Identifying risk for status epilepticus with the ADAN scale: a prospective multicenter validation study. / Escala ADAN para la identificación del estado epiléptico: estudio de validación prospectivo y multicéntrico.

OBJECTIVES: Status epilepticus (SE) is a serious event associated with high mortality. This study aims to validate the recently developed ADAN (Abnormal speech, ocular Deviation, Automatisms, and Number of motor epileptic seizures) scale for detecting high risk for SE. MATERIAL AND METHODS: Prospective, multicenter, observational study in adults with suspected epileptic seizures. Consecutive recruitment took place over a 27-month period in 4 hospital emergency departments (EDs). The main endpoint was the proportion of patients with criteria for SE based on the collection and analysis of clinical characteristics and the ADAN scale criteria on arrival at the ED. RESULTS: Of the 527 patients recruited, 203 (38.5%) fulfilled the criteria that predicted SE. Multiple regression analysis demonstrated that the 4 ADAN criteria were the only variables independently associated with a final diagnosis of SE (P .001). The predictive power of the scale was 90.9% (95% CI, 88.4%-93.4%) for a final SE diagnosis. We established 3 risk groups based on ADAN scores: low (score, 0-1: 8.7%), moderate (2, 46.6%), and high (> 2, 92.6%). A cut point of more than 1 had a sensitivity of 88.2% for predicting SE, specificity of 77.8%, positive predictive value of 71.3%, and negative predictive value of 91.3%. CONCLUSION: The ADAN scale is a prospectively validated, simple clinical tool for identifying patients in the ED who are at high risk for SE.

OBJETIVO: El estado epiléptico (EE) es una enfermedad grave con elevada mortalidad. Este estudio tiene como objetivo validar la escala ADAN, propuesta recientemente para identificar pacientes con alto riesgo de desarrollar un EE. METODO: Se realizó un estudio prospectivo, multicéntrico y observacional que incluyó a pacientes adultos con sospecha de crisis epilépticas. Se llevó a cabo un reclutamiento consecutivo durante 27 meses en los servicios de urgencias (SU) de cuatro hospitales. La variable principal fue la proporción de pacientes que cumplían criterios para EE. Se han recopilado y analizado las características clínicas y la puntuación en la escala ADAN a su llegada al SU. RESULTADOS: Se reclutaron 527 pacientes, de los cuales 203 (38,5%) cumplieron criterios de EE. En el análisis de regresión múltiple, se demostró que el habla anormal, la desviación ocular, los automatismos y el número de crisis epilépticas motoras fueron las únicas variables independientemente asociadas con un diagnóstico final de EE (p 0,001). La capacidad predictiva de la escala fue del 90,9% (intervalo de confianza del 95%, 88,4-93,4) para identificar el EE como diagnóstico final. Se establecieron tres grupos de riesgo: bajo (0 1 puntos: 8,7%), moderado (2: 46,6%) y alto (> 2: 92,6%). Una puntuación de corte > 1 punto proporcionó una sensibilidad del 88,2%, especificidad del 77,8%, valor predictivo positivo del 71,3% y valor predictivo negativo del 91,3% para predecir el EE. CONCLUSIONES: La escala ADAN es una herramienta clínica simple y validada de manera prospectiva para identificar, en los SU, a los pacientes con elevado riesgo de EE.

Risk model of seizure cluster or status epilepticus and intervention in the emergency department.

OBJECTIVES: To identify possible predictors of seizure cluster or status epilepticus (SE) and to evaluate whether these patients receive greater interventions in emergency departments. METHODOLOGY: We conducted a secondary analysis of the ACESUR Registry, a multipurpose, observational, prospective, multicentre registry of adult patients with seizures from 18 emergency departments. Clinical and care-related variables were collected. We identified risk factors and risk models for seizure cluster or SE and assessed the effect of interventions by prehospital emergency services and the hospital emergency department. RESULTS: We identified a total of 186 (28%) patients from the ACESUR registry with seizure cluster (126 [19%]) or SE (60 [9%]); the remaining 478 patients (72%) had isolated seizures. The risk model for seizure cluster or SE in the emergency department included Charlson Comorbidity Index scores ≥ 3 (OR: 1.60; 95% CI, 1.05-2.46; P=.030), ≥ 2 habitual antiepileptic drugs (OR: 2.29; 95% CI, 1.49-3.51; P<.001), and focal seizures (OR: 1.56; 95% CI, 1.05-2.32; P=.027). The area under the curve of the model was 0.735 (95% CI, 0.693-0.777; P=.021). Patients with seizure cluster and SE received more aggressive interventions both by prehospital emergency services (OR: 2.89; 95% CI, 1.91-4.36; P<.001) and at the emergency department (OR: 4.41; 95% CI, 2.69-7.22; P<.001). CONCLUSIONS: This risk model may be of prognostic value in identifying adult patients at risk of presenting seizure cluster or SE in the emergency department. In our sample, these patients received more aggressive treatment than adult patients with isolated seizures before arriving at hospital, and even more so in the emergency department.

Actualización en estado epiléptico en niños. Definición, clasificación y tratamiento / Update on status epilepticus in children. Definition, clas sification and treatment

Resumen El estado epiléptico (SE) es la emergencia neurológica más frecuente en neuropediatría. Es el resultado de la falla de los mecanismos responsables en terminar una crisis epiléptica o del inicio, que conduce a una crisis epiléptica prolongada. La incidencia estimada entre 3-42 casos por cada 100.000 personas por año. Tiene una distribución bimodal afectando a los extremos de la vida; niños y ancianos, las estimaciones de mortali dad son variables en función de la edad y la etiología, en los niños la mortalidad podría ser más baja que en adultos pero alcanza una alta morbilidad hasta un 66%. La definición ha cambiado en el transcurso de los años con el fin de especificar inicio de tratamiento y comple mentar con los datos científicos se ha establecido un tiempo t1 y un t2. El tiempo (t1) es el momento cuando el tratamiento debe comenzar, que varía dependiendo de la semiología, a los 5 minutos para una crisis con vulsiva tónico clónica generalizada y a los 10 minutos para una crisis focal. El segundo tiempo (t2) se refiere al daño neuronal. El tratamiento rápido y eficaz disminuye los riesgos de complicaciones cardíacas y respiratorias, ingreso a unidades de cuidados intensivos y muerte.

Abstract Status epilepticus (SE) is the most frequent neuro logical emergency in neuropediatrics. It is the result of the failure of the mechanisms responsible for terminat ing an epileptic seizure or its onset, which leads to a prolonged epileptic seizure. The estimated incidence between 3-42 cases per 100,000 people per year. It has a bimodal distribution, affecting children and the elderly at the extremes of life. Mortality estimates are variable depending on age and etiology. Mortality in children could be lower than in adults, but it reaches a high morbidity of up to 66%. The definition has changed over the years in order to specify the start of treatment and to complement it with the scientific data, a time t1 and a t2 have been established. The time (t1) is the moment when treatment should begin, which varies depending on the semiology, at 5 minutes for a generalized tonic-clonic seizure and at 10 minutes for a focal seizure. The second time (t2) refers to neuronal damage. Prompt and effective treatment decreases the risks of cardiac and respiratory complications, admission to intensive care units, and death.

Necrosis laminar cortical cerebral como manifestación de estatus epiléptico inducido por consumo crónico de alcohol / Cortical laminar necrosis as a manifestation of status epilepticus induced by chronic alcohol abuse

Introducción: la necrosis laminar cortical es un término radiológico que describe la presencia de lesiones hiperdensas de localización cerebral, las cuales siguen una distribución giriforme y se observan con mayor sensibilidad en los estudios de resonancia magnética cerebral (RM). Esta condición patológica, que afecta a la corteza del cerebro, suele ser secundaria a una depleción de sus fuentes energéticas como consecuencia de hipoxia cerebral, alteraciones metabólicas, hipoglicemia, falla renal o hepática, intoxicaciones o infecciones. Presentación del caso: se reporta el caso de un hombre de 23 años, con antecedente de consumo crónico de alcohol, quien ingresó al servicio de urgencias de nuestra institución con un estado epiléptico. El estudio de resonancia magnética cerebral demostró la presencia de una necrosis laminar cortical con posterior déficit neurocognitivo y funcional. Conclusión: si se consideran las secuelas neurológicas potenciales asociadas a un estado epiléptico, relacionadas con necrosis laminar cortical cerebral, es necesario hacer un diagnóstico etiológico precoz, así como una atención terapéutica temprana a los pacientes.

Introduction: Cortical laminar necrosis (CLN) is radiologically defined as high-intensity cortical lesions on T1-weighted MRI images that follow a gyral distribution in the brain. Histopathologically, this pathological condition is characterized by necrosis of the cortex involving neurons, glial cells, and blood vessels. It is usually triggered by hypoxia, metabolic alterations, drugs, intoxications, or infections. Case description: We report the case of a 23-year-old man with a history of chronic alcohol abuse who was admitted to our institution with status epilepticus. The brain magnetic resonance imaging performed on this patient showed cortical laminar necrosis associated with subsequent neurocognitive deficits. Conclusion: Due to the potential neurological sequelae secondary to status epilepticus in relation to cortical laminar necrosis as permanent brain damage, it is necessary to provide early diagnosis and treatment for these patients.

Manejo del estado epiléptico en niños: encuesta en hospitales pediátricos de la Ciudad Autónoma de Buenos Aires / Management of status epilepticus in childhood: a survey conducted at pediatric hospitals in the City of Buenos Aires

Introducción. El estado epiléptico constituye la emergencia neurológica más frecuente. Si bien la mortalidad en niños es baja, su morbilidad puede superar el 20 %. Objetivo. Conocer las pautas de manejo del estado epiléptico referidas por médicos pediatras que atienden esta patología en forma habitual. Población y métodos. Estudio descriptivo, transversal, basado en una encuesta a médicos de tres hospitales pediátricos monovalentes de gestión pública de la Ciudad Autónoma de Buenos Aires. Resultados. Se administraron 292 encuestas (la tasa de respuesta completa alcanzó el 86 %); el 77 % se administró a pediatras y el 16 %, a especialistas en cuidados intensivos. Un 47 % de los participantes refiere indicar la primera benzodiacepina en el tiempo correcto; el 56 % utilizar diazepam intrarrectal en ausencia de un acceso intravenoso; el 95 % elige lorazepam como benzodiacepina inicial en caso de contar con acceso intravenoso; el 58 % refiere iniciar la etapa de fármacos de segunda línea en tiempo adecuado; el 84 % opta por fenitoína como fármaco inicial de segunda línea, un 33 % no cronometra el tiempo durante el tratamiento. La adherencia global a las recomendaciones internacionales fue del 17 %. Conclusiones. Nuestro estudio advierte una baja adherencia referida de los pediatras a las guías internacionales, en particular en las decisiones tiempo-dependientes. También se observó mayor heterogeneidad en las conductas terapéuticas a medida que se avanza en el algoritmo de tratamiento.

Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous access is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.

Tratamiento quirúrgico en estado epiléptico super refractario relacionado con malformación arterio venosa

Introducción: Las malformaciones arteriovenosas cerebrales (MAV) son un conjunto anormal de arterias y venas dilatadas del cerebro y caracterizadas por la pérdida de la organización vascular con una derivación arteriovenosa anormal. La probabilidad de ruptura de una MAV es baja, pudiendo causar déficit hasta en el 45% de los pacientes. La epilepsia puede asociarse con MAV siendo raro el estado epiléptico. La evolución a estado epiléptico refractario o estado epiléptico super refractario (EESR) es excepcional. Se presenta paciente con epilepsia asociada a MAV, con embolización y posterior complicación que evoluciona a EESR, donde se logró una resolución favorable con cirugía. Caso clínico: Paciente masculino de 70 años, con MAV temporal derecha no rota y epilepsia, libre de crisis desde el diagnóstico de ambas condiciones. Se realizó embolización logrando exclusión, pero con evolución a EESR. Tras estudio se realiza resección de MAV y resección parcial de zona de inicio de actividad epileptógena parieto-temporal. Además, se realizó una desconexión de región fronto-parietal central donde había evidencia de propagación de la actividad epiléptica. Paciente logra salir de estado crítico, con recuperación de conciencia y normalización de electroencefalogramas posquirúrgicos. A los 2 años evoluciona con epilepsia controlada (Engel IIa). Discusión y conclusiones: El abordaje quirúrgico es una opción en EESR y debe plantearse en un tiempo precoz de evolución (1-2 semanas). La cirugía se realizó para controlar EESR y fue una intervención exitosa. Esta estrategia puede lograr un cambio dramático en el pronóstico. La cirugía resectiva está indicada cuando hay evidencia etiológica en imágenes y focalidad eléctrica consistente en los estudios.

Introduction: Brain Arteriovenous Malformations (AVM) are an abnormal set of dilated arteries and veins within the brain and are characterized by loss of vascular organization with an abnormal arteriovenous shunt. The probability of AVM rupture is low, but it can cause deficits in up to 45% ofpatients. Epilepsy could be associated with AVM, and status epilepticus is rare. The evolution to refractory status epilepticus or super refractory status epilepticus (SRSE) is very rare. The objective is to present a patient with epilepsy associated with non-ruptured AVM, treated with embolization and a subsequent complication that evolves into SRSE, in which a favorable resolution was achieved after surgery Clinical case: 70-year-old male, with a diagnosis of non-ruptured right temporal AVM and epilepsy, who has been seizure free since the diagnosis, is reported. Embolization of the AVM was performed, achieving total exclusion, after the procedure presented seizures that evolved into SRSE. After investigation, an AVM resection and partial resection of the ictal onset zone on the right parieto-temporal region was performed, including a disconnection of the central fronto-parietal region, where there was evidence of propagation of ictal activity. Patient recovered from the critical condition after surgery, and also presented electrographic normalization. After 2 years, the epilepsy is well controlled (Engel IIa). Discussion and conclusions: The surgical approach is an option in SRSE, and it should be proposed early on, within a reasonable time of evolution (1-2 weeks). The active approach in this case, where the surgery was done for SRSE control, was a successful intervention. Especially when the features are consistent -there is etiological evidence in imaging and electrical focality in studies- there can be a dramatic change in the prognosis.

Status epilepticus: review on diagnosis, monitoring and treatment / Estado de mal epiléptico: revisão sobre diagnóstico, monitorização e tratamento

Abstract Status epilepticus (SE) is a frequent neurological emergency associated with high morbidity and mortality. According to the new ILAE 2015 definition, SE results either from the failure of the mechanisms responsible for seizure termination or initiation, leading to abnormally prolonged seizures. The definition has different time points for convulsive, focal and absence SE. Time is brain. There are changes in synaptic receptors leading to a more proconvulsant state and increased risk of brain lesion and sequelae with long duration. Management of SE must include three pillars: stop seizures, stabilize patients to avoid secondary lesions and treat underlying causes. Convulsive SE is defined after 5 minutes and is a major emergency. Benzodiazepines are the initial treatment, and should be given fast and an adequate dose. Phenytoin/fosphenytoin, levetiracetam and valproic acid are evidence choices for second line treatment. If SE persists, anesthetic drugs are probably the best option for third line treatment, despite lack of evidence. Midazolam is usually the best initial choice and barbiturates should be considered for refractory cases. Nonconvulsive status epilepticus has a similar initial approach, with benzodiazepines and second line intravenous (IV) agents, but after that, aggressiveness should be balanced considering risk of lesion due to seizures and medical complications caused by aggressive treatment. Usually, the best approach is the use of sequential IV antiepileptic drugs (oral/tube are options if IV options are not available). EEG monitoring is crucial for diagnosis of nonconvulsive SE, after initial control of convulsive SE and treatment control. Institutional protocols are advised to improve care.

RESUMO O estado de mal epiléptico (EME) é uma emergência frequente, com alta morbi-mortalidade. Segundo nova definição da ILAE de 2015, EME acontece pela falha dos mecanismos responsáveis ​​pelo término ou início das crises, sendo anormalmente prolongadas. Pela definição existem diferentes tempos entre EME convulsivo, focal e ausência. Tempo é cérebro. Ocorrem alterações nos receptores sinápticos, levando estado mais pró-convulsivante, com aumento risco de lesão cerebral e sequelas. O manejo do EME deve incluir três pilares: parar a crise, estabilizar o paciente para evitar lesão secundária e tratar a etiologia. EME convulsivo é definido quando duração é maior que 5 minutos e trata-se grande emergência. Os benzodiazepínicos são o tratamento inicial, devem ser administrados rapidamente e na dose adequada. Fenitoína/fosfenitoína, levetiracetam e ácido valpróico são opções com evidência para tratamento de segunda linha. Se EME persistir, uso dos anestésicos é provavelmente a melhor opção como terceira linha tratamento, apesar da falta de evidências adequadas. O midazolam costuma ser a melhor escolha inicial e os barbitúricos devem ser considerados para casos refratários. O EME não convulsivo tem abordagem inicial semelhante, com benzodiazepínicos e agentes segunda linha, mas após, a agressividade deve ser equilibrada considerando risco de lesão pelas crises e complicações pelo tratamento agressivo. A abordagem sugerida é uso de fármacos IV sequenciais (via oral/tubo quando opções IV não disponíveis). A monitorização por EEG é fundamental para o diagnóstico do EME não convulsivo, após controle inicial EME convulsivo e para controle do tratamento. Protocolos institucionais são recomendados.

Estado epiléptico refractario de inicio reciente (NORSE): caso clínico / New-onset refractory status epilepticus (NORSE): case report

El estado epiléptico refractario de inicio reciente (NORSE) es una emergencia neurológica que conlleva una elevada morbimortalidad, y como tal, genera altos costos debido a su complejo plan terapéutico y al requerimiento de una evaluación rápida y secuencial. Es una entidad clínica de mal pronóstico y su principal etiología es la encefalitis autoinmune, sin embargo, es de difícil diagnóstico y en ocasiones no se logra establecer una causa clara. Se describe el caso de una paciente joven sin antecedentes clínicos de importancia, quien presentó múltiples episodios convulsivos refractarios a anticonvulsivantes y sedación profunda, sin tolerar retiro de la sedoanalgesia por reaparición de crisis en el electroencefalograma. Presentó estudios de líquido cefalorraquídeo, infecciosos, neuroimágenes y de autoinmunidad sin alteraciones. Cursó con neumonía asociada al cuidado de la salud, que evolucionó a disfunción orgánica múltiple y fallecimiento. No se encontraron alteraciones anatomopatológicas post mortem que explicaran la causa del estado epiléptico. El estado epiléptico refractario de inicio reciente es una condición que representa un reto tanto diagnóstico como terapéutico. Se describe su abordaje diagnóstico y las opciones de tratamiento, además, se realiza una revisión corta de la literatura disponible hasta el momento

New-onset refractory status epilepticus (NORSE) is a neurological emergency with high morbidity and mortality, that results in elevated costs due to its complex therapeutic management and the requirement for a rapid and sequential evaluation. It is a condition with a poor prognosis and its main etiology is autoimmune encephalitis. However, it is difficult to diagnose and sometimes a clear cause cannot be established. The case of a young female with no relevant medical history is described. She presented multiple seizure episodes refractory to anticonvulsants and deep sedation, without tolerating withdrawal of sedoanalgesia due to reappearance of seizures in the electroencephalogram. She presented studies of cerebrospinal fluid, infections, neuroimaging and autoimmunity without alterations. She had healthcare-associated pneumonia, which progressed to multiple organ dysfunction and death. No post-mortem anatomopathological alterations were found to explain the cause of the status epilepticus. New-onset refractory status epilepticus is a condition that represents both a diagnostic and therapeutic challenge. Its diagnostic approach and treatment options are described, as well as a brief review of the available literature

Conocimiento de los residentes de especialidades médico-quirúrgicas en Colombia acerca del estado epiléptico / Knowledge regarding status epilepticus among medical-surgical specialties residents in Colombia

Introducción: el estado epiléptico es una emergencia con serias implicaciones a nivel social y económico, cuando no se maneja de manera adecuada puede llevar a la muerte. Debe abordarse por el primer especialista que tenga contacto con el paciente. En Colombia no hay estudios acerca de la adherencia a guías de práctica clínica. Objetivo: evaluar cuál es el conocimiento acerca del estado epiléptico en residentes de especialidades médico quirúrgicas en Colombia. Métodos: estudio de corte transversal descriptivo. Se aplicó una encuesta por medio de formulario google, diseñada con base en las guías de práctica clínica rutinaria para el manejo de esta patología. Resultados: respondieron la encuesta 76 residentes de neurología, medicina interna, medicina de urgencias y cuidado crítico, la edad más frecuente fue 26 a 31 años, con una relación hombre mujer de 46/54%. Discusión: las preguntas concernientes a las definiciones operativas y a los tiempos de acción fueron las que tuvieron una mejor consistencia al responderse, hay una importante falencia en la selección y uso de medicamentos anticrisis en el contexto del estado epiléptico, por lo que es importante fortalecer la educación médica en éstos aspectos académicos.

Introduction: status epilepticus is a medical emergency associated with serious social and economic implications. When not managed appropriately it may lead to death. It should be addressed promptly by the first specialist who has contact with the patient. There are no studies investigating adherence to clinical practice guidelines in Colombia. Objective: to evaluate the knowledge regarding status epilepticus among medical-surgical specialties residents in Colombia. Methods: a descriptive cross-sectional study. A survey was applied by means of a google form developed based on the routine status epilepticus clinical practice guidelines. Results: 76 neurology, internal medicine, emergency medicine and critical care residents responded to the survey. The most common age was 26 to 31 years, with a male to female ratio of 46/54%. Discussion: the questions about operational definitions and times of action were answered in a more consistent manner. There is an important limitation in the selection and use of antiseizure medications in the context of status epilepticus, so it is important to strengthen medical education in these academic aspects.

Estado epiléptico super-refratário e dieta cetogênica na unidade de terapia intensiva: relato de uma série de casos / Super-refractory status epilepticus and ketogenic diet in intensive care: a series report

RESUMO Define-se estado epiléptico super-refratário como ocorrência de crises epilépticas persistentes ou que ressurgem em condições de infusão endovenosa de anestésicos por mais de 24 horas. Nos últimos anos, chamou-se a atenção para os potenciais benefícios de uma dieta cetogênica para o controle de tais pacientes. Contudo, o papel específico dessa estratégia na população adulta, assim como o mecanismo de ação, a melhor ocasião para iniciar e o manejo das complicações, permanece como assunto amplamente debatível. Relatamos uma série de casos com três pacientes que foram internados em unidade de terapia intensiva em razão de estado epiléptico super-refratário e tratados com utilização de dieta cetogênica; também propomos uma abordagem clínica para início, transição e manejo das intercorrências clínicas desta intervenção.

Abstract Super-refractory status epilepticus is defined as seizures that persist or reemerge in the setting of an intravenous anesthetic infusion for more than 24 hours. In recent years, attention has been driven to the potential benefits of a ketogenic diet in the management of these patients. However, the specific role of this strategy in the adult population, as well as its underlying mechanism of action and optimal time for the initiation and management of complications, remain widely debatable. We report a case series of three patients admitted to an intensive care unit due to super-refractory status epilepticus who were managed with a ketogenic diet and propose a clinical approach to its initiation, transition, and management of clinical intercurrences.

Eficácia do topiramato como terapia adicional em pacientes com estado epiléptico refratário: uma breve revisão sistemática / Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review

RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: "status epilepticus", "refractory", "treatment" e "topiramate". Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.

ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

Risk model of seizure cluster or status epilepticus and intervention in the emergency department. / Modelo de riesgo de crisis en acúmulos o estado epiléptico e intervención en servicios de urgencias.

OBJECTIVES: To identify possible predictors of seizure cluster or status epilepticus (SE) and to evaluate whether these patients receive greater interventions in emergency departments. METHODOLOGY: We conducted a secondary analysis of the ACESUR Registry, a multipurpose, observational, prospective, multicentre registry of adult patients with seizures from 18 emergency departments. Clinical and care-related variables were collected. We identified risk factors and risk models for seizure cluster or SE and assessed the effect of interventions by prehospital emergency services and the hospital emergency department. RESULTS: We identified a total of 186 (28%) patients from the ACESUR registry with seizure cluster (126 [19%]) or SE (60 [9%]); the remaining 478 patients (72%) had isolated seizures. The risk model for seizure cluster or SE in the emergency department included Charlson Comorbidity Index scores≥3 (OR: 1.60; 95% CI, 1.05-2.46; P=.030), ≥2 habitual antiepileptic drugs (OR: 2.29; 95% CI, 1.49-3.51; P<.001), and focal seizures (OR: 1.56; 95% CI, 1.05-2.32; P=.027). The area under the curve of the model was 0.735 (95% CI, 0.693-0.777; P=.021). Patients with seizure cluster and SE received more aggressive interventions both by prehospital emergency services (OR: 2.89; 95% CI, 1.91-4.36; P<.001) and at the emergency department (OR: 4.41; 95% CI, 2.69-7.22; P<.001). CONCLUSIONS: This risk model may be of prognostic value in identifying adult patients at risk of presenting seizure cluster or SE in the emergency department. In our sample, these patients received more aggressive treatment than adult patients with isolated seizures before arriving at hospital, and even more so in the emergency department.

Early and late-onset nonconvulsive status epilepticus after stroke / Estado de mal epiléptico não convulsivo de ocorrência precoce e tardia após acidente vascular cerebral

ABSTRACT Background: Nonconvulsive status epilepticus (NCSE) is a condition that needs timely diagnosis and treatment. It has insignificant clinical features and presents high risk of misdiagnosis. Objective: To investigate NCSE among patients with stroke, given that stroke plays an important role in the etiology of NCSE. Methods: In this retrospective study, acute stroke patients who were admitted and followed up at a stroke outpatient clinic between January 2013 and March 2016 were included. Patients with previous histories of epilepsy, brain tumor, head trauma, hypertensive encephalopathy, arteriovenous malformation, subarachnoid hemorrhage or cerebral venous thrombosis were excluded. Demographic properties, stroke etiology, imaging method, EEG findings, stroke severity according to the NIHSS score, functional disability and modified Rankin Scale were recorded for all patients. Results: Thirty-nine out of 792 stoke patients experienced NCSE. The mean age of the study population was 70±1.2 years (min-max: 46‒90). The study population was composed of 28 females (71.8%) and 11 males (28.2%). NCSE had early onset in 23 patients (59%) and late onset in 16 (41%). The early-onset NCSE patients were older and this was statistically significant between the groups (early onset: 73.5±11.5; late onset: 65.9±12.1; p=0.04). A history of previous stroke was more frequent in the late-onset NCSE group (14; 87,5%) than in the early-onset group (11; 47.8%) (p=0.01). The prognosis was worse in the early-onset group, but without statistical significance. Conclusion: Changes in mental status in the early stages of stroke are mostly attributed to stroke itself, but NCSE should be suspected in the right clinical setting, such as in older patients with suspicious anatomical and clinical associations.

RESUMO Introdução: O Estado de Mal Não-Convulsivo (EMNC) é uma condição que necessita de diagnóstico e tratamento oportunos. Possui características clínicas insignificantes e apresenta alto risco de diagnóstico incorreto. Objetivo: Investigar o EMNC entre pacientes com acidente vascular cerebral (AVC), visto que ele desempenha um papel importante na etiologia do EMNC. Métodos: Neste estudo retrospectivo, pacientes com AVC agudo que foram admitidos e acompanhados em um ambulatório de AVC entre janeiro de 2013 e março de 2016 foram incluídos. Pacientes com história prévia de epilepsia, tumor cerebral, traumatismo cranioencefálico, encefalopatia hipertensiva, malformação arteriovenosa, hemorragia subaracnóidea ou trombose venosa cerebral foram excluídos. Propriedades demográficas, etiologia do AVC, método de imagem, achados de EEG, gravidade do AVC pela escala NIHSS, incapacidade funcional e escala de Rankin modificada foram registrados para todos os pacientes. Resultados: Um total de 39 dos 792 pacientes com AVC experimentaram EMNC. A idade média da população do estudo foi de 70±1,2 anos (mín-máx: 46‒90). A população do estudo foi composta por 28 mulheres (71,8%) e 11 homens (28,2%). O EMNC teve início precoce em 23 pacientes (59%) e início tardio em 16 (41%). Os pacientes com EMNC de início precoce eram mais velhos, o que foi estatisticamente significativo entre os grupos (início precoce: 73,5±11,5; início tardio: 65,9±12,1; p=0,04). Um histórico de AVC prévio foi mais frequente no grupo com EMNC de início tardio (14; 87,5%) do que no grupo de início precoce (11; 47,8%) (p=0,01). O prognóstico foi pior no grupo de início precoce, mas sem significância estatística. Conclusão: As alterações no estado mental nos estágios iniciais do AVC são atribuídas principalmente ao próprio AVC, mas deve-se suspeitar de EMNC com diagnóstico clínico correto, como em pacientes mais velhos com associações anatômicas e clínicas suspeitas.

Caligula: a neuropsychiatric explanation of his madness / Calígula: una explicación neuropsiquiátrica de su locura

ABSTRACT Gaius Julius Caesar Augustus Germanicus, better known as Caligula, (12 CE to 41 CE) was the third Roman emperor and ruled only four years. Throughout his life he experienced several traumatic events, and, in addition, historians mention some premorbid conditions that could cause him to become the monster that most historians know today. When Caligula was 25 years old, he suffered a near-fatal illness that turned his story around. One possible cause was lead poisoning due to the high consumption of wine, which contained lead, by Roman patricians. On the other hand, it is plausible that Caligula experienced epilepsy that began in childhood, later experienced status epilepticus in 37 CE, which triggered an epileptic psychosis with the consequent psychopathic and paranoid changes that led him to the madness noted by historians.

RESUMEN Gaius Julius Caesar Augustus Germanicus, mejor conocido como Calígula, (12 C.E. - 41 C.E.), fue el tercer emperador romano y gobernó durante apenas cuatro años. A lo largo de su vida, experimentó diferentes eventos traumáticos y, adicionalmente, algunos historiadores mencionan condiciones premórbidas que pudieron causar que se convirtiera en el monstruo que los historiadores conocen hoy. Cuando Calígula tenía 25 años, sufrió una enfermedad casi fatal que le dio un giro considerable a su historia. Una posible causa es intoxicación por plomo, debido al excesivo consumo de vino, el cual contenía considerables niveles de este metal. Por otro lado, es posible que Calígula cursara con crisis epilépticas de inicio en la infancia. Posteriormente, en el año 37 C.E. experimentara un estado epiléptico, el cual desencadenaría una psicosis epiléptica, dejando secuelas que iban a desencadenar la locura de la que muchos historiadores hablan.

Electroencephalographic findings among inpatients with COVID-19 in a tertiary hospital from a middle-income country / Achados eletroencefalográficos entre pacientes internados com COVID-19 em um hospital terciário de um país em desenvolvimento

ABSTRACT Background: In 2019, the world witnessed the emergence of a new type of coronavirus - the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spectrum of coronavirus disease 2019 (COVID-19) is variable, and amongst its manifestations are neurological implications. Objective: This report aimed to describe electroencephalographic findings in COVID-19 patients from a general tertiary hospital in São Paulo, Brazil. Methods: It was a retrospective, observational, and non-interventional study. Data were collected anonymously, comprising inpatients from Mar 1 to Jun 30, 2020, either confirmed (positive RT-PCR) or probable cases (CO-RADS 4/5) who had performed EEG during hospitalization. Results: Twenty-eight patients were enrolled, 17 (60.7%) women and 11 men, with a median age of 58 (minimum and maximum: 18-86; IQR 23.5). COVID-19 diagnosis was confirmed in 22 (78.5%). Twenty-one patients (75%) had severe disease, requiring mechanical ventilation due to acute respiratory distress syndrome (ARDS); 16 (57.1%) patients developed adjunct sepsis throughout hospitalization. There was no specific pattern found for COVID-19 in EEG. No patients presented with status epilepticus or electrographic events; most patients developed an encephalopathic pattern, as seen in most studies, with a high prevalence of altered mental status as an indication for EEG. Adjunct sepsis was associated with higher mortality. Conclusions: EEG presents as a useful tool in the context of COVID-19, as in other conditions, to differentiate nonconvulsive status epilepticus (NCSE) from encephalopathy and other causes of mental status alterations. Further studies are required to analyze whether there might be a specific EEG pattern to the disease.

RESUMO Antecedentes: Em 2019, testemunhou-se o surgimento de um novo tipo de coronavírus - o coronavírus associado à síndrome da angústia respiratória tipo 2 (SARS-CoV-2). O espectro da doença associada ao novo coronavírus, a COVID-19, é variável e, dentre suas manifestações, há implicações neurológicas. Objetivos: O presente estudo objetivou descrever achados eletroencefalográficos em pacientes com COVID-19 internados em um hospital terciário em São Paulo. Métodos: Tratou-se de estudo observacional, retrospectivo e não-intervencionista, realizado por meio de coleta anônima e retrospectiva de dados de prontuário médico de pacientes com diagnóstico confirmado (RT-PCR positivo) ou provável (CO-RADS 4 ou 5), que realizaram eletroencefalograma durante internação hospitalar. Resultados: Vinte e oito pacientes foram elencados, 17 (60,7%) mulheres e 11 homens. O diagnóstico de COVID-19 foi confirmado em 22 (78,5%) dos casos. Dos pacientes, 21 (75%) apresentaram a doença, requerendo suporte ventilatório, e 16 (57,1%) desenvolveram sepse sobreposta. Não houve padrão específico de EEG para COVID-19, e nenhum paciente apresentou estado de mal epiléptico ou crise eletrográfica; a maioria desenvolveu padrão de encefalopatia, com alentecimento da atividade cerebral, sendo a alta prevalência de alteração de estado mental a indicação para o exame. A sepse sobreposta foi associada a um pior desfecho, com maior mortalidade. Conclusão: No contexto da COVID-19, o EEG figura como ferramenta importante, auxiliando, como em outras condições, na diferenciação entre estado de mal epiléptico, encefalopatia e outras causas de alteração do estado mental. Estudos adicionais são necessários para avaliar a existência de padrão específico de alteração eletroencefalográfica na COVID-19.

Predisposing factors and impact of healthcare-associated infections in patients with status epilepticus / Factores predisponentes e impacto de las infecciones asociadas a los cuidados de salud en pacientes con estatus epiléptico

ABSTRACT Background: Few studies have evaluated the incidence, predisposing factors and impact of healthcare-associated infections (HCAIs) in relation to outcomes among patients with status epilepticus (SE). Objective: To investigate the variables associated with development of HCAIs among patients with SE and the impact of factors relating to HCAIs on mortality at three months. Methods: This study was a retrospective analysis on our prospectively collected dataset, from November 2015 to January 2019. The sample included all consecutive patients diagnosed with SE who were treated at Hospital Eugenio Espejo during that period. In total, 74 patients were included. Clinical variables such as age, etiology of SE, Charlson comorbidity index (CCI), hospital length of stay, refractory SE (RSE) and outcomes were analyzed. Results: HCAIs were diagnosed in 38 patients (51.4%), with a preponderance of respiratory tract infection (19; 25.7%). Prolonged hospital length of stay (OR=1.09; 95%CI 1.03-1.15) and CCI≥2 (OR=5.50; 95%CI 1.37-22.10) were shown to be independent variables relating to HCAIs. HCAIs were associated with an increased risk of mortality at three months, according to Cox regression analysis (OR=2.23; 95%CI 1.08-4.58), and with infection caused by Gram-negative microorganisms (OR=3.17; 95%CI 1.20-8.39). Kaplan-Meier curve analysis demonstrated that HCAIs had a negative impact on the survival rate at three months (log rank=0.025). Conclusions: HCAIs are a common complication among Ecuadorian patients with SE and were related to a lower survival rate at three months. Prolonged hospital length of stay, RSE and CCI≥2 were associated with the risk of developing HCAIs.

RESUMEN Antecedentes: Pocos estudios han evaluado la incidencia, los factores predisponentes y el impacto de las infecciones asociadas a los cuidados de salud (IACS) en pacientes con Estatus Epiléptico (EE). Objetivo: Evaluar los factores predisponentes de IACS en pacientes con EE y su impacto evolutivo después de tres meses. Métodos: Se realizó un análisis retrospectivo de los datos recogidos prospectivamente en nuestra base de datos, desde noviembre de 2015 hasta enero de 2019. Se incluyeron todos los pacientes diagnosticados y consecutivamente tratados con EE, en el Hospital Eugenio Espejo, durante ese periodo. En total, 74 pacientes fueron incluidos. Se analizaron variables clínicas y evolutivas. Resultados: Las IACS fueron identificadas en 38 pacientes (51,4%), con predominio de infecciones respiratorias (25,7%). Los factores asociados con el desarrollo IACS fueron la estadía hospitalaria prolongada (OR=1,09, IC95% 1,03-1,15) y el índice de Charlson (ICH)≥2 (OR=5,50, IC95% 1,37-22,10). La regresión de Cox demostró un incremento significativo de la mortalidad en los pacientes con IACS (OR=2,23, IC95% 1,08-4,58) y en las causadas por gérmenes gram-negativos (OR=3,17, IC95% 1,20-8,39). La curva de Kaplan Meier evidenció el impacto desfavorable de las IACS (log rank=0.025) en la evolución de los pacientes después de los tres meses. Conclusiones: Las IACS fueron complicaciones frecuentes en los pacientes ecuatorianos con EE y fueron asociadas con una menor supervivencia después de los tres meses. Las variables como la estadía hospitalaria prolongada, el EE refractario y el ICH≥2 fueron identificados como factores de riesgo para sufrir una IACS.

Estado epiléptico en adultos: caracterización de pacientes monitorizados por videoelectroencefalograma / Status epilecticus in adults: patient characterization by video-electroencephalogram monitoringby video-electroencephalogram monitoring

Introducción: el estado epiléptico (EE) es una afección potencialmente mortal con una morbilidad significativa en quienes sobreviven a esta entidad. Pacientes y métodos: estudio transversal descriptivo de corte analítico con el objetivo de describir la prevalencia y la relación con variables sociodemográficas, electroencefalográficas, imagenológicas y desenlaces clínicos en los pacientes hospitalizados que fueron monitorizado por videoelectroencefalograma (VEEG), en el Hospital de San José de Bogotá, Colombia, entre agosto 2017 y agosto 2019. Resultados: de los 135 pacientes monitorizados por VEEG, 27,47% cumplieron con los criterios para EE. La edad promedio fue 48 (DE: 19,56) años, 54,05% (n=20) de sexo masculino y 75,67% (n=28) sin antecedentes de epilepsia. Predominaron las manifestaciones motoras (70,27%, n=26), en 59,46% en el puntaje STESS fue desfavorable, 64,86% (n=24) requirió inducción a coma y monitorización en la unidad de cuidados intensivos(UCI) y 37,84% (n=14) fallecieron durante su estancia intrahospitalaria. Se encontró una relación entre EE, requerimiento de UCI y muerte intrahospitalaria. Conclusiones: la prevalencia del EE en pacientes hospitalizados monitorizados por VEEG fue cercana a 28%, lo que sugiere una relación entre EE, requerimiento de UCI y muerte intrahospitalaria.

Introduction: status epilepticus (SE) is a life-threatening disorder associated with high morbidity in SE survivors. Patients and methods: descriptive and analytical cross-sectional study with the aim to characterize the prevalence and relation with socio-demographic, electroencephalography and neuro-image variables as well as clinical outcomes of hospitalized patients who received video-electroencephalogram (video-EEG) monitoring, at Hospital de San José in Bogotá, Colombia, between August 2017 and August 2019. Results: of the 135 patients who received video-EEG monitoring, 27.47% met the criteria for SE. The median age was 48 (SD: 19.56) years, 54.05% (n=20) were men and 75.67% (n=28) had no history of epilepsy. There was a predominance of motor manifestations (70.27%, n=26), 59.46% had an unfavorable STESS score, while 64.86% (n=24) required induced coma and monitoring in the intensive care unit (ICU) and 37.84 % (n=14) died during their hospital stay. A relationship was found between SE, requiring admission to the ICU and in-hospital death. Conclusions: the prevalence of SE in hospitalized patients monitored by video-EEG was close to 28%, and a relationship between SE, requiring ICU admission and in-hospital death is suggested.

Manifestaciones neurológicas en pacientes pediátricos con COVID-19: reporte de casos

La pandemia por la COVID-19 afecta actualmente a millones de personas sin exceptuar la población pediátrica. Las manifestaciones clínicas en niños son variables: respiratorias, gastrointestinales, hematológicas, neurológicas y sistémicas. Con el objetivo de describir las diversas presentaciones clínicas y neurológicas durante la evolución de la enfermedad se documentó una serie de casos de pacientes pediátricos con la COVID-19. Se plantean diversos mecanismos a través de los cuales el SARS-CoV-2 causaría daño neurológico (daño directo, secundario a respuesta inmune, entre otras) con características clínicas variables (convulsiones, debilidad muscular, trastorno del sensorio). Los estudios sobre características clínicas y factores pronósticos en niños y adolescentes con SARS-CoV-2 son limitados, por lo cual el presente reporte contribuye con un espectro de manifestaciones neurológicas asociadas al SARS-CoV-2 en población pediátrica.

The COVID-19 pandemic currently affects millions of people including the pediatric population. The clinical manifestations in children are diverse: respiratory, gastrointestinal, hematological, neurological and systemic. In order to describe the various clinical and neurological manifestations during the evolution of the disease, we documented a series of cases of pediatric patients with COVID-19. Various mechanisms are proposed through which SARS-CoV-2 would cause neurological injury (direct injury, secondary to an immune response, among others) with variable clinical characteristics (seizures, muscle weakness, sensorial disorder). Studies on clinical characteristics and prognostic factors in children and adolescents with SARS-CoV-2 are limited, therefore, this report provides a spectrum of neurological manifestations associated with SARS-CoV-2 in pediatric population.

Uso de tarjetas de medicación en el manejo de estado epiléptico en un servicio de emergencias. Mejoras en prescripción, preparación y administración de drogas / Use of medication cards in the management of statu epilepticus at an emergency department. Improvements in drug prescription, preparation and administration

Introducción: Los errores de medicación (EM) causan una elevada morbimortalidad y generan costos innecesarios. El servicio de emergencias (SE) presenta un mayor riesgo de EM que otras áreas. El desarrollo de una herramienta que estandarice el uso de fármacos podría mejorar la seguridad y el proceso de medicación. Objetivos: Evaluar las mejoras en el proceso de medicación mediante el uso de tablas de medicación (TM) durante la atención del estado epiléptico (EE). Materiales y métodos: Se realizó un estudio de tipo antes y después no controlado. La intervención fue el desarrollo e implementación de TM. Se relevó in situ la prescripción, preparación y administración de fármacos incluidos en las TM durante segunda quincena de Octubre y mes de Noviembre 2016, previo a la implementación de la herramienta, y en el mismo período de 2017, luego de la inducción e implementación de las tablas. Se registraron los EM y se categorizaron de acuerdo a la etapa del proceso en que ocurrieron. Resultados: En el período pre-intervención se realizaron 14 registros, 86% (12) tenía al menos un error; 57% (8) errores en la etapa de prescripción, 57% (8) en la de preparación y 21% (3) en la de administración. En el período post-intervención se realizaron 17 registros, 12% (2) tenía por lo menos un EM. No se registraron errores en la fase de prescripción, hubo 12% (2) de errores de preparación y 6% (1) de administración. Conclusión: La implementación de las TM para la estandarización del uso de fármacos en EE resultó una medida muy positiva, mejorando la seguridad en el proceso de medicación (AU)

Introduction: Medication errors (ME) are associated with high morbidity mortality and lead to unnecessary costs. The risk of ME is higher at the emergency department (ED) than in other areas. Developing a tool that standardizes drug use may improve safety and medication processes. Objectives: To evaluate improvements in the medication process by using medication cards (MCs) during status epilepticus (SE) care. Materials and methods: An uncontrolled before-and-after study was conducted. The intervention was the development and implementation of MCs. The in situ prescription, preparation, and administration of drugs included in the MCs was recorded during the second half of October and November 2016, prior to the implementation of the tool, and in the same period of 2017, after the introduction and implementation of the MCs. ME were recorded and categorized according to the stage of the process in which they occurred. Results: In the pre-intervention period 14 episodes were recorded; in 86% (12) at least one error occurred; 57% (8) were ME in the prescription stage, 57% (8) were ME in the preparation stage, and 21% (3) were ME in the administration stage. In the post-intervention period 17 errors were recorded, in 12% (2) at least one ME occurred. No errors were recorded in the prescription stage, 12% (2) were preparation errors, and 6% (1) administration errors. Conclusion: The implementation of MCs for the standardization of medications used in the RU was successful, improving safety in the medication process (AU)

Covid-19 y epilepsia / COVID-19 and epilepsy

RESUMEN La encefalopatía es una manifestación neurológica frecuente en los pacientes en UCI con Covid-19. Es importante realizar un adecuado diagnóstico diferencial con el estado epiléptico no convulsivo, para poder optimizar su cuidado y pronóstico. El uso del video-electroencefalograma (VEEG) bajo adecuadas normas de bioseguridad, permite realizar un adecuado diagnóstico del estado epiléptico, disminuyendo el numero de ingresos innecesarios a la Unidad de Cuidado Intensivo, y el tiempo de sedación con anestésicos. La telemedicina para los pacientes con epilepsia ha demostrado ser una herramienta útil, al no mostrar inferioridad en comparación con las visitas cara a cara habituales en términos de diferencia significativa en el número de las crisis, hospitalizaciones, visitas a la sala de emergencias o cumplimiento de medicamentos.

SUMMARY: Encephalopathy is a frequent neurological manifestation in ICU patients with COVID-19. It is important to make an accurate differential diagnosis with non-convulsive epileptic status, in order to optimize the management and prognosis. The use of Video-EEG monitoring assuring biosecurity standards, allows an adequate diagnosis of epileptic status, reducing the number of unnecessary admissions to the intensive care unit, sedation time and anesthetics use. The use of telemedicine in patients with epilepsy has proven to be a useful tool, compared to standard outpatient visits in terms of number of seizures, admissions, emergency visits, or adherence to the medication.