQ score was increased significantly in observation group （P＜ 0.05）. Compared with control group ，the shortening degree of incubation period of P 2，P3 waves，rising degree of amplitude of P 3 wave and rising degree of VIQ ，PIQ，FIQ，MQ scores were more bigger after treatment in observation （P＜0.05）. In the control group，there was 1 case of slight rash ，1 case of conscious asthenia ；in the observation group ，there was 1 case of nausea and vomiting，1 case of conscious asthenia ，and 1 case of emotional instability ；no serious ADR was found in 2 groups. CONCLUSIONS：Oxcarbazepine combined with levetiracetam can improve cognitive dysfunction in adult patients with temporal lobe epilepsy ，and the treatment effect is significantly better than oxcarbazepine monotherapy.