Detection of seizures with ictal tachycardia, using heart rate variability and patient adaptive logistic regression machine learning methods: A hospital-based validation study.

OBJECTIVE: Automated seizure detection of focal epileptic seizures is needed for objective seizure quantification to optimize the treatment of patients with epilepsy. Heart rate variability (HRV)-based seizure detection using patient-adaptive threshold with logistic regression machine learning (LRML) methods has presented promising performance in a study with a Danish patient cohort. The objective of this study was to assess the generalizability of the novel LRML seizure detection algorithm by validating it in a dataset recorded from long-term video-EEG monitoring (LTM) in a Brazilian patient cohort. METHODS: Ictal and inter-ictal ECG-data epochs recorded during LTM were analyzed retrospectively. Thirty-four patients had 107 seizures (79 focal, 28 generalized tonic-clonic [GTC] including focal-to-bilateral-tonic-clonic seizures) eligible for analysis, with a total of 185.5 h recording. Because HRV-based seizure detection is only suitable in patients with marked ictal autonomic change, patients with >50 beats/min change in heart rate during seizures were selected as responders. The patient-adaptive LRML seizure detection algorithm was applied to all elected ECG data, and results were computed separately for responders and non-responders. RESULTS: The patient-adaptive LRML seizure detection algorithm yielded a sensitivity of 84.8% (95% CI: 75.6-93.9) with a false alarm rate of .25/24 h in the responder group (22 patients, 59 seizures). Twenty-five of the 26 GTC seizures were detected (96.2%), and 25 of the 33 focal seizures without bilateral convulsions were detected (75.8%). SIGNIFICANCE: The study confirms in a new, independent external dataset the good performance of seizure detection from a previous study and suggests that the method is generalizable. This method seems useful for detecting both generalized and focal epileptic seizures. The algorithm can be embedded in a wearable seizure detection system to alert patients and caregivers of seizures and generate objective seizure counts helping to optimize the treatment of the patients.

Self-reported attention and hyperactivity symptoms among adults with epilepsy.

BACKGROUND: Patients with epilepsy (PWE) frequently have comorbid psychiatric disorders, the most common of which are depression and anxiety. Attention deficit disorder with hyperactivity (ADHD) is also more frequent among PWE, though that condition has been scarcely studied among the adult PWE population. OBJECTIVE: This study aimed to compare the presence of ADHD symptoms between adult PWE and the general population. METHODS: This was an observational case-control study. Ninety-five adult PWE from a tertiary center in southern Brazil were compared with 100 healthy controls. All subjects were submitted to three structured scales: 1) the World Health Organization Adult ADHD Self-Report Scale version 1.1 (ASRS); 2) the Hospital Anxiety and Depression Scale (HADS); and 3) the Adverse Events Profile (AEP). Dichotomic variables were analyzed through chi-square test and Fisher's exact test, as appropriate, and non-parametric variables were analyzed through the Mann-Whitney U test. RESULTS: Medians and interquartile ranges (IR) were: 1) ASRS: 26.00 (IR: 18 to 38) among PWE versus 17.00 (IR: 11 to 24) among controls, p < 0.001; 2) HADS: 14.00 (IR: 8 to 21) among PWE versus 11.00 (IR: 8 to 16) among controls, p = 0.007; 3) AEP: 3800 (IR: 31 to 49) among PWE versus 33.00 (IR: 23 to 43) among controls, p = 0.001. CONCLUSION: PWE showed a higher burden of symptoms of ADHD, depression, and anxiety when compared with controls, which replicates in the Brazilian population the findings of current literature that point toward a higher prevalence of such disorders among PWE.

ANTECEDENTES: Pacientes com epilepsia (PCE) frequentemente apresentam comorbidades psiquiátricas, principalmente depressão e ansiedade. O transtorno do déficit de atenção e hiperatividade (TDAH) também é mais frequente nos PCE, porém foi pouco estudado na população adulta de PCE. OBJETIVO: Comparar a presença de sintomas de TDAH entre PCE adultos e a população geral. MéTODOS: Noventa e cinco PCE adultos de um centro terciário no Sul do Brasil foram comparados a 100 controles saudáveis. Todos os sujeitos foram submetidos a três escalas estruturadas: 1) a Escala Autorrelatada de TDAH em Adultos da Organização Mundial da Saúde, versão 1.1 (ASRS); 2) a Escala Hospitalar de Ansiedade e Depressão (HADS); e 3) o Perfil de Eventos Adversos (AEP). Variáveis dicotômicas foram analisadas através dos testes chi-quadrado e exato de Fisher, conforme apropriado, e as variáveis não paramétricas foram analisadas através do teste U de Mann-Whitney. RESULTADOS: As medianas e os intervalos interquartis (IIQ) foram: 1) ASRS: 26.00 (IIQ: 18 a 38) em PCE versus 17.00 (IIQ: 11 a 24) nos controles, p < 0,001; 2) HADS: 14.00 (IIQ: 8 a 21) em PCE versus 11.00 (IIQ: 8 a 16) nos controles, p = 0,007; 3) AEP: 38.00 (IIQ: 31 a 49) em PCE versus 33.00 (IIQ: 23 a 43) nos controles, p = 0,001. CONCLUSãO: PCE apresentaram uma maior carga de sintomas de TDAH, depressão e ansiedade quando comparados aos controles, o que replica na população brasileira os achados da literatura atual, que apontam para uma maior prevalência de tais transtornos entre PCE.

Self-reported attention and hyperactivity symptoms among adults with epilepsy / Sintomas de desatenção e hiperatividade autorrelatados entre adultos com epilepsia

Abstract Background Patients with epilepsy (PWE) frequently have comorbid psychiatric disorders, the most common of which are depression and anxiety. Attention deficit disorder with hyperactivity (ADHD) is also more frequent among PWE, though that condition has been scarcely studied among the adult PWE population. Objective This study aimed to compare the presence of ADHD symptoms between adult PWE and the general population. Methods This was an observational case-control study. Ninety-five adult PWE from a tertiary center in southern Brazil were compared with 100 healthy controls. All subjects were submitted to three structured scales: 1) the World Health Organization Adult ADHD Self-Report Scale version 1.1 (ASRS); 2) the Hospital Anxiety and Depression Scale (HADS); and 3) the Adverse Events Profile (AEP). Dichotomic variables were analyzed through chi-square test and Fisher's exact test, as appropriate, and non-parametric variables were analyzed through the Mann-Whitney U test. Results Medians and interquartile ranges (IR) were: 1) ASRS: 26.00 (IR: 18 to 38) among PWE versus 17.00 (IR: 11 to 24) among controls, p< 0.001; 2) HADS: 14.00 (IR: 8 to 21) among PWE versus 11.00 (IR: 8 to 16) among controls, p= 0.007; 3) AEP: 3800 (IR: 31 to 49) among PWE versus 33.00 (IR: 23 to 43) among controls, p= 0.001. Conclusion PWE showed a higher burden of symptoms of ADHD, depression, and anxiety when compared with controls, which replicates in the Brazilian population the findings of current literature that point toward a higher prevalence of such disorders among PWE.

Resumo Antecedentes Pacientes com epilepsia (PCE) frequentemente apresentam comorbidades psiquiátricas, principalmente depressão e ansiedade. O transtorno do déficit de atenção e hiperatividade (TDAH) também é mais frequente nos PCE, porém foi pouco estudado na população adulta de PCE. Objetivo Comparar a presença de sintomas de TDAH entre PCE adultos e a população geral. Métodos Noventa e cinco PCE adultos de um centro terciário no Sul do Brasil foram comparados a 100 controles saudáveis. Todos os sujeitos foram submetidos a três escalas estruturadas: 1) a Escala Autorrelatada de TDAH em Adultos da Organização Mundial da Saúde, versão 1.1 (ASRS); 2) a Escala Hospitalar de Ansiedade e Depressão (HADS); e 3) o Perfil de Eventos Adversos (AEP). Variáveis dicotômicas foram analisadas através dos testes chi-quadrado e exato de Fisher, conforme apropriado, e as variáveis não paramétricas foram analisadas através do teste U de Mann-Whitney. Resultados As medianas e os intervalos interquartis (IIQ) foram: 1) ASRS: 26.00 (IIQ: 18 a 38) em PCE versus 17.00 (IIQ: 11 a 24) nos controles, p< 0,001; 2) HADS: 14.00 (IIQ: 8 a 21) em PCE versus 11.00 (IIQ: 8 a 16) nos controles, p= 0,007; 3) AEP: 38.00 (IIQ: 31 a 49) em PCE versus 33.00 (IIQ: 23 a 43) nos controles, p= 0,001. Conclusão PCE apresentaram uma maior carga de sintomas de TDAH, depressão e ansiedade quando comparados aos controles, o que replica na população brasileira os achados da literatura atual, que apontam para uma maior prevalência de tais transtornos entre PCE.

Brazilian autoimmune encephalitis network (BrAIN): antibody profile and clinical characteristics from a multicenter study.

Background: The frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients. Methods: We evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed. Results: Of the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001). Conclusion: Most common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Prevalence of ictal injuries in functional (psychogenic nonepileptic) seizures: A systematic review and meta-analysis.

OBJECTIVE: Ictal injuries have long been considered typical signs of epileptic seizures. However, studies have shown that patients with functional seizures (FS)-also named psychogenic nonepileptic seizures-can also present these signs, misleading physicians and delaying a correct diagnosis. This systematic review aimed to assess the prevalence of injuries from FS. METHODS: A literature search was performed in PubMed, Embase, LILACS (Latin American and Caribbean Health Sciences Literature), Scopus, Web of Science, PsycINFO, Google Scholar, OpenGrey, and ProQuest. Observational studies were included. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for studies reporting prevalence data. RStudio was used for meta-analyses. Cumulative evidence was evaluated according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: From the 2607 identified records, 41 studies were included in the qualitative synthesis, and 28 were included in meta-analyses. A meta-analysis of 13 studies, including 1673 individuals, resulted in an overall lifetime prevalence of injuries due to FS per person of 25% (95% confidence interval [CI] = 19%-32%, I2 = 88%). Considering a limited period (video-electroencephalographic [VEEG] monitoring days), a meta-analysis of 13 studies, including 848 individuals, resulted in an injury prevalence due to FS per person of .7% (95% CI = 0%-3%, I2 = 73%). Also, a meta-analysis of eight studies, including 1000 individuals, resulted in a prevalence of injuries per FS of .1% (95% CI = 0%-.98%, I2 = 49%). The certainty in cumulative evidence assessed by GRADE was rated "very low" for lifetime prevalence of injuries per person, "low" for prevalence per person during VEEG monitoring, and "moderate" for prevalence per number of FS. SIGNIFICANCE: Overall pooled lifetime prevalence of injuries due to FS per person was 25%. In comparison, the prevalence of injuries per person during VEEG monitoring and per functional seizure was .7% and .1%, respectively. [Correction added on 07 October 2023, after first online publication: In the preceding sentence, 'consecutively' was corrected to 'respectively'.] The evidence of the occurrence of injuries due to FS breaks the paradigm that epileptic seizures can cause injuries but FS cannot.

Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group.

Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.

As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.

Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group / Terapia cetogênica na infância e adolescência: recomendações do grupo de especialistas brasileiros

Abstract Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.

Resumo As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.

Glasgow coma scale pupil score (GCS-P) and the hospital mortality in severe traumatic brain injury: analysis of 1,066 Brazilian patients.

BACKGROUND: Pupil reactivity and the Glasgow Coma Scale (GCS) score are the most clinically relevant information to predict the survival of traumatic brain injury (TBI) patients. OBJECTIVE: We evaluated the accuracy of the GCS-Pupil score (GCS-P) as a prognostic index to predict hospital mortality in Brazilian patients with severe TBI and compare it with a model combining GCS and pupil response with additional clinical and radiological prognostic factors. METHODS: Data from 1,066 patients with severe TBI from 5 prospective studies were analyzed. We determined the association between hospital mortality and the combination of GCS, pupil reactivity, age, glucose levels, cranial computed tomography (CT), or the GCS-P score by multivariate binary logistic regression. RESULTS: Eighty-five percent (n = 908) of patients were men. The mean age was 35 years old, and the overall hospital mortality was 32.8%. The area under the receiver operating characteristic curve (AUROC) was 0.73 (0.70-0.77) for the model using the GCS-P score and 0.80 (0.77-0.83) for the model including clinical and radiological variables. The GCS-P score showed similar accuracy in predicting the mortality reported for the patients with severe TBI derived from the International Mission for Prognosis and Clinical Trials in TBI (IMPACT) and the Corticosteroid Randomization After Significant Head Injury (CRASH) studies. CONCLUSION: Our results support the external validation of the GCS-P to predict hospital mortality following a severe TBI. The predictive value of the GCS-P for long-term mortality, functional, and neuropsychiatric outcomes in Brazilian patients with mild, moderate, and severe TBI deserves further investigation.

ANTECEDENTES: A reatividade pupilar e o escore da Escala de Coma de Glasgow (ECG) representam as informações clínicas mais relevantes para predizer a sobrevivência de pacientes com traumatismo cranioencefálico (TCE). OBJETIVO: Avaliar a acurácia da ECG com resposta pupilar (ECG-P) como índice prognóstico para predizer mortalidade hospitalar em pacientes brasileiros acometidos por TCE grave e compará-lo com um modelo combinando ECG e resposta pupilar com fatores prognósticos radiológicos. MéTODOS: Foram analisados dados de 1.066 pacientes com TCE grave de 5 estudos prospectivos. Foi determinada a associação entre mortalidade hospitalar e a combinação de ECG, reatividade pupilar, idade, níveis glicêmicos, tomografia computadorizada (TC) de crânio ou o escore ECG-P por regressão logística binária multivariada. RESULTADOS: Oitenta e cinco por cento (n = 908) dos pacientes eram homens. A média de idade foi de 35 anos e a mortalidade hospitalar geral foi de 32,8%. A AUROC (em português, Curva Característica de Operação do Receptor) foi de 0,73 (0,70­0,77) para o modelo utilizando o escore ECG-P e de 0,80 (0,77­0,83) para o modelo incluindo variáveis clínicas e radiológicas. O escore ECG-P mostrou acurácia semelhante na previsão da mortalidade relatada para pacientes com TCE grave derivados dos estudos International Mission for Prognosis and Clinical Trials in TBI (IMPACT, na sigla em inglês) e Corticosteroid Randomization After Significant Head Injury (CRASH, na sigla em inglês). CONCLUSãO: Nossos resultados apoiam a validação externa da ECG-P para prever a mortalidade hospitalar após um TCE grave. O valor preditivo da ECG-P para mortalidade a longo prazo, resultados funcionais e neuropsiquiátricos em pacientes brasileiros com TCE leve, moderado e grave precisam ser investigados.

Cognitive Performance of Brazilian Patients With Favorable Outcomes After Severe Traumatic Brain Injury: A Prospective Study.

OBJECTIVE: The aim of this study was to investigate the cognitive performance of patients with favorable outcomes, determined by the Glasgow Outcome Scale, 1 yr after hospital discharge due to severe traumatic brain injury. DESIGN: This was a prospective case-control study. From 163 consecutive adult patients with severe traumatic brain injury included in the study, 73 patients had a favorable outcome (Glasgow Outcome Scale score of 4 or 5) 1 yr after hospital discharge and were eligible for the cognitive evaluation, of which 28 completed the evaluations. The latter were compared with 44 healthy controls. RESULTS: The average loss of cognitive performance among participants with traumatic brain injury varied between 13.35% and 43.49% compared with the control group. Between 21.4% and 32% of the patients performed below the 10th percentile on three language tests and two verbal memory tests, whereas 39% to 50% performed below this threshold on one language test and three memory tests. Longer hospital stay, older age, and lower education were the most important predictors of worse cognitive performance. CONCLUSION: One year after a severe traumatic brain injury, a significant proportion of Brazilian patients with the favorable outcome determined by Glasgow Outcome Scale still showed significant cognitive impairment in verbal memory and language domains.

Glasgow coma scale pupil score (GCS-P) and the hospital mortality in severe traumatic brain injury: analysis of 1,066 Brazilian patients / Escala de coma de Glasgow com resposta pupilar (ECC-P) e mortalidade hospitalar em traumatismo cranioencefálico grave: análise de 1.066 pacientes brasileiros

Abstract Background Pupil reactivity and the Glasgow Coma Scale (CCS) score are the most clinically relevant information to predict the survival of traumatic brain injury (TBI) patients. Objective We evaluated the accuracy of the CCS-Pupil score (CCS-P) as a prognostic index to predict hospital mortality in Brazilian patients with severe TBI and compare it with a model combining CCS and pupil response with additional clinical and radiological prognostic factors. Methods Data from 1,066 patients with severe TBI from 5 prospective studies were analyzed. We determined the association between hospital mortality and the combination of CCS, pupil reactivity, age, glucose levels, cranial computed tomography (CT), or the CCS-P score by multivariate binary logistic regression. Results Eighty-five percent (n = 908) of patients were men. The mean age was 35 years old, and the overall hospital mortality was 32.8%. The area under the receiver operating characteristic curve (AUROC) was 0.73 (0.70-0.77) for the model using the CCS-P score and 0.80 (0.77-0.83) for the model including clinical and radiological variables. The CCS-P score showed similar accuracy in predicting the mortality reported for the patients with severe TBI derived from the International Mission for Prognosis and Clinical Trials in TBI (IMPACT) and the Corticosteroid Randomization After Significant Head Injury (CRASH) studies. Conclusion Our results support the external validation of the CCS-P to predict hospital mortality following a severe TBI. The predictive value of the CCS-P for long-term mortality, functional, and neuropsychiatric outcomes in Brazilian patients with mild, moderate, and severe TBI deserves further investigation.

Resumo Antecedentes A reatividade pupilar e o escore da Escala de Coma de Glasgow (ECC) representam as informações clínicas mais relevantes para predizer a sobrevivência de pacientes com traumatismo cranioencefálico (TCE). Objetivo Avaliar a acurácia da ECC com resposta pupilar (ECC-P) como índice prognóstico para predizer mortalidade hospitalar em pacientes brasileiros acometidos por TCE grave e compará-lo com um modelo combinando ECC e resposta pupilar com fatores prognósticos radiológicos. Métodos Foram analisados dados de 1.066 pacientes com TCE grave de 5 estudos prospectivos. Foi determinada a associação entre mortalidade hospitalar e a combinação de ECC, reatividade pupilar, idade, níveis glicêmicos, tomografia computadorizada (TC) de crânio ou o escore ECC-P por regressão logística binária multivariada. Resultados Oitenta e cinco por cento (n = 908) dos pacientes eram homens. A média de idade foi de 35 anos e a mortalidade hospitalar geral foi de 32,8%. A AUROC (em português, Curva Característica de Operação do Receptor) foi de 0,73 (0,70-0,77) para o modelo utilizando o escore ECC-P e de 0,80 (0,77-0,83) para o modelo incluindo variáveis clínicas e radiológicas. O escore ECC-P mostrou acurácia semelhante na previsão da mortalidade relatada para pacientes com TCE grave derivados dos estudos International Mission for Prognosis and Clinical Trials in TBI (IMPACT, na sigla em inglês) e Corticosteroid Randomization After Significant Head Injury (CRASH, na sigla em inglês). Conclusão Nossos resultados apoiam a validação externa da ECC-P para prever a mortalidade hospitalar após um TCE grave. O valor preditivo da ECC-P para mortalidade a longo prazo, resultados funcionais e neuropsiquiátricos em pacientes brasileiros com TCE leve, moderado e grave precisam ser investigados.

Dual assessment of abnormal cardiac electrical dispersion and diastolic dysfunction for early detection of the epileptic heart condition.

BACKGROUND: People with epilepsy (PWE) are at increased risk for premature death due to many factors. Sudden unexpected death in epilepsy (SUDEP) is among the most important causes of death in these individuals and possibly, sudden cardiac death (SCD) in epilepsy is also as important. The possibility of concurrent derangement in electrical and mechanical cardiac function, which could be a marker of early cardiac involvement in PWE, has not been investigated in that population. METHODS: Electrical dispersion indices (T-wave peak to T-wave end, TpTe; QT dispersion, QTd; QT interval corrected for heart rate, QTc) were analyzed in patients with pharmacoresistant temporal lobe epilepsy and compared to a control group. The electromechanical relationship between those indices and echocardiographic parameters were further assessed in PWE. RESULTS: In 19 PWE and 21 controls, we found greater TpTe and QTd in PWE (TpTe: 91.6 ± 16.4 ms vs. 65.2 ± 12.1 ms, p < 0.0001; and QTd: 45.3 ± 13.1 ms vs. 19 ± 6.2 ms, p < 0.0001, respectively). QTc was similar between PWE and controls (419.2 ± 31.4 ms vs. 435.1 ± 31.4 ms, p = 0.12). In multivariate linear regression, TpTe, QTc, and epilepsy duration were related to left ventricular mass; QTc was associated with left atrial volume; QTc, the number of seizures per month, epilepsy duration and antiseizure medication explained 81% of E/A mitral wave Doppler ratio. CONCLUSIONS: This is the first report to demonstrate concurrent electrical dispersion and diastolic dysfunction in PWE. These noninvasive biomarkers could prove useful in early detection of the "Epileptic Heart" condition.

What is a clinical practice guideline? A roadmap to their development. Special report from the Guidelines Task Force of the International League Against Epilepsy.

Clinical practice guidelines (CPGs) are statements that provide evidence-based recommendations aimed at optimizing patient care. However, many other documents are often published as "guidelines" when they are not; these documents, although also important in clinical practice, are usually not systematically produced following rigorous processes linking the evidence to the recommendations. Specifically, the International League Against Epilepsy (ILAE) guideline development toolkit aims to ensure that high-quality CPGs are developed to fill knowledge gaps and optimize the management of epilepsy. In addition to adhering to key methodological processes, guideline developers need to consider that effective CPGs should lead to improvements in clinical processes of care and health care outcomes. This requires monitoring the effectiveness of epilepsy-related CPGs and interventions to remove the barriers to epilepsy CPG implementation. This article provides an overview of what distinguishes quality CPGs from other documents and discusses their benefits and limitations. We summarize the recently revised ILAE CPG development process and elaborate on the barriers and facilitators to guideline dissemination, implementation, and adaptation.

Ketogenic diet, epilepsy and cognition: what do we know so far? A systematic review.

CONTEXT: Epilepsy is a chronic neurological disorder that has social, cognitive, and psychological consequences to the patient. OBJECTIVE: The effects of the ketogenic diet (KD) in children and adults with pharmacoresistant epilepsy on cognitive function were evaluated in this systematic review. DATA SOURCES: The MEDLINE, Cochrane Library, Scopus, Web of Science, and LILACS databases were searched up to February 2021. STUDY SELECTION AND DATA EXTRACTION: From the 2973 records initially identified, 24 studies were included in the systematic review. These records were screened via PICO criteria, focusing on studies that evaluated the effects of KD on cognitive function of patients with pharmacoresistant epilepsy. RESULTS: Nineteen studies described improvements in cognitive function attributed to KD; improvements were not observed in 2 studies, but neither was aggravation. Contradictory results were reported in 3 studies, depending on the method used to assess cognition. At first glance, cognitive function appears to be associated with the number of seizures, diet effectiveness, amount of carbohydrate ingested, and antiseizure medication used. However, due to the diversity of methods used to assess cognitive function, especially self-perception of cognitive improvement by the patient, it was not possible to confirm this hypothesis. CONCLUSION: It was not possible to confirm if KD itself promotes improvements in cognitive function in patients with pharmacoresistant epilepsy. Certainly, more studies are needed with better methodological quality, larger and more homogeneous samples in relation to epileptic syndrome and clinical aspects of the disease, more rigid monitoring of adherence to the diet, and use of standardized tests for neuropsychological assessment. Systematic Review Registration: PROSPERO registration no. CRD42019129236.

How predictable is heart rate variability in Brazilian patients with drug-resistant mesial temporal lobe epilepsy?

This study aimed to compare heart rate variability (HRV) in patients with drug-resistant mesial temporal lobe epilepsy (MTLE) with healthy controls and to analyze their clinical and sociodemographic variables predictive for HRV. Thirty-nine consecutive patients with drug-resistant MTLE were included in the study. The control group included twenty-seven healthy participants matched by age and gender. Seven HRV indices (HR, RR, rMSSD, SDNN, LF, HF, and LF/HF) were compared between patients and controls. The clinical and sociodemographic variables independently associated with the HRV indices were identified by multiple linear regression. In comparison with controls, the patients with MTLE showed a significant reduction in RR, rMSSD, SDNN, LF, HF, and LF/HF indices (t value 1.97-5.97, p < 0.05). Multiple regression models showed that disease duration predicted 11-22% of the analyzed HRV indices. Time domain indices showed higher association with disease duration than coefficients in frequency domain. Patients with drug-resistant MTLE present cardiac autonomic tone dysfunction, showing a significant reduction in their HRV indices (RR, SDNN, rMSSD, LF, HF, and LF/HF). Disease duration has a negative association with all HRV indices. This study contributes to understanding the relationship between MTLE and the cardiac autonomic tone, with possible implications for sudden unexpected death in epilepsy.

Efficacy and tolerability of the ketogenic diet and its variations for preventing migraine in adolescents and adults: a systematic review.

CONTEXT: Migraine is a headache of variable intensity that is associated with focal and systemic symptoms. A ketogenic diet (KD), a very-low-carbohydrate diet with a proportional increase in fat, causes brain metabolic alterations, which could be beneficial for some neurologic conditions. OBJECTIVE: A systematic review was conducted to assess the efficacy and tolerability of KD in preventing migraine in adolescents and adults. DATA SOURCES: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard was used to review articles found in the PubMed, EMBASE, Scopus, Web of Science, LILACS, LIVIVO, Science Direct, and Cochrane Central Register of Controlled Trials databases. The Google Scholar, DOAJ, ProQuest, and OpenGrey databases were included. DATA EXTRACTION: The population, intervention, comparison, outcome, and study design strategy included assessing the quality of the evidence using Grading of Recommendations Assessment Development and Evaluation and the risk of bias after applying the JBI critical appraisal tools. DATA ANALYSIS: Most of the 10 selected studies reported that KD reduced the number and severity of migraine attacks in patients, with few reported adverse effects. The evidence on the effectiveness of the KD is low, so whether the final effect is due to the treatment remains inconclusive. CONCLUSIONS: This study represents an initial effort to systematize information on the efficacy and tolerability of KD and its variations in the prevention of migraine. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020186253.

The memory assessment clinics scale for epilepsy (MAC-E): A brief measure of subjective cognitive complaints in epilepsy.

Objective: The aim of this study was to conduct item reduction of the Memory Assessment Clinics Self-Rating Scale (MAC-S) to create a briefer measure that can be used to quickly evaluate subjective memory complaints in patients with epilepsy. Method: A total of 1333 adults with focal epilepsy completed the original 49-item MAC-S. The sample was randomly split into three subsamples, and a series of analyses (i.e. exploratory factor analysis, confirmatory factor analysis, and item response theory analyses) was conducted to identify an alternative factor structure, with a reduced number of items. A panel of 5 neuropsychologists independently reviewed the final model to assess appropriateness of each individual item as well as the factor loadings and overall factor structure. Final factor titles were subsequently decided as a group. Results: Five factors were identified: Attention, Working Memory, Retrieval, Semantic Memory, and Episodic Memory. The length of the MAC-S was reduced from 49 to 30 items, with items being removed because they failed to load onto any of the factors substantially, or because of poor item discrimination or threshold levels. Conclusions: The Memory Assessment Clinics Scale for Epilepsy (MAC-E), is an updated, brief measure of subjective memory functioning that can be used to efficiently assess relevant, every-day memory abilities in patients with epilepsy within both clinical and research settings.

The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats.

We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (n = 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (n = 29). The microinfusion of ERK1/2 inhibitor (FR180204, n = 8-13/group) or MEK inhibitor (U0126, n = 8-9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (n = 9-11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear. HIGHLIGHTS: The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy. The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats. ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.

Patients with epilepsy during the COVID-19 pandemic: Depressive symptoms and their association with healthcare access.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak impacted the lives of worldwide people with epilepsy (PWE) in various aspects, particularly in those countries most significantly affected by this pandemic, such as Brazil. We aimed to investigate the prevalence of depressive symptoms in PWE and their correlation with epilepsy features and access to treatment. METHODS: PWE were invited to answer a cross-sectional online-based survey to assess and rate depressive symptoms using the NDDI-E during the first year of the COVID-19 pandemic and its relation to multiple lifestyles epilepsy clinical aspects. RESULTS: A total of 490 PWE were recruited. The prevalence of depressive symptoms during the COVID-19 pandemic was 35.3% (cutoff score > 15 on NDDI-E). The factors associated with higher NDDI-E scores were: female sex, increased seizure frequency, barriers to access to their treating physician and antiseizure medication, and unemployment. Regarding the pandemic impact on PWE healthcare, 29.2% reported restricted access to their medication, 46.1% barriers to access their physicians, 94.2% had their consultations canceled due to the pandemic, and 28.4% had seizure worsening in this period. CONCLUSION: The COVID-19 pandemic affected PWE access to the healthcare system. Depressive symptoms were more severe in patients with higher seizure frequency who had difficulties obtaining proper medical care. The COVID-19 pandemic may impact the healthcare and mental wellbeing of patients with chronic diseases such as epilepsy. Nevertheless, prospective studies on epilepsy and COVID-19 are still lacking.