Incidence and prevalence of drug-resistant epilepsy : a systematic review and meta-analysis

Objective To evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies. Methods Our protocol was registered with PROSPERO, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to perform our meta-analyses. We performed random-effects meta-regressions using study-level data. Results Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high interstudy heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0% (95% confidence interval [CI]: 16.8–34.3) in child studies but 14.6% (95% CI: 8.8–21.6) in adult/mixed age studies. The prevalence of DRE was 13.7% (95% CI: 9.2–19.0) in population/community-based populations but 36.3% (95% CI: 30.4–42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurologic deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene. Conclusions Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE

Comorbidities of epilepsy: current concepts and future perspectives

The burden of comorbidity in people with epilepsy is high. Several diseases, including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and arthritis are up to eight times more common in people with epilepsy than in the general population. Several mechanisms explain how epilepsy and comorbidities are associated, including shared risk factors and bidirectional relations. There is a pressing need for new and validated screening instruments and guidelines to help with the early detection and treatment of comorbid conditions. Preliminary evidence suggests that some conditions, such as depression and migraine, negatively affect seizure outcome and quality of life. Further investigation is needed to explore these relations and the effects of targeted interventions. Future advances in the investigation of the comorbidities of epilepsy will strengthen our understanding of epilepsy and could play an important part in stratification for genetic studies

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

IMPORTANCE: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. OBJECTIVE: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. EXPOSURES: Type of acute symptomatic seizure. MAIN OUTCOMES AND MEASURES: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). RESULTS: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. CONCLUSIONS AND RELEVANCE: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up

Health service provision for people with epilepsy in sub-Saharan Africa: A situational review

Background Epilepsy is a public health issue in sub-Saharan Africa (SSA) where many people with the condition receive no treatment. Health-care services for epilepsy in this region have not been comprehensively assessed. We examined key features of epilepsy health services provided in SSA. Methodology This was a scoping review conducted using pre-specified protocols. We implemented an electronic search strategy to identify relevant citations using PUBMED, EMBASE, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), African Index Medicus (AIM), Open Grey, Cochrane database, and Google Scholar. Articles eligible for full-text review were screened and data of interest were reported. Result The search identified 81 eligible articles, forty-nine from East Africa, 19 from West Africa, 8 from South Africa, and 5 from Central Africa. A variety of care services were identified, with reporting of rural epilepsy care in 75% of retrieved articles mainly from East and South African countries. The majority of the rural epilepsy clinics were health worker- or nurse-led, reporting good seizure control in about two-thirds of patients using phenobarbital as the most commonly prescribed antiepileptic drug. Funding for rural epilepsy care came mainly from external donor agencies. Conclusion We attempted to provide a ‘snapshot’ of epilepsy care services in SSA. The successes achieved in some of the centers are due to the use of existing primary health-care systems and employing non-physician health-care personnel. The true picture of epilepsy care coverage is not apparent due to the lack of data and proper health system structure in most parts of SSA. As more individuals begin to receive care, the long-term funding for epilepsy care in African countries will depend on the commitment of their respective governments. Watila, Musa M., et al. "Health service provision for people with epilepsy in sub-Saharan Africa: A situational review." Epilepsy & Behavior 70 (2017): 24-32. © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license

Data from: Risk factors for possible REM sleep behavior disorder: a CLSA population-based cohort study

Objective: Idiopathic REM sleep behavior disorder (RBD) is a powerful marker of prodromal neurodegenerative synucleinopathy, with 80% of patients ultimately phenoconverting to defined disease. Several environmental risk factors for RBD have been suggested, but associations vary between studies. We assessed sociodemographic, socioeconomic and clinical correlates of RBD in a 30,000-subject national cohort. Methods: Subjects aged 45-85 years in Canada were collected as part of the Canadian Longitudinal Study on Aging. Possible RBD (pRBD) was screened with the RBD-1Q, a questionnaire with 94% specificity and 87% sensitivity. To improve diagnostic reliability, subjects screening positive for apnea or non-REM parasomnia (young onset pRBD), and subjects self-reporting dementia or Parkinson’s disease were excluded. A series of sociodemographic, life style and mental health variables were analysed cross-sectionally. Potential correlates were assessed via multivariable logistic regression. Results: Of 30,097 subjects, 958 (3.2%) had pRBD. Male sex (OR=2.14 ,95%CI=[1.84, 2.49]) and lower education (OR=0.95 [0.92, 0.98] were associated with pRBD. pRBD subjects had smoked more (total smoking years OR=1.006 [1.010, 1.011]) and were more likely to be moderate-heavy drinkers (OR=1.25 [1.03, 1.50]). There was a strong association between pRBD and self-reported antidepressant treatment for depression (OR=2.76 [2.22, 3.44]), psychological distress (OR=1.52 [1.37, 1.69]), mental illness (OR=2.08 [1.79, 2.41]), and post-traumatic stress disorder (OR=2.84 [2.55, 3.54]). Conclusions: Our study replicated previous reported associations between pRBD and smoking, low education and male sex, and found previously-unreported links with alcohol use and psychological distress. The risk factors for pRBD differ from those previously defined for neurodegenerative synucleinopathies

Inter-rater reliability of risk of bias tools for non-randomized studies

Abstract Purpose There is limited knowledge on the reliability of risk of bias (ROB) tools for assessing internal validity in systematic reviews of exposure and frequency studies. We aimed to identify and then compare the inter-rater reliability (IRR) of six commonly used tools for frequency (Loney scale, Gyorkos checklist, American Academy of Neurology [AAN] tool) and exposure (Newcastle–Ottawa scale, SIGN50 checklist, AAN tool) studies. Methods Six raters independently assessed the ROB of 30 frequency and 30 exposure studies using the three respective ROB tools. Articles were rated as low, intermediate, or high ROB. We calculated an intraclass correlation coefficient (ICC) for each tool and category of ROB tool. We compared the IRR between ROB tools and tool type by inspection of overlapping ICC 95% CIs and by comparing their coefficients after transformation to Fisher’s Z values. We assessed the criterion validity of the AAN ROB tools by calculating an ICC for each rater in comparison with the original ratings from the AAN. Results All individual ROB tools had an IRR in the substantial range or higher (ICC point estimates between 0.61 and 0.80). The IRR was almost perfect (ICC point estimate > 0.80) for the AAN frequency tool and the SIGN50 checklist. All tools were comparable in IRR, except for the AAN frequency tool which had a significantly higher ICC than the Gyorkos checklist (p = 0.021) and trended towards a higher ICC when compared to the Loney scale (p = 0.085). When examined by category of ROB tool, scales, and checklists had a substantial IRR, whereas the AAN tools had an almost perfect IRR. For the criterion validity of the AAN ROB tools, the average agreement between our raters and the original AAN ratings was moderate. Conclusion All tools had substantial IRRs except for the AAN frequency tool and the SIGN50 checklist, which both had an almost perfect IRR. The AAN ROB tools were the only category of ROB tools to demonstrate an almost perfect IRR. This category of ROB tools had fewer and simpler criteria. Overall, parsimonious tools with clear instructions, such as those from the AAN, may provide more reliable ROB assessments

Sudden Death and Cardiac Arrythmia With Lamotrigine: A Rapid Systematic Review

OBJECTIVE: A recent FDA warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurological community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or electrocardiogram abnormalities. METHODS: We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies, studies of people with or without epilepsy, with one of the following outcome measures: SUDEP and sudden cardiac death, as well as the development or worsening of electrocardiogram abnormalities. All titles and abstracts were independently screened, and the full texts of relevant studies were obtained. We re-evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence. RESULTS: We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and three studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on electrocardiogram parameters, there was no statistically significant increased risk among lamotrigine users except for two studies. These two studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors felt to be more related to structural cardiac differences rather than an effect of lamotrigine. One study was rated class II while all others were class III or IV. We had "very low confidence" in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with pre-existing cardiac conditions. CONCLUSION: There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or electrocardiogram changes, in people with or without epilepsy as compared to ASM or placebo. This is due to the high risk of bias in most studies and low precision and inconsistency in the reported results