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Status epilepticus (SE) is a life-threatening neurological condition with significant mortality. Rapid management is essential to minimize the mortality and disability of SE. Two recent trials provided evidence to guide SE management in early and established stages. The Rapid Anticonvulsant Medication Prior To Arrival Trial (RAMPART, 2011) showed that intramuscular midazolam is a better alternative for early convulsive SE in prehospital settings. The Established Status Epilepticus Treatment Trial (ESETT, 2020) supported the use of sodium valproate and levetiracetam as second-line treatment for its efficacy and shorter administration time. However, there are challenges to revising the status epilepticus management in resource-limited settings, in pre-hospital, first- and second-line treatment, as well as management of refractory and super-refractory SE. These challenges included restrictions or lack of training in the administration of benzodiazepine in the prehospital setting, limited availability and accessibility of newer antiseizure medications (ASMs) in emergency departments and smaller hospitals, and low clinicians' awareness of the latest evidence. A collaborative effort to educate, improve awareness, and make certain ASMs more readily available is recommended to achieve a better clinical outcome in SE.
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BACKGROUND: Mobile health (mHealth) applications (apps) show promise in supporting epilepsy self-management (eSM). To delve deeper into this potential, we conducted a systematic review of epilepsy mHealth apps available on both iOS and Android platforms, examining articles related to eSM. This review allowed us to identify important domains related to eSM. Furthermore, based on the findings, we developed an epilepsy mHealth app framework that aims to improve self-management for the local population. This study aims to assess the practicality and usability of the proposed mHealth app framework designed to improve eSM. We will conduct an expert panel review to evaluate the effectiveness and feasibility of the framework. MATERIAL AND METHODS: Content validity was assessed by an expert panel comprising epileptologists and pharmacists. The validation process involved scoring the items within each domain of the framework to evaluate their practicality and usability (quantitative component). In addition, a panel discussion was conducted to further explore and discuss the qualitative aspects of the items. RESULTS: A total of 4 domains with 15 items were highly rated for their practicality and usefulness in eSM. CONCLUSIONS: The locally validated framework will be useful for developing eSM mobile apps. Seizure Tracking, Medication Adherence, Treatment Management, and Healthcare Communication emerged as the most crucial domains for enhancing eSM.
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Epilepsia , Aplicativos Móveis , Autogestão , Telemedicina , Humanos , Epilepsia/terapia , Autogestão/métodos , Adesão à MedicaçãoRESUMO
INTRODUCTION: Depression and anxiety are prevalent in epilepsy patients, but psychiatric or psychological services may not be accessible to all patients. This study aimed to determine the effectiveness of the 20-minute mindful breathing on the psychological well-being of PWE using an instructional video. METHOD: This was a pilot, assessor-blinded, randomized controlled trial. The intervention group received a guided video and was briefed to perform the exercise twice a week for two weeks while the waitlist control group only received the video upon completion of the study. The subjects were assessed at three-time points (T0: Baseline, T1: 2 weeks after the intervention, T2: 4 weeks after intervention), using the Neurological Disorders Depression Index (NDDI-E), General Anxiety Disorder (GAD-7), Quality of Life in Epilepsy Inventory (QOLIE-31) and Mindfulness Attention Awareness Scale (MAAS). RESULTS: Twenty patients were recruited, with 10 in the intervention and waitlist-control groups. Compared with the waitlist-control group, participants in the intervention group showed significant improvement in NDDI-E at T1 (p = 0.022) but not at T2 (p = 0.056) and greater improvement in GAD-7 at T1 and T2 but not statistically significant. The QOLIE-31 overall score in the intervention group has significantly improved at T1 (p = 0.036) and T2 (p = 0.031) compared to the waitlist-control group. For MAAS, the intervention group also had an increased score at T2 (p = 0.025). CONCLUSION: The 20-minute mindfulness breathing exercise has an immediate effect in improving depression and quality of life among people with epilepsy.
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Exercícios Respiratórios , Epilepsia , Atenção Plena , Qualidade de Vida , Humanos , Masculino , Feminino , Projetos Piloto , Adulto , Epilepsia/psicologia , Epilepsia/terapia , Atenção Plena/métodos , Qualidade de Vida/psicologia , Exercícios Respiratórios/métodos , Pessoa de Meia-Idade , Depressão/terapia , Depressão/psicologia , Resultado do Tratamento , Adulto Jovem , Ansiedade/terapia , Ansiedade/psicologia , Ansiedade/etiologia , Escalas de Graduação Psiquiátrica , Bem-Estar PsicológicoRESUMO
OBJECTIVE: Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS). METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs. RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p < 0.0001) with BRV 50 mg/day and 200 mg/day, respectively, 50% responder rate was 19.0%, 41.1%, and 49.3% with placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p < 0.0001 for both BRV groups vs. placebo). Median percent reduction in FOS frequency from baseline was 21.3%/38.9%/46.7% in patients on placebo/BRV 50 mg/BRV 200 mg/day, respectively. Overall, 0, 7 (4.6%), and 10 (6.8%) patients were classified as seizure-free during the treatment period on placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p = 0.0146/p = 0.0017 for BRV 50 mg/200 mg/day vs. placebo, respectively). TEAE incidences were similar between patients on placebo (58.4%) and all patients receiving BRV (58.5%); TEAE incidences for BRV 50 mg/day and BRV 200 mg/day were 57.0% and 60.1%, respectively. Overall, 0.7% of patients on placebo and 2.0% of all patients on BRV reported serious TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 1.3% and 2.7%, respectively), 20.1% of patients on placebo and 33.1% of all patients on BRV reported drug-related TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 26.5% and 39.9%, respectively), and 4.7% of patients on placebo and 3.0% of all patients on BRV discontinued due to TEAEs (discontinuation incidences for BRV 50 mg/day and BRV 200 mg/day were 2.6% and 3.4%, respectively). SIGNIFICANCE: Adjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non-Asian populations. PLAIN LANGUAGE SUMMARY: Brivaracetam is used to treat partial or focal seizures in people with epilepsy. Most studies with brivaracetam tablets have involved people from non-Asian racial backgrounds. In this study, 449 Asian adults with epilepsy took part. One third took 50 mg of brivaracetam, one third took 200 mg of brivaracetam, and one third took a placebo each day for 12 weeks. On average, those who took brivaracetam had fewer seizures than those given the placebo. Most of the side effects were mild and the number and type of side effects seen were as expected for this medication.
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Anticonvulsivantes , Pirrolidinonas , Humanos , Método Duplo-Cego , Feminino , Masculino , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/efeitos adversos , Pessoa de Meia-Idade , Pirrolidinonas/uso terapêutico , Pirrolidinonas/administração & dosagem , Pirrolidinonas/efeitos adversos , Adulto Jovem , Idoso , Resultado do Tratamento , Quimioterapia Combinada , Convulsões/tratamento farmacológico , Adolescente , Epilepsias Parciais/tratamento farmacológico , Povo Asiático , Idoso de 80 Anos ou maisRESUMO
We investigated the COVID-19 pandemic's impact on values and religiosity in multi-ethnic Malaysia. Values were measured as changes in values, daily activities, and life priorities using a 5-point Likert scale (-2 to +2). Centrality of Religiosity Scale measured changes in religiosity. Around 176 predominantly female (66.5%), Chinese (68.2%) respondents, aged 35.5 ± 14.1 completed the survey. Most life values changed positively: a sense of security at home (2, interquartile range [IQR]: 1-2), connection with family (1, 1-2), and contribution to society (1, 1-2). Certain life priorities' importance increased: health (2, IQR 2-2), family (2, 2-2), and happiness (2, 1-2); except power and money. These significant positive changes in values and religiosity varied between genders and ethnicities.
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COVID-19 , Pandemias , Humanos , Feminino , Masculino , Religião , Inquéritos e Questionários , EtnicidadeRESUMO
Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.
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OBJECTIVE: People with epilepsy (PWE) have a high prevalence of developing depression and anxiety. The objective is to determine the feasibility of brief screening tools to screen for depression and anxiety in epilepsy, and the predictive factors. METHOD: This is a cross-sectional study in the neurology clinic in a tertiary teaching hospital in Kuala Lumpur. The screening tools used were the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the General Anxiety Disorder Form (GAD-7). RESULTS: Five hundred and eighty-five patients were recruited in this study, and 50.8% of them were male, predominantly Chinese (46.7%), with a mean age of seizure onset of 21.8 ± 16.1 years. The majority had focal seizures (75.0%), and 41.9% had seizure remission. There were 15.5% who scored ≥15 in the NDDI-E, and 17.0% had moderate or severe anxiety (scored ≥10 in the GAD-7). In a regression model to predict the NDDI-E score, the age of seizure onset recorded a higher beta value (ß = -0.265, p =< 0.001), followed by the duration of epilepsy (ß = -0.213, p =< 0.001), use of levetiracetam (LEV) (ß = 0.147, p = 0.002), clonazepam (CLZ) (ß = 0.127, p = 0.011), and lamotrigine (LTG) (ß = 0.125, p = 0.011), number of current antiseizure medications (ß = -0.124, p = 0.049), seizure remission for ≥1 year (ß = -0.108, p = 0.011), and female (ß = 0.082, p = 0.049). For the GAD-7 score, the predictors included current age (ß = -0.152, p = 0.001), the use of LEV (ß = 0.122, p = 0.011), Indian ethnicity (ß = 0.114, p = 0.006), and the use of carbamazepine (ß = -0.090, p = 0.043). CONCLUSION: Implementation of simple psychological screening using self-administered questionnaires was feasible in a busy tertiary epilepsy clinic.
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Epilepsia , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Estudos Transversais , Estudos de Viabilidade , Epilepsia/complicações , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Depressão/diagnóstico , Depressão/etiologia , Depressão/epidemiologia , Convulsões/tratamento farmacológicoRESUMO
BACKGROUND: Caregivers of adults with epilepsy (AWE) play an important role in the healthcare pathway of AWE and are described as the "co-client." Being caregivers can be stressful and the negative impacts might accumulate over time, affecting their quality of life and well-being. OBJECTIVES: This qualitative study aimed to explore the lived experience of caregivers of AWE in Malaysian families and understand their caregiving challenges. Individual semi-structured interviews were held with 12 primary caregivers of AWE. Interpretative Phenomenological Approach (IPA) was used. The interview transcripts were analyzed using NVivo12 software. RESULTS: Primary caregivers of AWE were parents or siblings, with ages ranging from 56 to 80 years old and years of caregiving from 24 to 40 years. Most AWE (58%) were intellectually disabled and fully dependent on ADL needs. Two categories of themes emerged, including four themes on caregiver burden, i.e., physical, emotional, and social burdens, and challenges in future planning of care, and two themes on coping strategies (problem- or emotional-focused). In future planning of care, most caregivers especially parents carried a burden of responsibility and were reluctant to depend on others or institutional services. CONCLUSION: The caregiving burden among caregivers for adult AWE was not confined to current burdens only but also challenges in future planning. A better understanding of the caregiving burden for AWE and coping strategies is needed to provide tailored psychoeducation or psychosocial intervention to support this population.
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Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.
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AIMS: Despite the availability of newer antiseizure medications, carbamazepine (CBZ) remains the gold standard. However, patients of Asian ancestry are susceptible to CBZ-related severe cutaneous adverse reactions. Universal HLA-B*15:02 screening is a promising intervention to address this. With the increasing recognition of integrating real-world evidence in economic evaluations, the cost-effectiveness of universal HLA-B*15:02 screening was assessed using available real-world data in Malaysia. METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate 3 strategies for treating newly diagnosed epilepsy among adults: (i) CBZ initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to CBZ initiation; and (iii) alternative prescribing without HLA-B*15:02 screening. The model was populated with real-world inputs derived from the Malaysian population. From a societal perspective, base-case analysis and sensitivity analyses estimated the costs and outcomes over a lifetime. Incremental cost-effectiveness ratios were calculated. RESULTS: In the base-cases analysis, universal HLA-B*15:02 screening yielded the lowest total costs and the highest total quality-adjusted life years (QALYs) gained. Compared with current practice, universal screening was less costly by USD100 and more effective by QALYs increase of 0.1306, while alternative prescribing resulted in 0.1383 QALYs loss at additional costs of USD332. The highest seizure remission rate (56%) was estimated for universal HLA-B*15:02 screening vs. current practice (54%) and alternative prescribing (48%). CONCLUSION: Our study suggests that universal HLA-B*15:02 screening is a cost-effective intervention in Malaysia. With the demonstrated value of real-world evidence in economic evaluations, more relevant standardization efforts should be emphasized to better inform decision-making.
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Análise de Custo-Efetividade , Síndrome de Stevens-Johnson , Adulto , Humanos , Benzodiazepinas/uso terapêutico , Carbamazepina/uso terapêutico , Análise Custo-Benefício , Antígenos HLA-B/genética , Antígeno HLA-B15/genética , Malásia/epidemiologia , Síndrome de Stevens-Johnson/epidemiologiaRESUMO
INTRODUCTION: Early and effective treatment is fundamental in status epilepticus (SE) management. At the initiative of the Epilepsy Council of Malaysia, this study aimed to determine the treatment gap in SE across different healthcare settings in Malaysia. METHODS: A web-based survey was sent to clinicians involved in the management of SE, across all states and at all levels of healthcare services. RESULTS: A total of 158 responses were received from 104 health facilities, including 23 tertiary government hospitals (95.8% of all government tertiary hospitals in Malaysia), 4 (80.0%) universities, 14 (6.7%) private, 15 (11.5%) district hospitals and 21 clinics. Intravenous (IV) diazepam was available in 14 (93.3%) district and 33 (80.5%) tertiary hospitals for prehospital management. Non-IV benzodiazepine (rectal diazepam and intramuscular midazolam) was not widely available in prehospital services (75.8% and 51.5%). Intramuscular midazolam was underutilised (60.0% in district and 65.9% in tertiary hospitals). IV sodium valproate and levetiracetam were only available in 66.7% and 53.3% of the district hospitals, respectively. Electroencephalogram (EEG) services were available in only 26.7% of the district hospitals. Non-pharmacological therapies such as ketogenic diet, electroconvulsive therapy, and therapeutic hypothermia were not available in most district and tertiary hospitals for refractory and super-refractory SE. CONCLUSIONS: We identified several gaps in the current practice of SE management, including limited availability and underutilization of non-IV midazolam in prehospital services, underutilization of non-IV midazolam and other second-line ASMs, and lack of EEG monitoring in district hospitals and limited treatment options for refractory and super-refractory SE in tertiary hospitals.
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Anticonvulsivantes , Estado Epiléptico , Humanos , Anticonvulsivantes/uso terapêutico , Midazolam/uso terapêutico , Malásia/epidemiologia , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico , DiazepamRESUMO
20% of brain tumor patients present with seizures at the onset of diagnosis, while a further 25-40% develop epileptic seizures as the tumor progresses. Tumor-related epilepsy (TRE) is a condition in which the tumor causes recurring, unprovoked seizures. The occurrence of TRE differs between patients, along with the effectiveness of treatment methods. Therefore, determining the tumor properties that correlate with epilepsy can help guide TRE treatment. This article reviews the MRI sequences and image post-processing algorithms in the study of TRE. It focuses on epilepsy caused by glioma tumors because it is the most common type of malignant brain tumor and it has a high prevalence of epilepsy. In correlational TRE studies, conventional MRI sequences and diffusion-weighted MRI (DWI) are used to extract variables related to the tumor radiological characteristics, called imaging factors. Image post-processing is used to correlate the imaging factors with the incidence of epilepsy. The earlier studies of TRE used univariate and multivariate analysis to study the correlations between specific variables and incidence of epilepsy. Later, studies used voxel-based morphometry and voxel lesion-symptom mapping. Radiomics has been recently used to post-process the images for the study of TRE. This article will discuss the limitation of the existing imaging modalities and post-processing algorithms. It ends with some suggestions and challenges for future TRE studies.
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OBJECTIVE: One of the objectives of the Intersectoral Global Action Plan on epilepsy and other neurological disorders for 2022 to 2031 is to ensure at least 80% of people with epilepsy (PWE) will have access to appropriate, affordable, and safe antiseizure medications (ASMs) by 2031. However, ASM affordability is a significant issue in low- and middle-income countries, preventing PWE from accessing optimal treatment. This study aimed to determine the affordability of the newer (second and third generation) ASMs in resource-limited countries in Asia. METHODS: We conducted a cross-sectional survey by contacting country representatives in lower-middle-income countries (LMICs) in Asia, including Indonesia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Vietnam, India, Bangladesh, and Pakistan, and the upper-middle-income country Malaysia, from March 2022 to April 2022. The affordability of each ASM was calculated by dividing the 30-day ASM cost by the daily wage of the lowest paid unskilled laborers. Treatment costing 1 day's wage or less for a 30-day supply of chronic disease is considered affordable. RESULTS: Eight LMICs and one upper-middle-income country were included in this study. Lao PDR had no newer ASM, and Vietnam had only three newer ASMs. The most frequently available ASMs were levetiracetam, topiramate, and lamotrigine, and the least frequently available was lacosamide. The majority of the newer ASMs were unaffordable, with the median number of days' wages for a 30-day supply ranging from 5.6 to 14.8 days. SIGNIFICANCE: All new generation ASMs, whether original or generic brands, were unaffordable in most Asian LMICs.
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Anticonvulsivantes , Epilepsia , Humanos , Estudos Transversais , Ásia , Índia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Custos e Análise de CustoRESUMO
Epilepsy is a complex neurological disease that can be caused by both genetic and environmental factors. Many studies have been conducted to investigate the genetic risk variants and molecular mechanisms of epilepsy. Disruption of excitation-inhibition balance (E/I balance) is one of the widely accepted disease mechanisms of epilepsy. The maintenance of E/I balance is an intricate process that is governed by multiple proteins. Using whole exome sequencing (WES), we identified a novel GABRA1 c.448G>A (p.E150K) variant and ERBB4 c.1972A>T (p.I658F, rs190654033) variant in a Malaysian Chinese family with genetic generalized epilepsy (GGE). The GGE may be triggered by dysregulation of E/I balance mechanism. Segregation of the variants in the family was verified by Sanger sequencing. All family members with GGE inherited both variants. However, family members who carried only one of the variants did not show any symptoms of GGE. Both the GABRA1 and ERBB4 variants were predicted damaging by MutationTaster and CADD, and protein structure analysis showed that the variants had resulted in the formation of additional hydrogen bonds in the mutant proteins. GABRA1 variant could reduce the efficiency of GABAA receptors, and constitutively active ERBB4 receptors caused by the ERBB4 variant promote internalization of GABAA receptors. The interaction between the two variants may cause a greater disruption in E/I balance, which is more likely to induce a seizure. Nevertheless, this disease model was derived from a single small family, further studies are still needed to confirm the verifiability of the purported disease model.
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Epilepsia Generalizada , Epilepsia , Humanos , Epilepsia Generalizada/genética , Epilepsia/genética , Convulsões , Família , Receptores de GABA-A/genética , Receptores de GABA-A/química , Ácido gama-Aminobutírico , Receptor ErbB-4/genéticaRESUMO
OBJECTIVES: Prevalence of seizures in brain tumors vary substantially between studies even with similar histopathological types. We aimed to identify the seizure prevalence of the commonest types of brain tumors. METHODS: Systematic computerized search of PubMed, Embase, and Web of Science were performed. The meta-analysis of pooled prevalence and 95 % confidence interval (CI) for tumor-related seizures were calculated by using a random effect model. Based on the 2014 epilepsy definition, a mean seizure prevalence of 60 % is used to indicate high seizure prevalence in this study. RESULTS: 74 studies that reported seizure prevalence with 23,116 patients were included in this meta-analysis. These tumors has higher seizure incidence rate (at least 60 %) with pooled prevalence of 63 % for adult with low-grade astrocytoma (95 % CI: 57-68 %), 65 % for oligodendroglioma (95% CI: 57-72 %), 72 % for oligoastrocytoma (95 % CI: 67-77 %), 81 % for ganglioglioma (95 % CI: 66-97 %) and 94 % for DNET (94 % CI: 83-100 %). CONCLUSION: This study highlights the type of brain tumors that carry a high seizure prevalence. Screening for subtle seizures and early management of seizures may be beneficial in patients with low-grade astrocytoma (adult), oligodendroglioma, oligoastrocytoma, ganglioglioma or DNET brain tumor.
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Astrocitoma , Neoplasias Encefálicas , Ganglioglioma , Oligodendroglioma , Adulto , Humanos , Oligodendroglioma/complicações , Prevalência , Convulsões/etiologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Astrocitoma/complicações , Astrocitoma/epidemiologiaRESUMO
OBJECTIVE: Although epilepsy surgery is more effective than medical therapy for drug-resistant patients, it is underutilized in both high-income and low- and middle-income countries. In light of our efforts to establish an epilepsy surgery program in a resource-limited setting, this study aimed to determine the outcome of the epilepsy surgery program in Ho Chi Minh City (HCMC), Vietnam. METHODS: In 2018, we developed the HCMC epilepsy core multidisciplinary team with members from various hospitals and centers. The team typically included neurologists, neurosurgeons, neuropsychologists, psychiatrists, and nursing specialists. Presurgical evaluations were performed for patients with drug-resistant epilepsy, fulfilling the ILAE criteria, with an epileptogenic lesion (mesial temporal sclerosis, low-grade gliomas, or focal cortical dysplasia). All epilepsy surgeries were performed in two epilepsy surgery centers in HCMC between 2018 and 2021. The patients were followed up for at least 12 months. RESULTS: Fifty-two patients with drug-resistant epilepsy underwent presurgical evaluation, of which 35 underwent surgery. Among the 52 patients, 20 (38.5%) underwent surgery after showing concordance among the results of standard presurgical assessments such as semiology, scalp interictal or ictal electroencephalography, and brain imaging. Among the 26 people with epilepsy who required more advanced evaluations, 15 underwent surgery with intraoperative electrocorticography to delineate the optimal resection borders. The outcomes of Engel Class I and Class II were achieved in 29/35 (82.8%) and 6/35 (17.2%) patients, respectively. SIGNIFICANCE: The epilepsy surgery program with a multicentered collaborative model in a resource-limited setting showed favorable outcomes in HCMC, Vietnam.
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Epilepsia Resistente a Medicamentos , Epilepsia , Malformações do Desenvolvimento Cortical , Humanos , Vietnã , Epilepsia/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , EletrocorticografiaRESUMO
PURPOSE: Seizures are a common presenting symptom among patients with low- and high-grade glioma. However, the impact and inter-relationship between the presence of seizures, anti-seizure medication (ASM) and survival are unclear. We retrospectively analyzed the incidence of seizures and identified the pattern and relationship of anti-seizure medication on survival in our cohort of patients with glioma. METHODS: We evaluated all glioma patients who underwent treatment at the University of Malaya Medical Centre (UMMC) between 2008 and 2020. Demographic and clinical data of seizures and pattern of ASM administration in comparison to overall survival were analyzed. RESULTS: A total of 235 patients were studied, with a minimum of one year clinical follow-up post-treatment. The median survival for low-grade glioma was 38 months whereas high-grade glioma was 15 months. One-third of our glioma patients (n = 74) presented with seizures. All patients with seizures and a further 31% of patients without seizures were started on anti-seizure medication preoperatively. Seizure and Levetiracetam (LEV) were significantly associated with OS on univariate analysis. However, only LEV (HR 0.49; 95% CI 0.23-0.87; p=0.02) was significantly associated with improving overall survival (OS) on multivariate analysis. Once ASM was adjusted for relevant factors and each other, LEV was associated with improved survival in all grade gliomas (HR 0.52; 95% CI 0.31-0.88; p=0.02) and specifically high-grade gliomas (HR 0.53; 95% CI 0.30-0.94; p=0.03). CONCLUSIONS: Pre-operative seizures among patients with glioma indicated a better overall prognosis. The administration of ASM, specifically LEV was associated with a significant survival advantage in our retrospective cohort of patients.
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Neoplasias Encefálicas , Glioma , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Glioma/complicações , Glioma/tratamento farmacológico , Humanos , Levetiracetam/uso terapêutico , Estudos RetrospectivosRESUMO
Importance: Selection of antiseizure medications (ASMs) for epilepsy remains largely a trial-and-error approach. Under this approach, many patients have to endure sequential trials of ineffective treatments until the "right drugs" are prescribed. Objective: To develop and validate a deep learning model using readily available clinical information to predict treatment success with the first ASM for individual patients. Design, Setting, and Participants: This cohort study developed and validated a prognostic model. Patients were treated between 1982 and 2020. All patients were followed up for a minimum of 1 year or until failure of the first ASM. A total of 2404 adults with epilepsy newly treated at specialist clinics in Scotland, Malaysia, Australia, and China between 1982 and 2020 were considered for inclusion, of whom 606 (25.2%) were excluded from the final cohort because of missing information in 1 or more variables. Exposures: One of 7 antiseizure medications. Main Outcomes and Measures: With the use of the transformer model architecture on 16 clinical factors and ASM information, this cohort study first pooled all cohorts for model training and testing. The model was trained again using the largest cohort and externally validated on the other 4 cohorts. The area under the receiver operating characteristic curve (AUROC), weighted balanced accuracy, sensitivity, and specificity of the model were all assessed for predicting treatment success based on the optimal probability cutoff. Treatment success was defined as complete seizure freedom for the first year of treatment while taking the first ASM. Performance of the transformer model was compared with other machine learning models. Results: The final pooled cohort included 1798 adults (54.5% female; median age, 34 years [IQR, 24-50 years]). The transformer model that was trained using the pooled cohort had an AUROC of 0.65 (95% CI, 0.63-0.67) and a weighted balanced accuracy of 0.62 (95% CI, 0.60-0.64) on the test set. The model that was trained using the largest cohort only had AUROCs ranging from 0.52 to 0.60 and a weighted balanced accuracy ranging from 0.51 to 0.62 in the external validation cohorts. Number of pretreatment seizures, presence of psychiatric disorders, electroencephalography, and brain imaging findings were the most important clinical variables for predicted outcomes in both models. The transformer model that was developed using the pooled cohort outperformed 2 of the 5 other models tested in terms of AUROC. Conclusions and Relevance: In this cohort study, a deep learning model showed the feasibility of personalized prediction of response to ASMs based on clinical information. With improvement of performance, such as by incorporating genetic and imaging data, this model may potentially assist clinicians in selecting the right drug at the first trial.
Assuntos
Aprendizado Profundo , Epilepsia , Adulto , Inteligência Artificial , Estudos de Coortes , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Aprendizado de Máquina , MasculinoRESUMO
BACKGROUND: Periventricular nodular heterotopia (PVNH) is caused by abnormal neuronal migration, resulting in the neurons accumulate as nodules along the surface of the lateral ventricles. PVNH often cause epilepsy, psychomotor development or cognition problem. Mutations in FLNA (Filamin A) is the most common underlying genetic etiology. Our purpose is to delineate the clinical and imaging spectrum that differentiates FLNA-positive and FLNA-negative PVNH patients. METHODS: We included 21 patients with confirmed PVNH. The detailed clinical information, electroencephalography, and other clinical findings were recorded. Detailed brain MR imaging was assessed. Mutation analysis of the FLNA gene was used Sanger sequencing or a next generation sequencing based assay. RESULTS: FLNA mutations were identified in 9 patients (7 females and 2 males), including two nonsense, two splice site, three frameshift, and two missense mutations. In FLNA-positive group, 8 patients had anterior predominant bilateral symmetric presentation and only one had asymmetrical distribution and dilated ventricles. Extra-cerebral features were more often observed in FLNA-positive group than FLNA-negative group. CONCLUSION: Genetics of PVNH is heterogenous, and mutations in FLNA gene account for less than half of the patients in our cohort. Our finding between FLNA-positive and FLNA-negative patients could guide the clinicians to select relevant genetic testing.