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Epilepsy's cyclic nature, increasingly quantified through advancements in continuous electroencephalography (cEEG), reveals robust seizure cycles including circadian, multidien, and circannual rhythms. Understanding these cycles' mechanisms and clinical implications, such as seizure forecasting and optimized treatment timing, is crucial. Despite historical observations, detailed analysis of seizure timing cycles has become feasible only recently, necessitating further research to confirm generalizability and clinical relevance. This paper reviews current literature on circadian rhythms in epilepsy, focusing on temporal seizure patterns and identifying knowledge gaps. A comprehensive review of studies, primarily using PubMed, synthesizes key findings from 20 studies on the temporal dynamics of epileptic activity. Research shows consistent circadian rhythms in seizure activity, with distinct daily peaks. Seizures often follow daily patterns, termed "seizure rush hours," with specific seizure types linked to particular times and influenced by sleep-wake cycles. These findings underscore the importance of understanding temporal patterns in epilepsy. Understanding these rhythms can enhance seizure prediction, diagnosis, and personalized treatment strategies. The significant role of biological rhythms suggests that tailored treatments based on individual circadian profiles could improve patient outcomes and quality of life. Further research is essential to elucidate the mechanisms driving these influences and validate findings across diverse cohorts.
A natureza cíclica da epilepsia, cada vez mais quantificada por meio dos avanços na eletroencefalografia contínua (cEEG), revela ciclos de crises epilépticas (CE) robustos, incluindo ritmos circadianos, multidiários e circanuais. Compreender os mecanismos e as implicações clínicas desses ciclos, como a previsão de CE e a otimização do momento do tratamento, é crucial. Apesar das observações históricas, a análise detalhada dos ciclos de tempo das CE tornou-se viável apenas recentemente, exigindo mais pesquisas para confirmar a generalização e a relevância clínica. Este artigo revisa a literatura atual sobre ritmos circadianos na epilepsia, focando nos padrões temporais das CE e identificando lacunas no conhecimento. Uma revisão abrangente dos estudos, principalmente utilizando o PubMed, sintetiza os principais achados de 20 estudos sobre a dinâmica temporal da atividade epiléptica. A pesquisa mostra ritmos circadianos consistentes na atividade das CE, com picos diários distintos. As CE frequentemente seguem padrões diários, denominados "horários de pico das convulsões" ("seizure rush hours"), com tipos específicos de CE vinculados a determinados horários e influenciados pelos ciclos sono-vigília. Esses achados destacam a importância de entender os padrões temporais na epilepsia. Compreender esses ritmos pode melhorar a previsão, o diagnóstico e as estratégias de tratamento personalizado das CE. O papel significativo dos ritmos biológicos sugere que tratamentos personalizados com base nos perfis circadianos individuais podem melhorar os resultados e a qualidade de vida dos pacientes. Mais pesquisas são essenciais para elucidar os mecanismos que impulsionam essas influências e validar os achados em diversas coortes.
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Objective:To summarize the clinical characteristics of patients with epilepsy caused by focal cortical dysplasia (FCD), and identify the influencing factors for postoperative seizure controls.Methods:Fifty-seven patients with epilepsy caused by FCD admitted to Department of Neurosurgery, Third Affiliated Hospital of Zhengzhou University from July 2019 to November 2023 were chosen; standard preoperative evaluation, surgery, postoperative management and follow-up were performed. A retrospective study of clinical data, imaging and video electroencephalogram (VEEG) data, surgical approaches, pathological findings, and follow-up data was performed; influencing factors for postoperative seizure controls were analyzed.Results:In these 57 patients with epilepsy caused by FCD, 29 were males (50.88%) and 28 were females (49.12%). Onset age was 30.00 (8.00, 74.50) months, and surgery age was 95.00 (50.00, 138.50) months. Focal to bilateral tonic-clonic seizures (42/57; 73.68%) and epileptic spasms (13/57; 22.81%) were common seizure types. Cranial MRI was positive in 34 patients (59.65%), mainly manifested as abnormal cortical gyri/sulci morphology (17/57; 29.82%). In 43 patients accepted PET-CT, hypometabolic sites were detected in 40 (93.02%), and complete agreement between PET/MRI fusion results and actual lesion sites was noted in 40 (93.02%). FCD type I was noted in 16 patients (28.07%), type II in 39 (68.42%), and type III in 2 (3.51%). By December 2023, 44 (77.19%) had Engel grading I, 4 (7.02%) had grading II, 4 (7.02%) had grading III, and 5 (8.77%) had grading IV. Children with good prognosis (Engel grading I+II) and those with poor prognosis (Engel grading III+IV) showed significant differences in terms of time from first seizure to surgery, positive/negative MRI, and regularity of postoperative ASMs ( P<0.05). Conclusions:Focal to bilateral tonic-clonic seizure is the most common seizure type in patients with epilepsy caused by FCD, and abnormal cortical gyri/sulci morphology is the most common MRI manifestation; PET/MRI fusion imaging is superior to PET-CT or MRI in identifying epileptogenic foci. Poor seizure control can be noted in patients with long onset time to surgery, with negative cranial MRI results, or with irregular postoperative ASMs.
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Epilepsy is a kind of brain dysfunction syndrome characterized by paroxysmal,transient,repetitive and rigid characteristics caused by abnormal discharge of highly synchronized neurons in the brain.Epilepsy is often accompanied by cognitive dysfunction.At present,anti-seizure medications are the most important methods of clinical treatment.Most of the traditional anti-seizure medications can cause cognitive dysfunction,and the influence of new anti-seizure medications on cognitive function is not completely clear.This paper reviews the influence of new anti-seizure medications on cognitive function and the possible related mechanisms of action based on relevant literature at home and abroad.It is expected that clinicians should pay attention to cognitive function in the process of diagnosis and treatment of epilepsy,and help clinicians realize the influence of anti-seizure medications on cognitive function,and rationally choose anti-seizure medications for patients.
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Epilepsy is an episodic, transient, stereotypic brain dysfunction caused by highly synchronized abnormal neuronal discharges in the brain, with unpredictable timing of seizures, for which the main treatment modalities are antiepileptic drugs and surgery. Its diagnosis and treatment require a large number of aids and clinical experience. For multiple clinical aspects of epilepsy, such as seizure prediction, drug therapy prognosis, and surgical treatment evaluation, machine learning can incorporate multiple clinical and imaging factors through deep mining of data, establish corresponding learning models, improve the efficiency and accuracy of epilepsy diagnosis, realize individualized application of antiepileptic drugs, and improve the preoperative evaluation and prognosis of epilepsy patients.
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Objective:To investigate and analyze the use and duration of anti-seizure medications (ASMs) in patients with chronic epilepsy after autoimmune encephalitis (AE), as well as the effect of ASMs use on the formation of this epilepsy to provide relevant evidence for the choice of ASMs in patients with acute seizure or chronic epilepsy after AE.Methods:A retrospective follow-up study was performed on AE patients (including patients with antibody-negative autoimmune limbic encephalitis) diagnosed in the Affiliated Brain Hospital of Nanjing Medical University from December 1, 2013 to October 31, 2022. The dates of the first seizure onset and the chronic epilepsy formation (defined as 1 year after immunotherapy) were recorded. The initial time, types and numbers of ASMs used in acute symptomatic seizure (ASS) and the maintenance time, types and numbers of ASMs in chronic epilepsy period (the continuation or the combined therapy of ASMs) were collected, respectively. A Logistic regression model was used to analyze multi-influencing factors on the formation of chronic epilepsy after AE.Results:A total of 332 patients were enrolled in this study, of whom 32.5% (108/332) with antibody-negative autoimmune limbic encephalitis. In total, 54.8% (182/332) of patients were males, and the age of onset was (40.7±19.7) years. Finally, 81.0% (269/332) of participants manifested ASS, and 57.2% (190/332) developed chronic epilepsy up to the last follow-up. The follow-up time was 1-8 years, with a median of 2 years. All patients received ASMs treatment during ASS period. Among the ASS patients, 48.0% (129/269) were prescribed monotherapy of ASMs, and 52.0% (140/269) were given the combined therapy of ASMs. Of all the patients with ASMs, 70.3% (189/269) were given early ASMs treatment (within 24 hours of the seizure onset), and 29.7% (80/269) were given delayed ASMs treatment. Subsequently, 81.0% (218/269) of the ASS patients continued the ASMs treatment (>6 months), and 19.0% (51/269) stopped use of ASMs. In the chronic epilepsy stage, 79.5% (151/190) of thee epilepsy patients continued ASMs, of whom 37.1% (56/151) were treated with monotherapy, and 62.9% (95/151) were treated with combined therapy. The incidence of chronic epilepsy was 81.3% (65/80) in the delayed ASMs treatment group, higher than the 66.1% (125/189) in the early ASMs treatment group,with statistically significant difference (χ 2=6.189, P=0.013). There were no statistically significant differences in the ASMs types and whether combined therapy of ASMs was used between chronic epilepsy group and non-chronic epilepsy group. The Logistic regression model showed that delayed ASMs treatment ( OR=2.306,95% CI 1.032-6.387, P=0.018), positive anti-neuronal intracellular antibodies ( OR=2.626,95% CI 1.536-9.531, P=0.004,compared with anti- neuronal surface antibodies), abnormal brain magnetic resonance imaging ( OR=9.883,95% CI 3.608-27.071, P<0.001), elevated cerebrospinal fluid protein ( OR=2.874,95% CI 1.115-7.409, P=0.029), and abnormal electroencephalogram ( OR=9.287,95% CI 3.767-22.896, P<0.001) were independent risk factors for chronic epilepsy after AE. Conclusions:The development of chronic epilepsy after AE is associated with the occurrence of ASS and the delayed use of ASMs, but the type of ASMs or whether the combined ASMs therapy is used is not associated with the formation of chronic epilepsy after AE. It is concluded that early ASMs treatment for the AE patients with ASS may reduce the incidence of chronic epilepsy. For AE patients with ASS who have undergone early standardized treatment, long-term, combined ASMs treatment may not be necessary.
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Objectives@#To perform a pilot study on the frequency of sleep-disturbance (Total sleep Disturbance Score (TSD) of > 41) in children diagnosed with Drug Resistant Epilepsy aged 4 to 12 years, using the Children’s Sleep Habits Questionnaire (CSHQ).@*Methodology@#The Children’s Sleep Habits Questionnaire (CSHQ) was used to screen for sleep disturbances among 73 patients aged 4 to 12 years old with drug-resistant epilepsy seen at the Seizure Clinic of Philippine Children’s Medical Center. Descriptive statistics were used to characterize sociodemographic variables, and sleep and epilepsy-related variables. Continuous data were presented as mean ± standard deviation (SD), and categorical data as frequencies (percentages).@*Results@#Sleep disturbances were common and severe in children with drug-resistant epilepsy. Out of the seventy-three participants, 61 patients had a TSD score of greater than 41 (84%) and 12 (16%) had TSD scores below 41 with a mean CSHQ score of 58. The most frequently occurring sleep disturbances involve the domains of bedtime resistance (29%), night wakings (28%), and daytime sleepiness (23%). Meanwhile, the least frequently occurring sleep disturbances involve the domains of sleep disordered breathing (76%), parasomnias (65%), and sleep anxiety (56%).@*Conclusion@#Majority of the children with drug-resistant epilepsy are sleep disturbed exhibiting high TSD scores (>41) using the Children’s Sleep Habits Questionnaire. We recommend to actively evaluate and screen for sleep and behavioral problems concurrently in children with epilepsy.
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Epilepsia , PediatriaRESUMO
SUMMARY OBJECTIVE: The aim of this study was to evaluate the association between nutritional status, inflammation, and susceptibility to seizures in febrile children. METHODS: This observational single-center study was carried out from January 2020 to December 2023 with 324 children aged 6 months and 6 years; 106 were diagnosed with febrile seizure, 108 were febrile children, and 110 were healthy controls. The prognostic nutritional index and neutrophil-to-lymphocyte ratio were calculated, and the cutoff threshold was established through receiver operating characteristics. The study utilized correlation and univariate-multivariate logistic regression analysis. The comparison between simple and complex febrile seizure was conducted to analyze differences. RESULTS: The optimal cutoff values were identified as 61.25 for prognostic nutritional index and 1.04 for neutrophil-to-lymphocyte ratio. Our findings showed a significant negative association between febrile seizure and platelet count, high C-reactive protein, and high ferritin levels. Additionally, the febrile seizure group showed a significant positive correlation with high neutrophil-to-lymphocyte ratio values (≥1.04) and body temperature (≥38). Our findings revealed that high neutrophil-to-lymphocyte ratio, high C-reactive protein, and age less than 18 months were independently associated with seizure susceptibility in febrile children. CONCLUSION: High neutrophil-to-lymphocyte ratio values and low prognostic nutritional index scores may serve as novel surrogate independent factors for seizure susceptibility in febrile children. Febrile children who are less than 18 months old are more prone to experience seizures than older febrile children. Moreover, there was a correlation between febrile seizures and elevated C-reactive protein levels and neutrophil-to-lymphocyte ratio values.
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The International League Against Epilepsy (ILAE) task force on neonatal seizures has recently published draft guidelines and consensusbased recommendations on the treatment of neonatal seizures. This update provides a summary of the recommendations and the changes in management compared to the previous WHO ILAE guidelines, published in 2011, with emphasis on practical decision making requirements for a pediatrician.
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Background:Benzodiazepines are the first-line anti-seizure medication (ASM) for generalized convulsive status epilepticus (GCSE), but they fail to end seizures in a third of cases. Combining benzodiazepines with another ASM that acts by a different pathway could be a potential strategy for rapid control of GCSE. Objectives: To evaluate the efficacy of adding levetiracetam to midazolam in the initial treatment of pediatric GCSE. Design: Double-blind randomized controlled trial. Setting: Pediatric emergency room at Sohag University Hospital between June, 2021 and August, 2022. Participants: Children aged between 1 month and 16 years with GCSE lasting more than 5 min. Interventions: Intravenous levetiracetam (60 mg/kg over 5 min) and midazolam (Lev-Mid group) or placebo and midazolam (PlaMid group) as first-line anticonvulsive therapy. Outcome measures: Primary: cessation of clinical seizures at 20- min study time point. Secondary: cessation of clinical seizures at 40-min study time point, need for a second midazolam dose, seizure control at 24-hr, need for intubation, and adverse effects. Results: Cessation of clinical seizures at 20-min occurred in 55 children (76%) in Lev-Mid group compared with 50 (69%) in the PlaMid group [RR (95% CI) 1.1 (0.9-1.34); P=0.35]. No significant difference was found between the two groups regarding the need for a second midazolam dose [44.4% vs 55.6%; RR (95% CI) 0.8 (0.58- 1.11); P=0.18] as well as cessation of clinical seizures at 40-min [96% vs 92%; RR (95% CI)1.05 (0.96-1.14); P=0.49] and seizure control at 24-hr [85% vs 76%; RR (95% CI) 1.12 (0.94-1.3); P=0.21]. Intubation was required for three patients in the Lev-Mid group and six patients in the Pla-Mid group [RR (95%CI) 0.5 (0.13- 1.92); P=0.49]. No other adverse effects or mortality were observed during the 24-hour study timeframe. Conclusion: Combined levetiracetam and midazolam for initial management of pediatric GCSE presents no significant advantage over midazolam alone in cessation of clinical seizures at 20-min.
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Objective: To assess proportion and predictors of lesion calcification in children aged 2-12 years with neurocysticercosis at six months follow up. Method: Children aged between 2 and 12 years with Neurocysticercosis diagnosed on MRI brain were initially included and followed up for 6 months. Repeat CECT brain at 6 months was done to find if the lesion persisted/calcified/ resolved. Results: 16 out of 30 patients (53.3%) had calcification at six months follow up. Perilesional edema at the initial stage of the presentation was significantly associated with calcification at 6 months (P=0.042). Conclusion: Perilesional edema at the time of presentation was significantly associated with calcification in children with neurocysticercosis, six months after diagnosis.
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Background: Epilepsy is an abnormal excessive electric neuronal activity and always represents by recurrent seizures. There is positive feedback cycle between epileptogenesis and brain inflammation. It has been proved that an inflammatory enzyme, cyclooxygenase (COX) (especially isoform-2, a constitutive enzyme), expressed in some important parts of the central nervous system and is responsible to induced inflammation locally and having seizurogenic property. Aim and Objective: The goal of this study was to see if celecoxib (a selective COX-2 inhibitor) could reduce the maximal electroshock seizure (MES)-induced seizures in mice. Materials and Methods: Celecoxib injected intraperitoneally in two different doses 5 mg/kgb/w and 10 mg/kg b/w, in albino Swiss mice and in two different phases. MES was elicited and length of different phases was noted. Length of tonic hindlimb extension was considered as indicator of anti-epileptic activity. Results: Celecoxib, when given intraperitoneally, exert significant reduction in the duration of THLE. This action of celecoxib strongly suggests the involvement of inflammation in the pathophysiology of epilepsy. Conclusion: The findings are suggestive of the therapeutic significance of celecoxib, as a future antiepileptic agent for seizure management.
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ABSTRACT Epilepsy is a multifactorial pathology that has allowed the development of various drugs aiming to combat it. This effort was formally initiated in the 1940s when phenytoin began to be used. It eventually turned out to be a drug with great anticonvulsant efficacy. At present, several potentially good new generation anti-seizure medications (ASMs) have been developed. Most of them present more tolerability and less toxic effects. However, they continue to have adverse effects at different levels. In addition, some seizures are difficult to treat with ASMs, representing 30% of the total cases of people who suffer from epilepsy. This review aims to explore the genetic and molecular mechanisms of ASMs neurotoxicity, proposing the study of damage caused by epileptic seizures, in addition to the deterioration generated by anti-seizure drug administration within the central nervous system. It is beyond question that there is a need to develop drugs that lower the lower the risk of secondary and toxic effects of ASMs. Simultaneously, we must find strategies that produce fewer harmful interactions and more health benefits when taking anti-seizure drugs.
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Resumen: Introducción: las crisis convulsivas pueden desencadenar fracturas y luxaciones. Las lesiones dependen de la severidad, duración y el tipo de crisis. Presentamos un caso clínico de un varón que presentó una fractura luxación central bilateral de cadera tras episodio de crisis convulsiva. Un caso pocas veces descrito en la literatura con un manejo complejo y poco habitual. Caso clínico: paciente de 77 años con antecedentes de deterioro cognitivo moderado que sufrió una luxación bilateral central de cadera en contexto de una crisis convulsiva generalizada. Clínicamente, a su llegada a urgencias, el paciente presentaba un acortamiento de la extremidad inferior derecha en comparación con la contralateral, rotación externa y bloqueo articular a la realización del log roll test en ambas extremidades. Se realizó estudio de imagen y optimización clínica previo a cirugía. Se realizó en dos tiempos: primero la cadera izquierda al octavo día de ingreso y la cadera derecha al decimoquinto. En ambas cirugías se realizó el mismo procedimiento mediante implantación de anillo antiprotrusivo y prótesis con cotilo de doble movilidad con vástago femoral no cementado. En el postoperatorio inmediato, el paciente no presentó ninguna complicación asociada a la cirugía. En el seguimiento a los 12 meses, el paciente realiza carga completa con un Harris hip score (HHS) de 77 cadera derecha y 79 en la izquierda; 12 puntos en la escala WOMAC. No ha presentado complicaciones postoperatorias hasta el momento. Conclusiones: estas lesiones son poco comunes en nuestra práctica diaria, donde disponemos de múltiples opciones para abordarlas. En nuestro paciente, el empleo de la artroplastía y de anillos antiprotrusivos nos ofrecen ventajas respecto a las técnicas de síntesis de la fractura, como una movilización precoz y evitar desarrollo prematuro de una artrosis postraumática, con resultados buenos, funcionales y pocas complicaciones postoperatorias.
Abstract: Introduction: seizures can trigger fractures and dislocations. Injuries depend on the severity, duration and type of seizure. We present a case report of a male patient who presented with a bilateral central dislocation fracture of the hip following an episode of seizure. A case rarely described in the literature with complex and unusual management. Case report: a 77-year-old man with a history of moderate cognitive impairment suffered a bilateral central dislocation of the hip in the context of a generalized epileptic seizure. Clinically on arrival at the emergency department, the patient presented shortening of the right lower extremity compared to the contralateral, external rotation and joint locking on log roll test in both extremities. An imaging study and clinical optimization were performed prior to surgery. It was performed in two stages. First the left hip on the 8th day of admission, and the right hip on the 15th. In both surgeries the same procedure was performed, with implantation of an antiprotrusive ring and a double mobility cup prosthesis with an uncemented femoral stem. In the immediate postoperative period, the patient did not present any complications associated with the surgery. At 24-month follow-up, the patient performed full weight bearing with a Harris hip score (HHS) of 77 on the right hip and 79 on the left; 12 points on the WOMAC scale. No postoperative complications have occurred so far. Conclusions: these injuries are uncommon in our daily practice, where multiple options are available to address them. In our patient, the use of arthroplasty and antiprotrusive rings offers advantages over fracture synthesis techniques, such as early mobilization with moderate functional results and few postoperative complications.
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Objectives: To evaluate the AIIMS Modified INCLEN tool for the diagnosis of epilepsy. Methods: This cross-sectional study enrolled 250 children aged 1 month to 18 years presenting with complaints of abnormal body movements to either the pediatric or neurology outpatient departments in our institution between October 1, 2018 and June 30, 2020. The All India Institute of Medical Sciences (AIIMS) modified International Clinical Epidemiology Network (INCLEN) diagnostic tool for epilepsy (AIIMS modified INDT-EPI) was administered and a diagnosis was made, which was further verified by a pediatrician or a neurologist. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: The study tool had a sensitivity of 87.6% and specificity of 84.0%. The PPV and NPV of the study tool were 86.8% and 84.9%, respectively. Conclusion: The study tool has good psychometric properties for physician assessment with regard to diagnosis of epilepsy.
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Objective:To illustrate the onset of epileptic seizures in children with brain injury admitted in pediatric intensive care unit (PICU), and to explore the risk factors and the correlation between epileptic seizures and the prognosis.Methods:Clinical data of pediatric patients with brain injury who were admitted to PICU of Peking University First Hospital from January 2013 to December 2019, and monitored by video electroencephalography (VEEG) were retrospectively collected, including general demographic information, etiological data, clinical seizures prior to VEEG performing, in-hospital mortality, brain function score, VEEG manifestations, etc.Seizures detected by VEEG were the primary outcome, and prognosis when discharged from PICU was the secondary outcome. Logistic regression was used to analyze the factors associated with seizures and poor outcome. Results:A total of 284 children were included, involving 54.9%(156/284) males.The median age of included children was 1.7(0.5, 5.0) years.Stratified by the cause of disease, 45.1%(128/284) had epilepsy, 26.1%(74/128) had genetic metabolic disease, and 14.4%(41/284) had central nervous system infection.A total of 82.0%(233/284) children had abnormal VEEG background activities, and 59.5%(169/284) had interictal epileptic discharges.Seizures were detected in 106 cases, including 39.6%(42/106) of non-convulsive seizures and 24.5%(26/106) of non-convulsive epileptic states.There were 12.0% (34/284) had poor prognosis at discharge, including 24 patients died in-hospital, and Pediatric Cerebral Performance Category scores were increased in 10 survivors.Multivariate Logistic regression analysis showed that seizures existed before VEEG monitoring and interictal epileptiform discharge were the independent risk factors for seizure.Besides, mental retardation, sepsis related encephalopathy, consciousness abnormality during VEEG, abnormal VEEG background activity, and epileptic status were significantly correlated with the poor prognosis of children with brain injury in PICU. Conclusions:The incidence of electrographic seizure is higher in children with brain injury in PICU, and VEEG monitoring is beneficial to children with brain injury that achieves an early identification of seizures and prediction of prognosis.
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Objective:To investigate the risk factors of recurrence of febrile seizures within 24 hours, so as to provide clinical evidence for early identification of children with risk factors and taking interventions.Methods:A total of 384 children with febrile seizures admitted to the Department of Pediatrics at Hebei General Hospital from June 2019 to June 2021 were selected as the study subjects, and were divided into single seizure group and recurrent seizures group.The clinical data of two groups and the risk factors of recurrent seizures were analyzed retrospectively.Results:A total of 384 children, aging from six months to five years, were diagnosed with febrile seizures.There were 296 cases in the single seizure group and 88 cases in the recurrent seizures group.First seizure, the age of the first sezures, temperature, duration of seizure ≥15 minutes, positive family history and C-reactive protein levels showed statistically significant differences between two groups(all P<0.05). Logistic regression analysis showed that non-first seizure( OR=2.085, 95% CI 1.232-3.529, P=0.006), the age of first seizure( OR=0.970, 95% CI 0.948-0.993, P=0.010), duration of seizure ≥15 minutes( OR=3.587, 95% CI 1.497-8.596, P=0.004) and positive family history( OR=1.892, 95% CI 1.126-3.180, P=0.016) were risk factors of recurrence of febrile seizures within 24 hours.The ROC curve analysis showed that the combination of four risk factors had a higher predictive value, and the area under curve was 0.974. Conclusion:Non-first seizure, the age of first seizure, cluration of seizure ≥15 minutes and positive family history are the risk factors of recurrence of febrile seizures within 24 hours.Children with four risk factors are more likely to have recurrent seizure, and could be used as an indicator for individualized prediction.
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Objective:To study the neurodevelopmental prognosis and risk factors for adverse outcomes of neonatal seizure.Methods:From December 2019 to November 2020, infants with neonatal seizure diagnosed in our hospital were enrolled in this retrospective study. Based on survival or not, mental development index (MDI), psychomotor development index (PDI) and seizure episodes at the age of 12 months, the infants were assigned into adverse outcome group and normal outcome group. The risk factors for adverse outcomes were statistically analyzed.Results:A total of 75 infants were enrolled,including 39 cases in adverse outcome group and 36 in normal outcome group. 69 cases showed abnormal amplitude-integrated electroencephalogram(aEEG), including 38 mildly abnormal cases,23 moderately abnormal cases and 8 severely abnormal cases, The incidences of adverse outcomes and mortality rates were significantly different ( P<0.05) among infants with different severity levels of aEEG abnormalities and the severity levels of aEEG abnormalities were positively correlated with adverse outcomes ( r=0.367, 0.471, P<0.05).Univariate analysis showed that adverse outcome group had significantly higher incidences of chorioamnionitis, seizure onset age ≤3 d, 5 min Apgar score ≤3, cranial ultrasound abnormalities, brain MR abnormalities and aEEG abnormalities than normal outcome group ( P<0.05).Logistic regression analysis showed that seizure onset age ≤3 d ( OR=3.988, 95% CI 1.376-11.674), abnormal brain MR ( OR=3.296, 95% CI 2.383-17.377) and bilirubin encephalopathy ( OR=3.792,95% CI 2.110-13.216) were independent risk factors for adverse outcomes of neonatal seizure. Conclusions:For neonatal seizure, the infants with more severe abnormal aEEG will have higher incidences of adverse outcomes and mortality. Seizure onset age ≤3 d, brain MR abnormalities and bilirubin encephalopathy were independent risk factors for adverse outcomes of neonatal seizure.
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OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.
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OBJECTIVE Epilepsy is considered a cir-cuit-level dysfunction associated with imbalanced excita-tion-inhibition,it is therapeutically necessary to identify key brain regions and related circuits in epilepsy.The subic-ulum is an essential participant in epileptic seizures,but the circuit mechanism underlying its role remains largely elusive.METHODS Here we deconstruct the diversity of subicular circuits in mouse models of epilepsy.Fiber pho-tometry was used to detect intrinsic activities of subicular PV,SST-positive interneurons and CaMK Ⅱ α-positive pyramidal neurons.Optogenetics and chemogenetics were used to selectively active or inactive subicular neu-rons or their projecting terminals.We also used in vivo and in vitro electrophysiology to record membrane charac-teristics of single neuron in distinct sub-regions of the subiculum.Finally,single pulse test was used to detect synaptic transmission strength between the subiculum and its downstream target.RESULTS First,we found that two majority of subicular interneurons,which inner-vate local pyramidal neurons to constrain their excitability,PV and SST-positive neurons showcase distinct calcium dynamics during hippocampal seizures.This could be attributed to distinct neural inputs from para-hippocampal regions of these two neuronal types.During epileptogen-esis,PV and SST neurons undergo different circuit reor-ganization patterns,that is,remarkable increase of exter-nal input to subicular PV neurons are seen after seizures,while SST cells receive decimated neural input.As their downstream targets,excitatory subicular pyramidal neu-rons are also intrinsically activated during hippocampal seizures.Moreover,we found that the subiculum hetero-geneously controls the generalization of hippocampal sei-zures by projecting to different downstream regions.No-tably,anterior thalamus projecting subicular neurons bidi-rectionally mediate seizures,while entorhinal cortex-pro-jecting subicular neurons act oppositely in seizure modu-lation.These two subpopulations are structurally and functionally dissociable.An intrinsically enhanced hyper-polarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission,thus contributing to the generalization of hippocampal seizures.CONCLUSION These results demonstrate that subicular neurons and circuits have diverse roles in epilepsy,suggesting the necessity to pre-cisely target specific subicular circuits for effective treat-ment of epilepsy.
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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.