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

Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Aspectos electroclínicos de la epilepsia temporal mesial / Neuropsychological risk in temporal lobe epilepsy

Introducción: La epilepsia del lóbulo temporal mesial se considera la más frecuente de las epilepsias focales, con signos y síntomas característicos que ayudan a definir su diagnóstico. Contenidos: Dentro de su historia natural, las crisis pueden iniciar en los primeros años de vida, usualmente como episodios febriles con un periodo de remisión, para reaparecer en la adolescencia o en el adulto joven. La presentación electroencefalográfica tiene un patrón característico, con aparición de puntas y ondas agudas interictales en la región temporal anterior, por lo general unilaterales, y con actividad ictal generalmente theta en la misma localización. La causa más frecuente es la esclerosis del hipocampo. El tratamiento con medicamentos anticrisis puede controlar la epilepsia, aunque algunos casos pueden evolucionar a la farmacorresistencia, en la cual la cirugía de epilepsia está indicada, y tiene buenos resultados. Conclusiones: Esta revisión se centra en la descripción de las características electroclínicas de la epilepsia temporal mesial, para hacer un diagnóstico temprano e iniciar un tratamiento adecuado, a efectos de lograr un mejor pronóstico y una mejor calidad de vida para los pacientes con epilepsia y sus familiares.

Introduction: Mesial temporal lobe epilepsy is considered the most common of the focal epilepsies, with characteristic signs and symptoms that help define its diagnosis. Contents: In the natural history of the disease, seizures can begin in the first years of life, usually as febrile seizures with a period of remission, to reappear in adolescence or in the young adult. The electroencephalographic presentation has a characteristic pattern with the appearance of interictal sharp waves and spikes in the anterior temporal region, usually unilateral, and with generally theta ictal activity in the same location. The most common cause is hippocampal sclerosis. Treatment with antiseizure medication can control epilepsy. However, in some cases evolution of drug resistance can occur, leading to epilepsy surgery as the most appropriate treatment, based on its good results. Conclusions: This review focuses on the description of the electroclinical characteristics of temporal mesial epilepsy, in order to make an early diagnosis and adequate treatment, thus providing a better prognosis and quality of life for patients with epilepsy and their families.

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)

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

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study

SUMMARY OBJECTIVE: Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. METHODS: This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. RESULTS: The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). CONCLUSIONS: The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy / 中华医学杂志(英文版)

BACKGROUND@#Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.@*METHODS@#We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.@*RESULTS@#The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance.@*CONCLUSION@#Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

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.

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

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.

Anatomical, radiological and clinical features of mesial temporal lobe epilepsy: two illustrated cases reports / Aspectos anatômicos, radiológicos e clínicos da epilepsia do lobo temporal mesial: relato ilustrado de dois casos

Mesial temporal lobe epilepsy is the most commom form of focal epilepsy in adults. Its clinical features include focal seizure, dysmnestic symptoms ­ such as déjà vu or jamais vu ­ and autonomic or psychic aura. We reported two cases of mesial temporal lobe epilepsy with similar clinical features, but with entirely different etiologies. Mesial temporal sclerosis contributes up to 70% of all mesial temporal lobe epilepsy cases and MRI usually shows reduced hippocampal volume and increased signal intensity on T2-weighted imaging. Incomplete hippocampal inversion has uncertain relation with epilepsy and is characterized by an atypical verticalized and medially positioned anatomical pattern of the hippocampus and also a deep collateral sulcus.

A epilepsia do lobo temporal mesial é a forma mais comum de epilepsia focal em adultos. Suas características clínicas incluem crises focais, sintomas dismnésicos - como déjà vu ou jamais vu - e aura autonômica ou psíquica. Relatamos dois casos de pacientes com epilepsia do lobo temporal mesial com manifestações clínicas semelhantes, mas com etiologias completamente diferentes. A esclerose mesial temporal contribui com até 70% de todos os casos de epilepsia do lobo temporal mesial e, geralmente, na ressonância magnética, apresenta atrofia do hipocampo e hipersinal na imagem ponderada em T2. A rotação incompleta do hipocampo possui uma relação incerta com a epilepsia e é caracterizada por alteração da estrutura interna do hipocampo, com um sulco colateral verticalizado e profundo.

History and Evolution of Epilepsy Surgery

The surgical treatment for epilepsy has a worldwide historical relevance for centuries. There are archaeological reports that date it back to ancient Egypt; however, the year 1886 is considered a landmark in the surgical treatment for epilepsy in theModern Age, when the first surgery for the treatment of focal epileptic events was performed successfully. Since then, innumerable related articles have been published evoluonarily. Over the last centuries, new techniques and technologies provided better understanding, diagnosis and management for this disease. Thus, historical and evolutionary knowledge becomes important to let us better understand the current position of the surgery for epilepsy treatment and control.

Spatiotemporal expression of RCAN1 and its isoform RCAN1-4 in the mouse hippocampus after pilocarpine-induced status epilepticus

Regulator of calcineurin 1 (RCAN1) can be induced by an intracellular calcium increase and oxidative stress, which are characteristic features of temporal lobe epilepsy. Thus, we investigated the spatiotemporal expression and cellular localization of RCAN1 protein and mRNA in the mouse hippocampus after pilocarpine-induced status epilepticus (SE). Male C57BL/6 mice were given pilocarpine hydrochloride (280 mg/kg, i.p.) and allowed to develop 2 h of SE. Then the animals were given diazepam (10 mg/kg, i.p.) to stop the seizures and sacrificed at 1, 3, 7, 14, or 28 day after SE. Cresyl violet staining showed that pilocarpine-induced SE resulted in cell death in the CA1 and CA3 subfields of the hippocampus from 3 day after SE. RCAN1 immunoreactivity showed that RCAN1 was mainly expressed in neurons in the shammanipulated hippocampi. At 1 day after SE, RCAN1 expression became detected in hippocampal neuropils. However, RCAN1 signals were markedly enhanced in cells with stellate morphology at 3 and 7 day after SE, which were confirmed to be reactive astrocytes, but not microglia by double immunofluorescence. In addition, real-time reverse transcriptase–polymerase chain reaction showed a significant upregulation of RCAN1 isoform 4 (RCAN1-4) mRNA in the SE-induced hippocampi. Finally, in situ hybridization with immunohistochemistry revealed astrocytic expression of RCAN1-4 after SE. These results demonstrate astrocytic upregulation of RCAN1 and RCAN1-4 in the mouse hippocampus in the acute and subacute phases of epileptogenesis, providing foundational information for the potential role of RCAN1 in reactive astrocytes during epileptogenesis.

A study of medial and lateral temporal lobe epilepsy based on stereoelectroencephalography / 中华医学杂志(英文版)

BACKGROUND@#Patients with temporal lobe epilepsy (TLE) originating from different seizure onset zones had distinct electrophysiological characteristics and surgical outcomes. In this study, we aimed to investigate the relationship between the origin and prognosis of TLE, and the stereoelectroencephalography (SEEG) features.@*METHODS@#Thirty patients with TLE, who underwent surgical treatment in our functional neurosurgery department from January 2016 to December 2017, were enrolled in this study. All patients underwent anterior temporal lobectomy after an invasive pre-operative evaluation with SEEG. Depending on the epileptic focus location, patients were divided into those with medial temporal lobe seizures (MTLS) and those with lateral temporal lobe seizures (LTLS). The Engel classification was used to evaluate operation effectiveness, and the Kaplan-Meier analysis was used to detect seizure-free duration.@*RESULTS@#The mean follow-up time was 25.7 ± 4.8 months. Effectiveness was 63.3% for Engel I (n = 19), 13.3% for Engel II, 3.3% for Engel III, and 20.0% for Engel IV. According to the SEEG, 60.0% (n = 18) had MTLS, and 40.0% (n = 12) had LTLS. Compared with the MTLS group, the operation age of those with LTLS was significantly greater (26.9 ± 6.9 vs. 29.9 ± 12.5 years, t = -0.840, P = 0.009) with longer epilepsy duration (11.9 ± 6.0 vs. 17.9 ± 12.1 years, t = -1.801, P = 0.038). Patients with MTLS had a longer time interval between ictal onset to seizure (67.3 ± 59.1 s vs. 29.3 ± 24.4 s, t = 2.017, P = 0.008). The most common SEEG ictal pattern was a sharp/spike-wave rhythm in the MTLS group (55.6%) and low-voltage fast activity in the LTLS group (58.3%). Compared with the LTLS group, patients with MTLS had a more favorable prognosis (41.7% vs. 77.8%, P = 0.049). Post-operative recurrence was more likely to occur within three months after the operation for both groups, and there appeared to be a stable long-term outcome.@*CONCLUSION@#Patients with MTLS, who accounted for three-fifths of patients with TLE, showed a more favorable surgical outcome.

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.

A Primer on Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Medically Refractory Epilepsy

Epilepsy surgery that eliminates the epileptogenic focus or disconnects the epileptic network has the potential to significantly improve seizure control in patients with medically intractable epilepsy. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been an established option for epilepsy surgery since the US Food and Drug Administration cleared the use of MRgLITT in neurosurgery in 2007. MRgLITT is an ablative stereotactic procedure utilizing heat that is converted from laser energy, and the temperature of the tissue is monitored in real-time by MR thermography. Real-time quantitative thermal monitoring enables titration of laser energy for cellular injury, and it also estimates the extent of tissue damage. MRgLITT is applicable for lesion ablation in cases that the epileptogenic foci are localized and/or deep-seated such as in the mesial temporal lobe epilepsy and hypothalamic hamartoma. Seizure-free outcomes after MRgLITT are comparable to those of open surgery in well-selected patients such as those with mesial temporal sclerosis. Particularly in patients with hypothalamic hamartoma. In addition, MRgLITT can also be applied to ablate multiple discrete lesions of focal cortical dysplasia and tuberous sclerosis complex without the need for multiple craniotomies, as well as disconnection surgery such as corpus callosotomy. Careful planning of the target, the optimal trajectory of the laser probe, and the appropriate parameters for energy delivery are paramount to improve the seizure outcome and to reduce the complication caused by the thermal damage to the surrounding critical structures.

Clinical Usefulness of Intraoperative Motor-Evoked Potential Monitoring during Temporal Lobe Epilepsy Surgery

BACKGROUND AND PURPOSE: We aimed to determine the effectiveness of intraoperative neurophysiological monitoring focused on the transcranial motor-evoked potential (MEP) in patients with medically refractory temporal lobe epilepsy (TLE). METHODS: We compared postoperative neurological deficits in patients who underwent TLE surgery with or without transcranial MEPs combined with somatosensory evoked potential (SSEP) monitoring between January 1995 and June 2018. Transcranial motor stimulation was performed using subdermal electrodes, and MEP responses were recorded in the four extremity muscles. A decrease of more than 50% in the MEP or the SSEP amplitudes compared with baseline was used as a warning criterion. RESULTS: In the TLE surgery group without MEP monitoring, postoperative permanent motor deficits newly developed in 7 of 613 patients. In contrast, no permanent motor deficit occurred in 279 patients who received transcranial MEP and SSEP monitoring. Ten patients who exhibited decreases of more than 50% in the MEP amplitude recovered completely, although two cases showed transient motor deficits that recovered within 3 months postoperatively. CONCLUSIONS: Intraoperative transcranial MEP monitoring during TLE surgery allowed the prompt detection and appropriate correction of injuries to the motor nervous system or ischemic stroke. Intraoperative transcranial MEP monitoring is a reliable modality for minimizing motor deficits in TLE surgery.

Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

Isolated effective coherence analysis of epileptogenic networks in temporal lobe epilepsy using stereo-electroencephalography / 生物医学工程学杂志

Stereo-electroencephalography (SEEG) is widely used to record the electrical activity of patients' brain in clinical. The SEEG-based epileptogenic network can better describe the origin and the spreading of seizures, which makes it an important measure to localize epileptogenic zone (EZ). SEEG data from six patients with refractory epilepsy are used in this study. Five of them are with temporal lobe epilepsy, and the other is with extratemporal lobe epilepsy. The node outflow (out-degree) and inflow (in-degree) of information are calculated in each node of epileptic network, and the overlay between selected nodes and resected nodes is analyzed. In this study, SEEG data is transformed to bipolar montage, and then the epileptic network is established by using independent effective coherence (iCoh) method. The SEEG segments at onset, middle and termination of seizures in Delta, Theta, Alpha, Beta, and Gamma rhythms are used respectively. Finally, the K-means clustering algorithm is applied on the node values of out-degree and in-degree respectively. The nodes in the cluster with high value are compared with the resected regions. The final results show that the accuracy of selected nodes in resected region in the Delta, Alpha and Beta rhythm are 0.90, 0.88 and 0.89 based on out-degree values in temporal lobe epilepsy patients respectively, while the in-degree values cannot differentiate them. In contrast, the out-degree values are higher outside the temporal lobe in the patient with extratemporal lobe epilepsy. Based on the out-degree feature in low-frequency epileptic network, this study provides a potential quantitative measure for identifying patients with temporal lobe epilepsy in clinical.