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How to Do a Systematic Review: A Best Practice Guide for Conducting and Reporting Narrative Reviews, Meta-Analyses, and Meta-Syntheses. Annual review of psychology Systematic reviews are characterized by a methodical and replicable methodology and presentation. They involve a comprehensive search to locate all relevant published and unpublished work on a subject; a systematic integration of search results; and a critique of the extent, nature, and quality of evidence in relation to a particular research question. The best reviews synthesize studies to draw broad theoretical conclusions about what a literature means, linking theory to evidence and evidence to theory. This guide describes how to plan, conduct, organize, and present a systematic review of quantitative (meta-analysis) or qualitative (narrative review, meta-synthesis) information. We outline core standards and principles and describe commonly encountered problems. Although this guide targets psychological scientists, its high level of abstraction makes it potentially relevant to any subject area or discipline. We argue that systematic reviews are a key methodology for clarifying whether and how research findings replicate and for explaining possible inconsistencies, and we call for researchers to conduct systematic reviews to help elucidate whether there is a replication crisis. 10.1146/annurev-psych-010418-102803
A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research. European journal of epidemiology To inform evidence-based practice in health care, guidelines and policies require accurate identification, collation, and integration of all available evidence in a comprehensive, meaningful, and time-efficient manner. Approaches to evidence synthesis such as carefully conducted systematic reviews and meta-analyses are essential tools to summarize specific topics. Unfortunately, not all systematic reviews are truly systematic, and their quality can vary substantially. Since well-conducted evidence synthesis typically involves a complex set of steps, we believe formulating a cohesive, step-by-step guide on how to conduct a systemic review and meta-analysis is essential. While most of the guidelines on systematic reviews focus on how to report or appraise systematic reviews, they lack guidance on how to synthesize evidence efficiently. To facilitate the design and development of evidence syntheses, we provide a clear and concise, 24-step guide on how to perform a systematic review and meta-analysis of observational studies and clinical trials. We describe each step, illustrate it with concrete examples, and provide relevant references for further guidance. The 24-step guide (1) simplifies the methodology of conducting a systematic review, (2) provides healthcare professionals and researchers with methodologically sound tools for conducting systematic reviews and meta-analyses, and (3) it can enhance the quality of existing evidence synthesis efforts. This guide will help its readers to better understand the complexity of the process, appraise the quality of published systematic reviews, and better comprehend (and use) evidence from medical literature. 10.1007/s10654-019-00576-5
Gender and psychiatric disorders in children with epilepsy. A meta-analysis. Lax-Pericall Maria Teresa,Bird Victoria,Taylor Eric Epilepsy & behavior : E&B OBJECTIVE:The objective of the study was to assess the influence of gender on psychiatric disorders in children with epilepsy (CWE). METHOD:A systematic review of the literature on risk factors for psychiatric disorder in CWE published between 2004 and June 2018 was undertaken. Studies including data on gender that permitted the calculation of a risk ratio (RR) were included in the meta-analysis. A meta-regression was conducted to examine the contribution of setting of the survey and the inclusion of learning disabilities. RESULTS:Thirty-nine papers were included in the review. The male/female RR in CWE for Attention Deficit Hyperactivity Disorder (ADHD) was 1.49 (Confidence Interval (CI): 1.24-1.79), autistic spectrum disorder (ASD) 1.67 (CI: 1.47 to 1.90), anxiety 1.00 (CI: 0.90-1.12), and depression 0.93 (CI 0.41-2.09). More boys than girls had ADHD and ASD, but in relative terms, the RR male/female was lower in CWE than the RR in the general population reported in other studies. Meta-regression indicated that the inclusion of children with intellectual disability (mental retardation) or the setting (community vs hospital) did not have a significant impact. CONCLUSION:Compared with girls in the general population, girls with epilepsy seem to be at a higher risk of being diagnosed with ADHD/ASD as the gender ratio is more equal. This could be related to differences in the assessment of CWE and/or a shared pathogenesis between psychiatric conditions and epilepsy. 10.1016/j.yebeh.2019.02.014
Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta-analysis. Rosati Anna,Ilvento Lucrezia,Lucenteforte Ersilia,Pugi Alessandra,Crescioli Giada,McGreevy Kathleen S,Virgili Gianni,Mugelli Alessandro,De Masi Salvatore,Guerrini Renzo Epilepsia OBJECTIVE:To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years). METHODS:Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction. RESULTS:We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies. SIGNIFICANCE:This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria. 10.1111/epi.13981
Inflammatory mediators in human epilepsy: A systematic review and meta-analysis. de Vries Evelien E,van den Munckhof Bart,Braun Kees P J,van Royen-Kerkhof Annet,de Jager Wilco,Jansen Floor E Neuroscience and biobehavioral reviews BACKGROUND:Accumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy. METHODS:We performed a systematic review and meta-analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis. RESULTS:66 articles reporting on 1934 patients were included. IL-1ra, IL-1β, IL-6, IL-10, IFN-γ and TNF-α were the most extensively investigated proteins. Elevated levels for IL-1ra, IL-1β, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL-1α, IL-7 and IL-13, as well as the chemokines CCL2-5, -19 and -22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1β and IL-10. CONCLUSION:Inflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment. 10.1016/j.neubiorev.2016.02.007
Facial emotion perception in patients with epilepsy: A systematic review with meta-analysis. Edwards Michelle,Stewart Elizabeth,Palermo Romina,Lah Suncica Neuroscience and biobehavioral reviews Facial emotion perception is a fundamental social competency relying on a specialised, yet distributed, neural network. This review aimed to determine whether patients with epilepsy have facial emotion perception accuracy impairments overall, or for a subset of emotions (anger, disgust, happiness, sadness, fear, and surprise), and the relationship to epilepsy type, demographic/treatment variables, and brain organisation. Database searches used PRISMA guidelines with strict inclusion/exclusion criteria. Thirty included studies assessed patients with temporal lobe (TLE; n=709), frontocentral (FCE; n=22), and genetic generalised (GGE; n=48) epilepsy. Large deficits emerged in patients with epilepsy compared to controls (n=746; Hedges' g=0.908-1.076). Patients with TLE were significantly impaired on all emotions except surprise; patients with GGE were significantly impaired in anger, disgust, and fear perception. Meta-regression of patients with TLE revealed younger age at testing was associated with lower accuracy. This review provides evidence for marked global deficits of emotion perception in epilepsy, with differential emotion-specific impairment patterns in patients with TLE and GGE. 10.1016/j.neubiorev.2017.10.013
Systematic review and network meta-analysis of resective surgery for mesial temporal lobe epilepsy. Jain Puneet,Tomlinson George,Snead Carter,Sander Beate,Widjaja Elysa Journal of neurology, neurosurgery, and psychiatry OBJECTIVE:To evaluate the effectiveness of anterior temporal lobectomy (ATL) versus selective amygdalohippocampectomy (SAH) on seizure-free outcome in patients with temporal lobe epilepsy, using both direct and indirect evidence from the literature. METHODS:MEDLINE, Embase and Cochrane databases were searched for original research articles and systematic reviews comparing ATL versus SAH, and ATL or SAH versus medical management (MM). The outcome was seizure freedom at 12 months of follow-up or longer. Direct pairwise meta-analyses were conducted, followed by a random-effect Bayesian network meta-analysis (NMA) combining direct and indirect evidence. RESULTS:Twenty-eight articles were included (18 compared ATL vs SAH, 1 compared ATL vs SAH vs MM, 8 compared ATL vs MM, and 1 compared SAH vs MM). Direct pairwise meta-analyses showed no significant differences in seizure-free outcome of ATL versus SAH (OR 1.14, 95% CI 0.93 to 1.39; p=0.201), but the odds of seizure-free outcome were higher for ATL versus MM (OR 29.16, 95% CI 10.44 to 81.50; p<0.00001), and SAH versus MM (OR 28.42, 95% CI 10.17 to 79.39; p<0.00001). NMA also showed that the odds of seizure-free outcome were no different in ATL versus SAH (OR 1.15, 95% credible interval (CrI) 0.84-1.15), but higher for ATL versus MM (OR 27.22, 95% CrI 15.38-27.22), and SAH versus MM (OR 23.57, 95% CrI 12.67-23.57). There were no significant differences between direct and indirect comparisons (all p>0.05). CONCLUSION:Direct evidence, indirect evidence and NMA did not identify a difference in seizure-free outcome of ATL versus SAH. 10.1136/jnnp-2017-317783
Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis. Lattanzi Simona,Brigo Francesco,Trinka Eugen,Zaccara Gaetano,Cagnetti Claudia,Del Giovane Cinzia,Silvestrini Mauro Drugs BACKGROUND:Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability. OBJECTIVE:The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques. METHODS:Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs). RESULTS:Four trials involving 550 patients with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1-31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8-28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07-2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55-8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28-7.41; p = 0.657) and 4.20 (95% CI 1.82-9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87-16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22-12.86; p = 0.626) and 6.89 (95% CI 2.28-20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11-1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. CONCLUSIONS:Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo. 10.1007/s40265-018-0992-5
Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with focal epilepsy: A systematic review and meta-analysis. Bourdillon Pierre,Cucherat Michel,Isnard Jean,Ostrowsky-Coste Karine,Catenoix Hélène,Guénot Marc,Rheims Sylvain Epilepsia OBJECTIVE:Despite the increasing number of studies reporting results of stereo-electroencephalography (SEEG)-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) in the treatment of patients with drug-resistant focal epilepsy, the exact efficacy of this approach remains unclear. The seizure-freedom rate varies greatly across studies and the factors associated with efficacy have not been formally investigated. METHODS:All prospective or retrospective studies reporting efficacy and/or safety of SEEG-guided RF-TC in patients with drug-resistant focal epilepsy were included. The primary outcome was the seizure-free rate 1 year after the procedure. Secondary outcomes were (1) the responder rate 1 year after the procedure and (2) the proportion of patients with permanent neurologic deficit 1 year after the procedure. Each outcome was assessed in all patients and in 4 groups of patients defined by the etiology of epilepsy. Each outcome was pooled using inverse variance weighting, logit transformation of proportion, and a random-effects model. RESULTS:No prospective study was identified and a total of 6 retrospective studies, reporting efficacy and safety data of 296 patients, were included. The pooled rate of permanent neurologic deficit was 2.5% (95% confidence interval [CI] 1.2%-5.3%), without heterogeneity across studies. In contrast, both the seizure-free and responder rates varied greatly across studies, and statistical heterogeneity was high. The pooled seizure-free and responder rates were 23% (95% CI 8%-50%) and 58% (95% CI 36%-77%), respectively. Both for the seizure-free and responder rates, the greatest efficacy was observed in patients with periventricular nodular heterotopia and the lowest in patients with normal magnetic resonance imaging (MRI) findings. SIGNIFICANCE:SEEG-guided RF-TC is a safe procedure with low risk of complications. In contrast, the level of evidence regarding its efficacy remains low. Better identification of factors associated with seizure outcome are needed. 10.1111/epi.14584
Diagnostic and prognostic value of noninvasive long-term video-electroencephalographic monitoring in epilepsy surgery: A systematic review and meta-analysis from the E-PILEPSY consortium. Kobulashvili Teia,Kuchukhidze Giorgi,Brigo Francesco,Zimmermann Georg,Höfler Julia,Leitinger Markus,Dobesberger Judith,Kalss Gudrun,Rohracher Alexandra,Neuray Caroline,Wakonig Antonia,Ernst Florian,Braun Kees P J,Mouthaan Brian E,Van Eijsden Pieter,Ryvlin Philippe,Cross J Helen,Trinka Eugen, Epilepsia OBJECTIVE:The European Union-funded E-PILEPSY network (now continuing within the European Reference Network for rare and complex epilepsies [EpiCARE]) aims to harmonize and optimize presurgical diagnostic procedures by creating and implementing evidence-based guidelines across Europe. The present study evaluates the current evidence on the diagnostic accuracy of long-term video-electroencephalographic monitoring (LTM) in identifying the epileptogenic zone in epilepsy surgery candidates. METHODS:MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched for relevant articles. First, we used random-effects meta-analytical models to calculate pooled estimates of sensitivity and specificity with respect to postsurgical seizure freedom. In a second phase, we analyzed individual patient data in an exploratory fashion, assessing diagnostic accuracy within lesional and nonlesional temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE) patients. We also evaluated seizure freedom rate in the presence of "localizing" or "nonlocalizing" LTM within each group. The quality of evidence was assessed using the QUADAS-2 tool and the GRADE approach. RESULTS:Ninety-four studies were eligible. Forty-four were included in sensitivity meta-analysis and 34 in specificity meta-analysis. Pooled sensitivity was 0.70 (95% confidence interval [CI] = 0.60-0.80) and specificity was 0.40 (95% CI = 0.27-0.54). Subgroup analysis was based on individual data of 534 patients (41% men). In lesional TLE patients, sensitivity was 0.85 (95% CI = 0.81-0.89) and specificity was -0.19 (95% CI = 0.13-0.28). In lesional ETLE patients, a sensitivity of 0.47 (95% CI = 0.36-0.58) and specificity of 0.35 (95% CI = 0.21-0.53) were observed. In lesional TLE, if LTM was localizing and concordant with resection site, the seizure freedom rate was 247 of 333 (74%), whereas in lesional ETLE it was 34 of 56 (61%). The quality of evidence was assigned as "very low." SIGNIFICANCE:Long-term video-electroencephalographic monitoring is associated with moderate sensitivity and low specificity in identification of the epileptogenic zone. Sensitivity is remarkably higher in lesional TLE compared to lesional ETLE. Substantial heterogeneity across the studies indicates the need for improved design and quality of reporting. 10.1111/epi.14598
The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis. Kalilani Linda,Sun Xuezheng,Pelgrims Barbara,Noack-Rink Matthias,Villanueva Vicente Epilepsia OBJECTIVE:The definition of drug-resistant epilepsy (DRE) affects case identification and treatment, and impacts prevalence or incidence estimates and health burden estimation in epidemiology. The objective of this systematic review is to evaluate the consistency between definitions of DRE in the literature and the official definition in the International League Against Epilepsy (ILAE) guidelines, and to estimate the incidence, prevalence, and risk factors for DRE. METHODS:MEDLINE and EMBASE were searched for observational studies of DRE published between January 1980 and July 2015. The definitions of DRE in these studies were compared with the definition in the ILAE guidelines. Random-effect model meta-analyses were used to generate pooled estimates of prevalence or incidence and pooled odds ratios of the association with risk factors. RESULTS:Thirty-five studies met inclusion criteria, including 13 080 epilepsy patients and 3941 patients with DRE. The definition of DRE varied widely across studies, with only 12% meeting the requirements of the ILAE definition. The pooled prevalence proportion of DRE among epilepsy patients was 0.30 (95% confidence interval [CI] 0.19-0.42), and the pooled incidence proportion was 0.15 (95% CI 0.11-0.19). Age at onset, symptomatic epilepsy, abnormal neuroimaging findings, abnormal electroencephalography results, history of mental retardation, neuropsychiatric disorders, febrile seizure, and status epilepticus increased risk for DRE. SIGNIFICANCE:There are limited high-quality data available on DRE. Lack of consistency in definitions limits the ability to obtain robust estimates on the burden of DRE. More data based on the ILAE definition from well-designed epidemiologic studies are needed to generate accurate and reliable results. 10.1111/epi.14596
Epilepsy in hemiplegic migraine: Genetic mutations and clinical implications. Prontera P,Sarchielli P,Caproni S,Bedetti C,Cupini L M,Calabresi P,Costa C Cephalalgia : an international journal of headache Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach. 10.1177/0333102416686347
Prevalence and risk factors for autism spectrum disorder in epilepsy: a systematic review and meta-analysis. Strasser Lauren,Downes Michelle,Kung Jane,Cross J Helen,De Haan Michelle Developmental medicine and child neurology AIM:To assess the prevalence and risk factors for autism spectrum disorder (ASD) in epilepsy, and to better understand the relationship and comorbidity between these disorders. METHOD:PsychINFO and PubMed were searched for articles published in the past 15 years that examined the prevalence of ASD in individuals with epilepsy. RESULTS:A total of 19 studies were found with a pooled ASD prevalence of 6.3% in epilepsy. When divided by type, the risks of ASD for general epilepsy, infantile spasms, focal seizures, and Dravet syndrome were 4.7%, 19.9%, 41.9%, and 47.4% respectively. Studies with populations under 18 years showed a 13.2 times greater risk of ASD than study populations over 18 years, and samples with most (>50%) individuals with intellectual disability showed a greater risk 4.9 times higher than study populations with a minority of individuals with intellectual disability. The main risk factors for ASD reported in the 19 studies included presence of intellectual disability, sex, age, and symptomatic aetiology of epilepsy. INTERPRETATION:Current research supports a high prevalence of ASD in epilepsy. This study helps to define the clinical profile of patients with epilepsy who are at risk for ASD, which may help clinicians in early screening and diagnosis of ASD in this population. WHAT THIS PAPER ADDS:Critical evaluation of previous studies examining the prevalence of autism spectrum disorder (ASD) in individuals with epilepsy. A meta-analysis of 19 studies showed a pooled ASD prevalence of 6.3% in individuals with epilepsy. Studies that included a majority of individuals with intellectual disability or younger population age had a higher prevalence of autism. Risk factors reported in studies included presence of intellectual disability, sex, age, and symptomatic epilepsy origin. 10.1111/dmcn.13598
Antiepileptic drugs as prophylaxis for de novo brain tumour-related epilepsy after craniotomy: a systematic review and meta-analysis of harm and benefits. Mirian Christian,Møller Pedersen Maria,Sabers Anne,Mathiesen Tiit Journal of neurology, neurosurgery, and psychiatry OBJECTIVES:To investigate potential harm and benefits of antiepileptic drugs (AED) given prophylactically to prevent de novo brain tumour-related epilepsy after craniotomy. METHODS:Randomised controlled trials (RCT) and retrospective studies published before 27 November 2018 were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied. Eligible patients were diagnosed with a brain tumour, were seizure naïve and underwent craniotomy. The random effects model was used for quantitative synthesis. The analysis was adjusted for the confounding effect of including patients with a history of seizure prior to study inclusion. RESULTS:A total of 454 patients received prophylactic AED whereas 333 were allocated to placebo or no treatment. Two RCTs and four retrospective studies were identified. The OR was 1.09 (95% CI 0.7 to 1.8, p=0.7, I=5.6%, χ p=0.5), indicating study consistency and no significant differences. An additional two RCTs and one retrospective study combined craniotomy and diagnostic biopsy, and were subgroup analysed-which supported no difference in odds for epilepsy. CONCLUSIONS:A prophylactic effect of AED could not be demonstrated (nor rejected statistically). Levetiracetam was associated with less adverse effects than phenytoin. The potential harm of AED was not balanced by the potential prophylactic benefit. This study suggests that prophylactic AED should not be administered to prevent brain tumour-related epilepsy after craniotomy. 10.1136/jnnp-2018-319609
Epilepsy duration and seizure outcome in epilepsy surgery: A systematic review and meta-analysis. Bjellvi Johan,Olsson Ingrid,Malmgren Kristina,Wilbe Ramsay Karin Neurology OBJECTIVE:To conduct a systematic review and meta-analysis on the effect of earlier or later resective epilepsy surgery on seizure outcome. METHODS:We searched the electronic databases PubMed, EMBASE, and Cochrane Library for studies investigating the association of epilepsy duration and seizure freedom after resective surgery. Two reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias. We combined data in meta-analyses using a random effects model. We assessed the certainty of evidence according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS:Twenty-five studies were included, 12 of which had data suitable for meta-analyses. Comparing seizure outcome if epilepsy surgery was performed before vs after 2, 5, 10, and 20 years of epilepsy duration, and comparing epilepsy duration <5 years to >10 years, we found significant effects favoring shorter duration with risk differences ranging from 0.15 to 0.21 and risk ratios ranging from 1.20 to 1.33 ( < 0.01 for all comparisons). According to GRADE, we found low certainty of evidence favoring shorter epilepsy duration before surgery. CONCLUSION:People with shorter epilepsy duration are more likely to be seizure-free at follow-up. Furthermore, there is a positive association between shorter duration and seizure freedom also for very long epilepsy durations. Patients who might benefit from epilepsy surgery should therefore be referred for presurgical assessments without further delay, regardless of epilepsy duration. The low certainty of evidence acknowledges concerns regarding study heterogeneity and possible residual confounding. 10.1212/WNL.0000000000007753
The medical treatment of epilepsy in the elderly: A systematic review and meta-analysis. Lezaic Nastasija,Gore Geneviève,Josephson Colin B,Wiebe Samuel,Jetté Nathalie,Keezer Mark R Epilepsia OBJECTIVE:To evaluate the efficacy and tolerability of antiepileptic drugs (AEDs) in elderly individuals with epilepsy. METHODS:We searched four electronic databases as well as bibliographies and conference abstracts. Published and unpublished, randomized, or quasirandomized trials reporting the use of AEDs in people aged at least 60 years with epilepsy were eligible for inclusion. Two authors independently carried out each stage of the review. Meta-analyses were performed using random-effects models. RESULTS:Three thousand four hundred seventeen titles and abstracts were reviewed. Eighteen studies evaluating 12 AEDs met all eligibility criteria. Ten studies, comprising 1999 subjects, were suitable for meta-analysis. Among the elderly with epilepsy, lamotrigine (LTG) is better tolerated relative to carbamazepine (pooled weighted risk ratio [RR] of experiencing withdrawal due to adverse events = 1.83, 95% confidence interval [CI] = 1.23-2.43). There is a higher probability, although with a 95% CI of borderline importance, of seizure freedom when comparing levetiracetam to LTG (RR = 0.83, 95% CI = 0.68-0.97). Single studies provide evidence for the efficacy and/or tolerability of other AEDs in the elderly, including brivaracetam, gabapentin, lacosamide, perampanel, and topiramate. The risk of bias of the included studies was frequently low or unclear, although there was on occasion a high risk of bias (especially with regard to selective reporting). SIGNIFICANCE:There is some evidence for AED use in the elderly with epilepsy. More evidence is required, comparing newer AEDs to prior generations as well as examining the effects of determinants such as frailty, to guide clinicians when treating this rapidly growing patient population. 10.1111/epi.16068
Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Ryvlin Philippe,Cucherat Michel,Rheims Sylvain The Lancet. Neurology BACKGROUND:Sudden unexpected death in epilepsy (SUDEP) represents the main cause of death in patients with refractory epilepsy. No evidence-based intervention to prevent SUDEP exists. We postulated that pooling data from randomised placebo-controlled trials in patients with refractory epilepsy might show a lower incidence of SUDEP in patients receiving antiepileptic drugs (AEDs) at efficacious doses than in those receiving placebo. METHODS:We searched Medline and the Cochrane Library for randomised trials investigating any AED in the add-on treatment of drug-resistant epilepsy in adults. We extracted the number and causes of death in patients allocated to AEDs at doses that were more efficacious than placebo against seizures, AEDs at non-efficacious doses, and placebo. In our primary analysis, we compared the occurrence of definite or probable SUDEP between patients given efficacious AED doses and those given placebo using the Mantel-Haenszel method, with exclusion of trials with no event. FINDINGS:Data of 33 deaths, including 20 deemed as SUDEP, were extracted from 112 eligible randomised trials. 18 deaths were classified as definite or probable SUDEP and two as possible SUDEP. Definite or probable SUDEP, all SUDEP, and all causes of death were significantly less frequent in the efficacious AED group than in the placebo group, with odds ratios of 0·17 (95% CI 0·05-0·57, p=0·0046), 0·17 (0·05-0·57, p=0·0046), and 0·37 (0·17-0·81, p=0·0131), respectively. Rates of definite or probable SUDEP per 1000 person-years were 0·9 (95% CI 0·2-2·7) in patients who received efficacious AED doses and 6·9 (3·8-11·6) in those allocated to placebo. INTERPRETATION:Treatment with adjunctive AEDs at efficacious doses may have reduced the incidence of definite or probable SUDEP by more than seven times compared with placebo in patients with previously uncontrolled seizures. This result provides evidence in favour of active treatment revision for patients with refractory epilepsy. FUNDING:None. 10.1016/S1474-4422(11)70193-4
Medical vs. invasive therapy in AVM-related epilepsy: Systematic review and meta-analysis. Josephson Colin B,Sauro Khara,Wiebe Samuel,Clement Fiona,Jette Nathalie Neurology OBJECTIVE:To compare invasive arteriovenous malformation (AVM) therapy to conservative management using only antiepileptic drugs (AEDs) for achieving seizure freedom in patients with AVM-related epilepsy. METHODS:We searched Medline, Embase, and Cochrane Central up to June 2015 using epilepsy and AVM Medical Subject Headings and keywords. We included original research involving controlled observational cohort studies or randomized controlled trials (RCTs) comparing seizure outcomes between invasive AVM treatments vs. AED management alone, and uncontrolled case series of invasive AVM therapy for seizures that contained ≥20 patients. The estimates of seizure freedom were pooled using meta-analysis for the controlled trials, while the estimates for the case series were evaluated using descriptive statistics. RESULTS:Of 2,166 identified abstracts, 98 were reviewed in full text, of which 31 were included in the final dataset. We identified 2 controlled observational studies (n = 106 patients) and 29 uncontrolled case series. We identified 1 RCT but it did not report seizure outcomes. The pooled risk ratio for seizure freedom in controlled studies (0.99; 95% confidence interval [CI] 0.69, 1.43) did not indicate superiority to either approach. Seizure freedom in case series varied from 19% (95% CI 11, 30%) to 95% (95% CI 76, 99%) at last follow-up. CONCLUSIONS:There is insufficient evidence available to determine if invasive AVM management is superior to AED only for controlling seizures. An RCT of interventional vs. medical management using standardized epilepsy-specific presurgical protocols is warranted. 10.1212/WNL.0000000000002240
Epilepsy, excess deaths and years of life lost from external causes. Nevalainen Olli,Simola Mikko,Ansakorpi Hanna,Raitanen Jani,Artama Miia,Isojärvi Jouko,Auvinen Anssi European journal of epidemiology We systematically quantified excess mortality in epilepsy patients by cause of death using the population-attributable fraction and epilepsy-attributable years of potential life lost (YPLL) by age 75 years at ages 15 and over. We updated and undertook a re-review of mortality studies from our previous systematic review following PRISMA guidelines to identify cohort studies of general epilepsy populations reporting a relative risk (RR) of death by cause relative to the background rates in the population. Studies on epilepsy prevalence were identified through published reviews. Country-specific mortality figures were obtained from the WHO World Mortality Database. We performed a pooled analysis with the DerSimonian-Laird random effects method. In countries with very high Human Development Indices, epilepsy contributed to 0.5-1.1 % of all deaths in the total population. Among external causes, suicides (RR 2.9, 95 % confidence interval 2.2-3.8; I(2) 52 %) were the major contributor to YPLL, corresponding to 6.7 % and 4.2 % of excess YPLL due to epilepsy in the United States (US) and in the United Kingdom (UK) in 2010, with 541 (346-792) and 44 (28-65) excess suicide cases, respectively. Fatal accidental falls were more common, with 813 (610-1064) and 95 (71-125) excess deaths in the US and in the UK, but these caused only 2.0 % of excess YPLL as they occurred in older age groups. Suicides were the most important external cause of death in epilepsy patients in terms of excess YPLL, whereas other external causes were either more common in older ages or caused less excess deaths. 10.1007/s10654-015-0095-5