Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Predictive factors for successful vagus nerve stimulation in patients with refractory epilepsy: real-life insights from a multicenter study

Vagus nerve stimulation (VNS) therapy is an established treatment for patients with drug-resistant epilepsy that reduces seizure frequency by at least 50% in approximately half of patients; however, the characteristics of the patients with the best response have not yet been identified. Thus, it is important to identify the profile of patients who would have the best response to guide early indications and better patient selection.

A terapia com estimulação do nervo vago (ENV) é um tratamento estabelecido para pacientes com epilepsia resistente a medicamentos que reduz a frequência de crises em pelo menos 50% em aproximadamente metade dos pacientes; entretanto, as características dos pacientes com melhor resposta ainda não foram identificadas. Assim, é importante identificar o perfil de pacientes que teriam melhor resposta para orientar indicações precoces e melhor seleção de pacientes.

Factores asociados a epilepsia farmacorresistente en niños atendidos en un hospital de referencia nacional / Factors associated with drug-resistant epilepsy in children treated at a national referral hospital

Antecedentes: Según la Organización Mundial de la Salud (OMS) cerca de 70 millones de personas en el mundo padecen epilepsia. Los países de medianos y bajos ingresos presentan 70-80% de los casos; se estima que afecta 4-13% de los niños hasta los 16 años, de los cuales la epilepsia farmacorresistente (EFR) se desarrolla en 10-23%. Objetivo: Determinar factores de riesgo asociados a EFR en pacientes pediátricos atendidos en Hospital María, Especialidades Pediátricas (HMEP), Tegucigalpa, marzo 2017-marzo 2022. Métodos: Estudio de casos-controles. A partir del total de pacientes menores de 18 años con diagnóstico de epilepsia atendidos en el Servicio de Neurología HMEP, se definió Caso como pacientes con diagnóstico de EFR y Controles como pacientes con epilepsia no farmacorresistente (ENFR). A partir de expedientes clínicos, se evaluaron factores sociodemográficos, antecedentes personales y familiares, factores clínicos, estudios de imagen y electroencefalograma. El estudio fue aprobado por el Comité de Ética Institucional. Resultados: Se analizaron 81 casos y 162 controles. La edad más afectada en casos fue preescolar (35.8%), en controles fue edad escolar (41.4%). El sexo masculino presentó similar distribución en ambos grupos (51.8% y 51.2%). La procedencia rural fue más frecuente en los casos que en controles (58.0% versus 48.8%). Se identificaron los siguientes factores asociados a EFR: Antecedentes familiares de epilepsia (ORa 2.32, IC95%1.22­4.41, p=0.01), alteración focal en examen físico (ORa 2.23, IC95%1.10­4.55, p=0.02), neurodesarrollo anormal (ORa 2.78, IC95%1.18­6.54, p=0.02). Discusión: El control adecuado de las crisis epilépticas incide directamente en la calidad de vida y sobrevida de los pacientes. La identificación correcta de los niños con epilepsia con los factores asociados identificados en este estudio, que coinciden con lo descrito internacionalmente, permitirá hacer un mejor tamizaje y priorizar la referencia temprana a un neurólogo pediatra contribuyendo a mejorar la calidad de vida de los pacientes...(AU)

Neurocisticercosis y epilepsia en un hospital universitario de Popayán, Colombia: una serie de casos / Neurocysticercosis and epilepsy in a university hospital in Popayán, Colombia: A case series

RESUMEN INTRODUCCIÓN: La neurocisticercosis es una infección del sistema nervioso central causada por el estadio larvario del cestodo Taenia solium, y se estima que puede ocasionar hasta 30% de los casos de epilepsia en los países donde esta parasitosis es endémica. El objetivo de este estudio fue determinar la frecuencia de pacientes que presentaron epilepsia como secuela de neurocisticercosis en un hospital universitario en Popayán. MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo con todos los pacientes con diagnóstico de neurocisticercosis que ingresaron al Hospital Universitario San José entre enero 2014 y diciembre 2018 que cumplieron los criterios de inclusión. RESULTADOS: Se encontraron 50 pacientes, de estos, 40 (80%) reingresaron, encontrándose que 37 (74%) presentaron epilepsia como secuela. Las edades más afectadas fueron la de 41 a 60 años; 48 (96%) provenían del departamento del Cauca en especial de Mercaderes, y 33 (66%) de área rural. El síndrome convulsivo fue la manifestación clínica de ingreso más frecuente. La TAC fue la técnica de imagen de elección. CONCLUSIÓN: El departamento del Cauca se considera como una de las áreas endémicas para neurocisticercosis en Colombia, y la epilepsia secundaria es un secuela común.

ABSTRACT INTRODUCTION: Neurocysticercosis is an infection of the central nervous system caused by the larval stage of the cestode Taenia solium, it has been estimated to produce up to 30% of the cases in countries where this parasitosis is endemic. The objective of this study was to determine the frequency of patients who presented epilepsy as a sequel of neurocysticercosis in a university hospital in Popayán. MATERIALS AND METHODS: A retrospective study was conducted with all patients with a diagnosis of neurocysticercosis who were admitted to the Hospital Universitario San José between January 2014 and December 2018 who met the inclusion criteria. RESULTS: We found 50 patients, 40 (80%) of which were readmitted and 37 (74%) presented epilepsy as sequela. The most affected age-group was 41 to 60 years; 48 (96%) were from the department of Cauca, especially Mercaderes, and 33 (66%) from rural areas. Convulsive syndrome was the most frequent clinical manifestation on admission. CT was the imaging technique of choice. CONCLUSION: The department of Cauca is considered as an endemic area for neurocysticercosis, and secondary epilepsy was a common consequence.

Uso de cannabidiol para el control de síntomas refractarios en síndromes convulsivos y enfermedades neurodegenerativas / Use of cannabidiol for the control of refractory symptoms in convulsive syndromes and neurodegenerative diseases

Como parte de las terapias alternativas para el control de síntomas refractarios en enfermedades avanzadas destaca el uso de cannabidiol. Este se ha estudiado en patologías como enfermedad de Alzheimer, Parkinson y trastornos convulsivos. Los síndromes convulsivos están presentes en todos los grupos etarios. Dentro de este, la epilepsia es refractaria hasta en un 40 % de los pacientes, quienes han demostrado disminución en la frecuencia de convulsiones con el uso concomitante de cannabidiol y antiepilépticos convencionales, con efectos secundarios leves, como diarrea y somnolencia. Con el objetivo de determinar el uso del cannabidiol para el control de síntomas neurológicos refractarios en pacientes con síndromes convulsivos y enfermedades neurodegenerativas, se realizó una búsqueda bibliográfica en Pubmed, Scopus y Embase. Se incluyeron metaanálisis, artículos originales, revisiones sistemáticas y bibliográficas, y documentos de la Organización Panamericana de la Salud, publicados entre 2017 y 2022. Los efectos del cannabidiol lo convierten en una alternativa, adicional a la terapéutica convencional, para el control de síntomas en trastornos neurológicos, disminuyendo de forma sostenida el número total de episodios con un perfil de seguridad aceptable. Existe limitada información respecto al uso de cannabidiol en enfermedades neurodegenerativas, por lo que no se ha evidenciado su efectividad

As part of the alternative therapies for the control of refractory symptoms in advanced diseases, the use of cannabidiol stands out. It has been studied in pathologies such as Alzheimer's disease, Parkinson's disease, and convulsive disorders. Convulsive syndromes are present in all age groups. Within this group, epilepsy is refractory in up to 40 % of patients, who have shown a decrease in the frequency of seizures with the concomitant use of cannabidiol and conventional antiepileptics, with mild side effects such as diarrhea and drowsiness. To determine the use of cannabidiol for the control of refractory neurological symptoms in patients with seizure syndromes and neurodegenerative diseases, a literature search was performed in PubMed, Scopus, and Embase. Meta-analyses, original articles, systematic and literature reviews, and documents from the Pan American Health Organization, published between 2017 and 2022, were included. The effects of cannabidiol make it an alternative, in addition to conventional therapeutics, for symptom control in neurological disorders, sustainably decreasing the total number of episodes with an acceptable safety profile. There is limited information regarding the use of cannabidiol in neurodegenerative diseases, the reason its effectiveness has not been demonstrated.

Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

The utility of mobile telephone-recorded videos as adjuncts to the diagnosis of seizures and paroxysmal events in children with suspected epileptic seizures

Background. Epilepsy is often diagnosed through clinical description, but inter-observer interpretations can be diverse and misleading. Objective. To assess the utility of smartphone videos in the diagnosis of paediatric epilepsy.Methods. The literature was reviewed for evidence to support the use of smartphone videos, inclusive of advantages, ethical practice and potential disadvantages. An existing adult-based quality of video (QOV) scoring tool was adapted for use in children. A pilot study used convenience sampling of videos from 25 patients, which were reviewed to assess the viability of the adapted QOV tool against the subsequent diagnosis for the patients with videos. The referral mechanism of the videos was reviewed for the source and consent processes followed. Results. A total of 14 studies were identified. Methodologies varied; only three focused on videos of children, and QOV was formally scored in three. Studies found that smartphone videos of good quality assisted the differentiation of epilepsy from non-epileptic events, especially with accompanying history and with more experienced clinicians. The ethics and risks of circulation of smartphone videos were briefly considered in a minority of the reports. The pilot study found that the adapted QOV tool correlated with videos of moderate and high quality and subsequent diagnostic closure.Conclusions. Data relating to the role of smartphone video of events in children is lacking, especially from low- and middle-income settings. Guidelines for caregivers to acquire good-quality videos are not part of routine practice. The ethical implications of transfer of sensitive material have not been adequately addressed for this group. Prospective multicentre studies are needed to formally assess the viability of the adapted QOV tool for paediatric videos.

Childhood seizures: assessment of the knowledge, attitude and home interventions among patients attending a paediatric outpatient clinic in Nigeria

Most seizures in children occur outside the hospital and effective first aid would protect individuals from harm. Study assessed the knowledge, attitude and home-based interventions for childhood seizures.Methodology: This was a descriptive cross-sectional survey conducted from 1stJune to 31stDecember, 2021 among caregivers of patients in a Paediatric outpatient clinic. Interviewer-administered questionnaires were used to assess knowledge, attitude, and home intervention of childhood seizures. Data were analyzed using SPSS 24 and results presented as frequency tables, percentages and charts. P-values < 0.05 were considered significant.Results: Out of 218 respondents, the commonest source of information on childhood seizures was from friends and relatives 126(73.2%). Fever was the commonest known cause. Only 15(6.9%) recognized seizure as a neurological disorder. Jerking of the body and clenchingof the teeth were the commonest recognizable symptoms. The majority said seizures were contagious (176(80.7%) and children with seizures should not go to school 187(85.8%). The overall knowledge score was poor. Negative attitudes included avoidance 19(8.7%), isolation from playing with peers (15(6.9%) and from the public 17(7.8%). Common interventions during seizures were putting palm kernel oil in the mouth while only 25(29.4%) took the child to the hospital or laid him down away from harmful objects 25(29.4%). The practice of home intervention for seizures was good in only 11(5.0%) of respondents

Epilepsy classification (ILAE Classification 2017) in resource-limited countries: A cross-sectional study on epilepsy in pediatric patients from Sudan

Background: The objective of this study is to utilize the ILAE 2017 to classify epilepsy patients and determine its applicability in Sudan. Methods: This study is a prospective, descriptive, cross-sectional research conducted in two pediatric epilepsy clinics in Khartoum State, Sudan. Results: In this cross-sectional study, 350 pediatric patients with epilepsy were included, with a mean age of 8.4 ± 4.7 years and a mean illness duration of 4.71 ± 3.91 years. The ILAE classification was applied, showing that 71.11% of patients had generalized onset seizures, 27.7% had focal onset seizures, and only 1.1% had unknown onset seizures. Among patients with focal onset seizures, 56.4% had intact awareness, while 43.6% had impaired levels of awareness. The majority of patients who had generalized onset seizures experienced motor onset seizures, with tonicclonic seizures being the most common (44.2%). Nearly all patients with unknown onset seizures experienced tonic-clonic convulsions. These findings provide insights into the prevalence and types of seizures among pediatric epilepsy patients in Sudan and can guide clinicians in developing appropriate treatment plans. Conclusion: This study highlights the importance of utilizing the latest ILAE classification 2017 in epilepsy classification and its potential utilization in resource limited areas like Sudan.

Construction of an epileptic seizure prediction model using a semi-supervised method of generative adversarial and long short term memory network combined with Stockwell transform / 南方医科大学学报

OBJECTIVE@#To propose a semi-supervised epileptic seizure prediction model (ST-WGAN-GP-Bi-LSTM) to enhance the prediction performance by improving time-frequency analysis of electroencephalogram (EEG) signals, enhancing the stability of the unsupervised feature learning model and improving the design of back-end classifier.@*METHODS@#Stockwell transform (ST) of the epileptic EEG signals was performed to locate the time-frequency information by adaptive adjustment of the resolution and retaining the absolute phase to obtain the time-frequency inputs. When there was no overlap between the generated data distribution and the real EEG data distribution, to avoid failure of feature learning due to a constant JS divergence, Wasserstein GAN was used as a feature learning model, and the cost function based on EM distance and gradient penalty strategy was adopted to constrain the unsupervised training process to allow the generation of a high-order feature extractor. A temporal prediction model was finally constructed based on a bi-directional long short term memory network (Bi-LSTM), and the classification performance was improved by obtaining the temporal correlation between high-order time-frequency features. The CHB-MIT scalp EEG dataset was used to validate the proposed patient-specific seizure prediction method.@*RESULTS@#The AUC, sensitivity, and specificity of the proposed method reached 90.40%, 83.62%, and 86.69%, respectively. Compared with the existing semi-supervised methods, the propose method improved the original performance by 17.77%, 15.41%, and 53.66%. The performance of this method was comparable to that of a supervised prediction model based on CNN.@*CONCLUSION@#The utilization of ST, WGAN-GP, and Bi-LSTM effectively improves the prediction performance of the semi-supervised deep learning model, which can be used for optimization of unsupervised feature extraction in epileptic seizure prediction.

Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model / Ratas sem Status Epilepticus apresentam comportamento do tipo crise epiléptica na fase crônica do modelo experimental da Pilocarpina

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.

Severe headache, seizures and supraventricular tachycardia in a 33-year-old Filipino male with confirmed COVID-19: A case report

@#COVID-19 primarily presents as a pulmonary problem, ranging from mild respiratory illness to fatal acute respiratory distress syndrome. Most common manifestations are fever (89%) and cough (72%), while headache and arrhythmia are found in 28% and 17%, respectively. We aim to present a confirmed COVID-19 case presenting with both neurologic and cardiac manifestations. A 33-year-old Filipino male nurse initially consulted at the emergency room due to progressive diffuse headache, with associated localized seizures progressing to generalized tonic clonic seizure and arrhythmia. He had no coryza, cough, sore throat, and diarrhea. He was previously well and had no known co-morbidities or direct exposure to confirmed COVID-19 patients. Physical examination showed elevated blood pressure, tachycardia, and sensory and motor deficits in the left upper and lower extremities. Pertinent diagnostic test results included the detection of SARS-CoV-2 viral RNA via RT-PCR. Imaging studies demonstrated cortical venous thrombosis with hemorrhagic venous infarction in the right parietal lobe. Ground glass appearance on the middle lobe of the left lung was also evident. ECG showed supraventricular tachycardia. Prothrombin time, activated partial thromboplastin time, and D-dimer were all within the normal limits. Carotid massage was done. He was treated with anti-epileptics, anticoagulants, antiarrhythmics, antivirals, antibiotics, and supportive management. During the hospital stay, his symptoms resolved; he was discharged after 21 days. Follow-up done after 3 weeks revealed no recurrence of severe headache, seizure, or tachycardia. It is theorized that an interplay exists between ACE-2 tropism, systemic inflammation, cytokine storm, and hypoxemia in the background of COVID-19 infection. These mechanisms may lead to thrombosis and arrhythmia resulting to neurologic derangements and myocardial injury. Underlying mechanisms make the cerebro-cardiovascular systems vulnerable to the coronavirus disease 2019 infection. COVID-19 should therefore be part of the differential diagnoses in patients presenting with headache, seizures, and arrhythmias.

Eficácia e segurança do Felbamato comparado a medicamentos disponíveis no SUS para o tratamento da epilepsia refratária em crianças e adultos: revisão rápida de evidências / Effectiveness and safety of Felbamate compared to drugs available in SUS for the treatment of refractory epilepsy in children and adults: rapid evidence review

Tecnologia: Felbamato. Indicação: Tratamento de epilepsia refratária. Pergunta: O Felbamato é mais eficaz e seguro comparado a anticonvulsivantes disponíveis no Sistema Único de Saúde (SUS) em pacientes com epilepsia refratária? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas 2 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: O felbamato não demonstrou ser uma opção mais benéfica que os demais medicamentos disponíveis no SUS no tratamento de epilepsia refratária a medicamentos. Salienta-se que a maior parte das evidências eram de baixa certeza

Technology: Felbamate. Indication: Treatment of refractory epilepsy. Question: Is felbamate more effective and safer compared to anticonvulsants available in Brazilian Public Health System in patients with refractory epilepsy? Methods: A rapid review of evidence (overview) of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Two systematic reviews that met the inclusion criteria were selected. Conclusion: Felbamate did not prove to be a more beneficial option than the other drugs available in the Brazilian Public Health System in the treatment of drug-refractory epilepsy. It should be noted that most of the evidence was of low certainty

Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice / Efeitos anticonvulsivantes da desvenlafaxina na modulação da monoamina cerebral e do estresse oxidativo em camundongos

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P < 0,01) e o LPO reduziu significativamente (P < 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.

Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy / 中华儿科杂志

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

Factors influencing the efficacy of initial adrenocorticotropic hormone therapy for infantile epileptic spasms syndrome / 中国当代儿科杂志

OBJECTIVES@#To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis.@*METHODS@#The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis.@*RESULTS@#ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05).@*CONCLUSIONS@#Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.

Genetic analysis of a case of mild epilepsy due to variant of SCN9A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a patient with epilepsy and provide genetic counseling.@*METHODS@#A patient who had visited the Center for Reproductive Medicine of Shandong University on November 11, 2020 was selected as the study subject, and her clinic information was collected. Candidate variant was identified through whole exome sequencing (WES), and Sanger sequencing was used for validation. Possible transcriptional changes caused by the variant was detected by reverse transcription-PCR and Sanger sequencing.@*RESULTS@#The patient was a 35-year-old female with no fever at the onset, loss of consciousness and abnormal firing in the temporal lobe, manifesting predominantly as convulsions and fainting. WES revealed that she had harbored a heterozygous c.2841+5G>A variant of the SCN9A gene, which was verified by Sanger sequencing. cDNA sequencing confirmed that 154 bases were inserted between exons 16 and 17 of the SCN9A gene, which probably produced a truncated protein and affected the normal function of the SCN9A protein. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.2841+5G>A variant was classified as likely pathogenic (PVS1_Strong+PM2_Supporting).@*CONCLUSION@#The c.2841+5G>A variant of the SCN9A gene probably underlay the epilepsy in this patient. Above finding has enriched the variant spectrum of the SCN9A gene and provided a basis for the prenatal diagnosis and preimplantation genetic testing for this patient.

Analysis of OTC gene variants in four children with delayed onset Ornithine transcarbamylase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical manifestation and genetic basis for four children with delayed onset Ornithine transcarbamylase deficiency (OTCD).@*METHODS@#Clinical data of four children with OTCD admitted to the Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted.@*RESULTS@#The clinical manifestations of the four children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c.421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c.119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c.607T>A (p.S203T) variant in exon 5 of the OTC gene. Among these, the c.607T>A variant was unreported previously and predicted to be pathogenic (PM1+PM2_Supporting+PP3+PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers.@*CONCLUSION@#The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c.607T>A variant has enriched the mutational spectrum of the OTC gene.

Acupuncture for prevention of moderate to severe seasonal allergic rhinitis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of acupuncture for prevention of moderate to severe seasonal allergic rhinitis.@*METHODS@#A total of 105 patients with moderate to severe seasonal allergic rhinitis were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (52 cases, 4 cases dropped off). The patients in the observation group were treated with acupuncture at Yintang (GV 24+), Yingxiang (LI 20), Hegu (LI 4), Zusanli (ST 36), Fengchi (GB 20), Feishu (BL 13), etc. 4 weeks before the seizure period, once every other day, 3 times a week for 4 weeks. The patients in the control group were not given any intervention before the seizure period. Emergency drugs can be given appropriately during the seizure period in both groups. After seizure period, the seizure rate was recorded in the two groups; before treatment and on week 1, 2, 4, 6 of seizure period after treatment, the rhinoconjunctivitis quality of life questionnaire (RQLQ) score and total nasal symptom score (TNSS) were observed in the two groups; the rescue medication score (RMS) was recorded on week 1-6 of seizure period in the two groups.@*RESULTS@#The seizure rate of the observation group was 84.0% (42/50), which was lower than 100.0% (48/48) in the control group (P<0.05). After treatment, the scores of RQLQ and TNSS at each time point of seizure period were decreased compared with before treatment in the observation group (P<0.01), which were lower than the control group (P<0.01). The RMS score at each time point of seizure period in the observation group was lower than the control group (P<0.05, P<0.01).@*CONCLUSION@#Acupuncture can reduce the incidence of moderate to severe seasonal allergic rhinitis, relieve the symptoms, improve the quality of life and reduce the use of emergency drugs.

Clinical features of children with febrile seizures caused by Omicron variant infection / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with febrile seizures after Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups.@*RESULTS@#There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05).@*CONCLUSIONS@#Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.