The research advance of risk factors and risk assessment of sudden unexpected death in epilepsy / 中华神经科杂志

Epilepsy is a common disease in nervous system, of which patients often present with spontaneous unpredictable spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is one of the most serious complications of epilepsy, and it is also the main cause of premature death of epileptic patients. Generalized tonic-clonic seizures, age and genetic factors are common risk factors of SUDEP. This article summarizes the classification of SUDEP and epidemiology, mechanism, risk factors, risk assessment and preventive methods of SUDEP to help physicians to understand the difference between SUDEP and sudden cardiac death.

Forensic Analysis of 9 Cases of Sudden Unexpected Death in Epilepsy / 法医学杂志

OBJECTIVES@#To analyze the case, scene and forensic pathological characteristics of sudden unexpected death in epilepsy (SUDEP), to provide a practical basis for forensic identification.@*METHODS@#A total of 9 autopsy cases of SUDEP were collected. The basic information of the cases, the scene characteristics, the forensic pathological changes, the common drugs and antiepileptic drug test results, and pericardial fluid biochemical test results were analyzed.@*RESULTS@#All of the 9 cases were male epilepsy patients died during sleep at night, the age of death was (37.1±8.6) years, and the course of epilepsy was (21.3±5.6) years. Six corpses were in prone position and three in left lateral position. The hemorrhage of the sternocleidomastoid muscle, sternal thyroid muscle and sternohyoid muscle were found with 8 cases, 5 cases and 4 cases, respectively, all of them were unilateral. Six cases had bilateral hemorrhage of pectoralis minor muscle. Brain edema, phagocytosis of frontotemporal neurons and gliosis, cardiac fibers bend in wavy patterns and eosinophilic staining enhancement, pulmonary edema, pulmonary congestion, alveolar hemorrhage, pulmonary small bronchiole wall shrinking, tubular proteinuria and pancreatic parenchymal hemorrhage were the common histopathological changes. The biochemical test results of pericardial fluid indicated that there were myocardial ischemic damage.@*CONCLUSIONS@#Young male, early onset, long course of disease, sleep in the prone position, poor drug compliance or combination, epileptic seizure may be the risk factors of SUDEP. Cardiac dysfunction and respiratory depression might be the main death mechanism of SUDEP.

Prevención de la muerte súbita en la epilepsia fármaco resistente: investigaciones de enfermería / Prevention of sudden death in drug-resistant epilepsy: nursing research

Introducción: Una muerte súbita en epilepsia (SUDEP) ocurre cada diez minutos en todo el mundo. El 30 por ciento de los pacientes epilépticos padecen de epilepsia fármaco resistente (EFR), no logran el control de sus crisis y esto aumenta el riesgo de SUDEP. Muchos aún desconocen los factores de riesgo SUDEP y cómo prevenirlos. Los tratamientos para evitarla aún son insuficientes. Las investigaciones enfermeras aportan resultados positivos en el manejo de la enfermedad. Objetivo: Revisar el estado sobre mortalidad, autogestión de epilepsia e investigaciones enfermeras para prevenir la SUDEP en adolescentes y adultos con EFR. Material y Métodos: Revisión sistemática y búsqueda bibliográfica en las bases de datos PubMed SciELO, SCOPUS, ElSEVIER, MEDES, Organización Panamericana de la Salud (OPS), INFOMED y Google académico. Los criterios de selección: trabajos de la última década en adolescentes y adultos publicados en Cuba y el mundo, enfatizando en las investigaciones enfermeras. Búsqueda de palabras claves en español e inglés, sin restricciones de idioma. Desarrollo: Entre los tratamientos para evitar la SUDEP, destacan los dispositivos de detección de crisis y programas de ayuda online, pero aún son necesarias nuevas opciones. En los factores de riesgo, destacan aquellos relacionados con el sueño. Otros factores de riesgo SUDEP pudieran ser modificables con programas educativos. A pesar de que aún se debaten las formas más adecuadas de ofrecer información sobre SUDEP, los programas educativos enfermeros han evidenciado mayor autogestión, conocimiento de la enfermedad y apego al tratamiento. Conclusiones: El enfermero es el potencial humano ideal, para implementar acciones de autocuidado en las personas con EFR, y empoderarlas con habilidades para el manejo de su enfermedad y prevención de SUDEP(AU)

Introduction: A sudden death in epilepsy (SUDEP) occurs every ten minutes worldwide. Also, 30 percent of epileptic patients who suffer from drug-resistant epilepsy (DRE) fail to control their seizures, so the risk of SUDEP increases. Many epileptic patients are unaware of the risk factors for SUDEP and the ways to prevent it. Treatments to avoid SUDEP are still insufficient. Nursing research provide positive results in the management of the disease. Objective: To review the mortality status, self-management of epilepsy and nursing research to prevent SUDEP in adolescents and adults with DRE. Material and Methods: A systematic review and bibliographic search was carried out in the PubMed SciELO, SCOPUS, ELSEVIER, MEDES, Pan American Health Organization (PAHO), INFOMED and Google Scholar databases. Selection criteria included studies on nursing research conducted in adolescents and adults during the last decade that have been published in Cuba and other countries of the world. Keywords in Spanish and English without language restrictions were used to carry out the search. Development: Crisis detection devices and online help programs stand out among the treatments to avoid SUDEP, but new options are still necessary. Among the risk factors for SUDEP, those related to sleep are highlighted. Other risk factors for SUDEP could be modified with educational programs. Despite the most appropriate ways of offering information about SUDEP are still debated, nursing educational programs have shown greater self-management, knowledge of the disease, and adherence to treatment. Conclusions: The Nurse is the ideal human potential to implement self-care actions in people with EFR. These actions aim to learn new skills for managing their disease and preventing SUDEP(AU)

Clinical and genetic analysis of Chinese patients with KCNQ2 mutation-induced neonatal/infantile epileptic disorders / 中华实用儿科临床杂志

Objective@#To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation.@*Methods@#Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.@*Results@#Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed.@*Conclusions@#This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.

Clinical and genetic analysis of Chinese patients with KCNQ2 mutation－induced neonatal/infantile epileptic disorders / 中华实用儿科临床杂志

Objective To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods Twenty－two patients were collected in the Department of Pediatrics,Peking University First Hospital from April 2007 to July 2016. The phenotype－genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 muta﹣tion was identified by the targeted next generation sequencing. Results Twenty－two de noνo KCNQ2 missense muta﹣tions from 22 patients with neonatal/infantile epileptic disorders were found. These patients had an onset of epilepsy in early infancy(median age:2 days). The seizure type of the first onset was mainly focal seizure. Atypical absence epi﹣lepsy,a novel phenotype of KCNQ2 mutation－induced epilepsies was found. The mortality of these patients was high,as 5 patients of the 22 patients died in the follow－up period,4 of which might result from sudden unexpected death in epi﹣lepsy. In the 22 patients,8 patients with anti－epileptic monotherapy became seizure－free. Of the 8 patients with a monotherapy,3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2－related epileptic disorders. These patients have high mortality. Valproate acid is the potentially effective monotherapy for these patients.

Latest progress on clinical treatment of Dravet syndrome / 中华实用儿科临床杂志

Dravet syndrome (DS) is an epileptic (developmental) encephalopathy which onsets in infancy,most DS children are drug resistant.However,the emergence of new antiepileptic drugs is providing more options to treat DS.In the recent years,the efficacy of nonpharmacologic therapies (such as neurostimulation and ketogenic diet) had been also confirmed in DS.Now,the latest progress on clinical treatment of DS was elaborated.Besides that,the therapies on neuropsychological damages and how to prevent and deal with the status epilepticus and sudden unexpected death in children with DS were briefly introduced.

Autopsy findings of SUDEP in adolescence

@#Sudden unexpected death in epilepsy (SUDEP) is a rare in children; the risk of SUDEP in children is up to 10-fold less than adults. Herein, we report a case of SUDEP in a 14-year-old boy. The post-mortem findings in neuropathological examination in SUDEP are not pathognomonic. Tongue and lip bites marks are only an indication of a seizure before death. Basically, there are no lesions that could explain the incidence of seizures before death. However, post-mortem examination is mandatory in order to determine the diagnosis of SUDEP. Autopsy, histopathological, and toxicologic examinations and a proper medical history of epilepsy are required to come to diagnosis of SUDEP. This case report further demonstrates the importance of medicolegal autopsy in allegedly dead victims.

Seizure Frequencies and Number of Anti-epileptic Drugs as Risk Factors for Sudden Unexpected Death in Epilepsy

The purpose of this study was to investigate the association between clinical variables and sudden unexpected death in epilepsy (SUDEP) and identify risk factors for SUDEP. SUDEP is one of the most frequent causes of death in patients with epilepsy. Previous studies have reported possible risk factors associated with SUDEP, but there need to be elucidated yet. The cases were 26 patients with SUDEP and three control patients were included for each case, matched for age, sex, and date of initial clinical visit. All demographic and clinical characteristics, including age, sex, disease duration, classification of epilepsy, age at seizure onset, kind and number of antiepileptic drugs, were compared between cases and controls. Seizure frequency was higher in SUDEP cases than in controls (P=0.035). Univariate analysis using conditional logistic regression showed that higher seizure frequency (odds ratio [OR]=3.1, P=0.021) and the number of antiepileptic drugs (AEDs) (OR=2.0, P=0.009) were significantly associated with SUDEP. Only the number of AEDs remained significant in multivariate analysis (OR=1.8, P=0.026). Frequent seizures and multi-drug therapy were associated with SUDEP. This may suggest that the severity of epilepsy is associated with SUDEP, regardless of the type of AED used.

Muerte súbita e inesperada en la epilepsia (sudep) / Sudden unexpected death in epilepsy

El SUDEP se refiere a la muerte súbita e inesperada con o sin testigos, no traumática, y no por ahogamientos en un paciente epiléptico, con o sin evidencia de que haya sufrido una crisis epiléptica al morir, en el que se haya descartado un estado convulsivo como causa de muerte y en el que la autopsia no proporcione evidencia alguna de una causa anatómica o tóxica de la muerte. Aunque SUDEP ha sido reconocida desde el siglo XIX, sólo en las últimas dos décadas se le ha dado la importancia que ¨¦sta requiere. La frecuencia de SUDEP depende de la severidad de la epilepsia pero en general el riesgo de muerte súbita es de 20 veces mayor que el de la población en general. El edema pulmonar neurógeno, la apnea central y la arritmia cardiaca, inducidos por una descarga Á-adrenérgica de origen central, constituyen los tres mecanismos fisiopatogínicos más estrechamente relacionados con la SUDEP. Por lo anterior obliga al clínico a realizar una minuciosa autopsia la cual deber¨ªa incluir un examen neuropatol¨®gico que documente los cambios cerebrales que subyacen a la epilepsia, toxicología y el examen del corazón, los pulmones y otros órganos.

The SUDEP refers to the sudden and unexpected death with or without witnesses, non-traumatic, and not drowning in an epileptic patient, with or without evidence that he suffered a seizure at death, in which a state is ruled seizure as the cause of death in the autopsy did not provide evidence of a toxic or anatomic cause of death. Although SUDEP has been recognized since the nineteenth century, only in the last two decades has been given the importance it requires. SUDEP frequency depends on the severity of epilepsy but in general the risk of sudden death is 20 times higher than the general population. Neurogenic pulmonary edema, central apnea and cardiac arrhythmias induced by ¦Á-adrenergic shock of central origin, pathophysiologic mechanisms are the three most closely related to SUDEP. Therefore forcing the clinician to perform a thorough autopsy, which should include neuropathological examination to document brain changes that underlie epilepsy, toxicology and examination of the heart, lungs and other organs.

Muerte súbita e inesperada en la epilepsia (SUDEP) / Sudden unexpected death in epilepsy (SUDEP)

El SUDEP se refiere a la muerte súbita e inesperada con o sin testigos, no traumática, y no por ahogamientos en un paciente epiléptico, con o sin evidencia de que haya sufrido una crisis epiléptica al morir, en el que se haya descartado un estado convulsivo como causa de muerte y en el que la autopsia no proporcione evidencia alguna de una causa anatómica o tóxica de la muerte. Aunque SUDEP ha sido reconocido desde el siglo XIX, solo en las últimas dos décadas se le ha dado la importancia que ésta requiere. La frecuencia de SUDEP depende de la severidad de la epilepsia pero en general el riesgo de muerte súbita es de 20 veces mayor que el de la población en general. El edema pulmonar neurógeno, la apnea central y la arritmia cardiaca, inducidos por una descarga a-adrenérgica de origen central, constituyen los tres mecanismos fisiopatogénicos más estrechamente relacionados con la SUDEP. Por lo anterior obliga al clínico a realizar una minuciosa autopsia la cual debería incluir un examen neuropatológico que documente los cambios cerebrales que subyacen a la epilepsia, toxicología y el examen del corazón, los pulmones y otros órganos...

Sudden unexpected death in epilepsy: an important concern

Epilepsy is one of the most common neurologic problems worldwide. Unfortunately, individuals with epilepsy are at higher risk of death than the general population, and sudden unexpected death in epilepsy is the most important direct epilepsy-related cause of death. In this review article, our research group focused on the risk factors, mechanisms and preventative measures obtained from clinical and experimental studies on sudden unexpected death in epilepsy.

Mortalidade atribuída à epilepsia, às suas doenças subjacentes ou às condições não relacionadas a ela: uma síntese / Mortality attributed to the epilepsy, its underlying diseases or the unrelated conditions to it: a synthesis

OBJETIVOS: Conhecer em relação à epilepsia: epidemiologia das causas diretas ou indiretas das mortes, inferências e críticas sobre dados de mortalidade a partir de declaração de óbitos. Refletir sobre as recomendações/alertas sobre o risco de morte prevenível a pacientes e familiares. MÉTODOS: Revisão baseada em artigos publicados principalmente nos últimos três anos a partir de busca no Pubmed com os descritores epilepsy e mortality nos títulos. Acrescentadas mais referências sobre mortalidade/declaração de óbitos, ideação suicida, profilaxia de mortes preveníveis (inquérito e medidas). RESULTADOS: Os estudos são os: com abrangência populacional a partir do Sistema de Informação em Saúde do Ministério da Saúde Brasileiro; sobre principais fatores de risco para morte prematura em pessoas com epilepsia; sobre óbitos relacionados à epilepsia (morte súbita em epilepsia - SUDEP, crise epiléptica ou estado de mal epiléptico, suicídio, acidente, cirurgia para epilepsia, estimulação nervo vago e gravidez); sobre óbitos não relacionados à epilepsia (principalmente, neoplasias, doenças cerebrovasculares, doença isquêmica coronariana e infecções respiratórias); sobre óbitos evitáveis e recomendações. CONCLUSÕES: Os pacientes com epilepsia têm a mortalidade aumentada em comparação à população geral. A questão da mortalidade aumentada ou não no pós-operatório de cirurgia para epilepsia ainda não está respondida. Os suicídios foram mais comuns particularmente nos com epilepsia refratária e/ou comorbidade psiquiátrica. SUDEP é um fenômeno epilepsia-relacionado, de maior ocorrência em pessoas jovens com epilepsia, multicausal; profilaxia das mortes evitáveis deveria ser feita pela individualização da informação a ser dada a cada paciente.

OBJECTIVE: To know regarding the epilepsy: the epidemiology of the direct or indirect causes of the deaths; inferences and critics on data about mortality from death certificates and risk factors for the deaths. To reflect on the recommendations/warnings about the risk of preventable death in patients. METHODS: Review based on articles published mainly in the last three years obtained from search in the Pubmed with the describers epilepsy and mortality in the headings. Added more references on mortality/death certificates, suicidal ideation and prophylaxis of preventable deaths (survey and measures). RESULTS: The studies are those: based on the Mortality Database of the Brazilian Ministry of Health; about main factors of risk for premature death in people with epilepsy; about mortality related to the epilepsy (sudden unexpected death in epilepsy - SUDEP, seizure and "status epilepticus", suicide, accident, surgery for epilepsy, vagal nerve stimulation and pregnancy); about unrelated mortality from the epilepsy (mainly, neoplasias, cerebrovascular disease, coronary artery disease and respiratory infection); about preventable deaths prophylaxis. CONCLUSIONS: The mortality among people with epilepsy is higher than that of the general population. The question of the increased mortality, in the postoperative period of the surgery for epilepsy, is not yet answered. The suicide occurs more often, particularly in people with refractory epilepsy and/or psychiatric comorbidities. SUDEP is an epilepsy-related phenomenon, multicausal and with higher occurrence in epileptic young people. Preventable deaths prophylaxis should be carried out by the individualization, to each patient, of the provided information.

Could sudden cardiac death in epilepsy be related to the occurrence of thalamic dysfunction or anatomic change? / A morte súbita cardíaca em epilepsia poderia estar relacionada com a ocorrência de alterações anatômicas ou funcionais do tálamo?

Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death in people with chronic epilepsy. Its physiopathology is still unknown; however, the most commonly suggested potential mechanisms involve cardiac or respiratory abnormalities. As the anatomical substrate of epileptic activity in the central nervous system (CNS) shows a direct relationship with cardiovascular alterations, this may suggests that patients with epilepsy associated with focal CNS lesions may be at particular risk of SUDEP. Currently, experimental and clinical data support an important role for thalamic nuclei in the behavioural manifestations, initiation and propagation of seizures. In view of the above findings, we purpose that SUDEP, at least in some cases, could be related to the occurrence of thalamic dysfunction or anatomic change.

A morte súbita e inesperada nas epilepsias (SUDEP) é a mais importante causa de morte em pacientes com epilepsia. A fisiopatologia da SUDEP ainda é desconhecida, no entanto, os prováveis mecanismos estão relacionados com alterações cardiovasculares ou respiratórias. Como o substrato anatômico da atividade epiléptica no sistema nervoso central (SNC) apresenta direta relação com alterações cardiovasculares, esse fato sugere que pacientes com epilepsia e lesões focais no SNC podem apresentar maior risco para SUDEP. Atualmente, dados experimentais e clínicos demonstram um importante papel dos núcleos talâmicos nas manifestações comportamentais, bem como no início e propagação das crises epilépticas. Sendo assim, nós acreditamos que a SUDEP, pelo menos em alguns casos, poderia estar relacionada com a ocorrência de alterações anatômicas ou disfunções talâmicas.

A Sudden Unexpected Death in Epilepsy / 대한간질학회지

Sudden Unexpected Death in Epilepsy (SUDEP) is defined as sudden, unexpected, non-traumatic, and non-drowning death in epilepsy. Postmortem examination must not reveal any anatomical or toxicological causes for SUDEP. The most commonly suggested mechanisms for SUDEP are cardiac abnormalities and apnea, although the cause of SUDEP is still unknown. We experienced a 36 years old male patient with epilepsy who was admitted to emergency room for cardiopulmonary arrest and the death was compatible with SUDEP because of unexpected death without reasonable explanation of cause of death except seizure. There is a possibility of an irreversible cardiac arrest or respiratory arrest by a seizure, which led to death in this case.