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Epilepsia Apr 2023There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). However, the choice between them is unclear due to lack of head-to-head comparisons. A systematic comparison of neurostimulation outcomes in generalized epilepsy has not been performed previously. The goal of this meta-analysis was to determine whether one of these devices is better than the others to treat generalized epilepsy.
METHODS
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review of PubMed, Embase, and Web of Science was performed for studies reporting seizure outcomes following VNS, RNS, and DBS implantation in generalized drug-resistant epilepsy between the first pivotal trial study for each modality through August 2022. Specific search criteria were used for VNS ("vagus", "vagal", or "VNS" in the title and "epilepsy" or "seizure"), DBS ("deep brain stimulation", "DBS", "anterior thalamic nucleus", "centromedian nucleus", or "thalamic stimulation" in the title and "epilepsy" or "seizure"), and RNS ("responsive neurostimulation" or "RNS" in the title and "epilepsy" or "seizure"). From 4409 articles identified, 319 underwent full-text reviews, and 20 studies were included. Data were pooled using a random-effects model using the meta package in R.
RESULTS
Sufficient data for meta-analysis were available from seven studies for VNS (n = 510) and nine studies for DBS (n = 87). Data from RNS (five studies, n = 18) were insufficient for meta-analysis. The mean (SD) follow-up durations were as follows: VNS, 39.1 (23.4) months; DBS, 23.1 (19.6) months; and RNS, 22.3 (10.6) months. Meta-analysis showed seizure reductions of 48.3% (95% confidence interval [CI] = 38.7%-57.9%) for VNS and 64.8% (95% CI = 54.4%-75.2%) for DBS (p = .02).
SIGNIFICANCE
Our meta-analysis indicates that the use of DBS may lead to greater seizure reduction than VNS in generalized epilepsy. Results from RNS use are promising, but further research is required.
Topics: Humans; Epilepsy; Drug Resistant Epilepsy; Seizures; Epilepsy, Generalized; Vagus Nerve Stimulation; Anterior Thalamic Nuclei; Treatment Outcome
PubMed: 36727550
DOI: 10.1111/epi.17524 -
Pharmacopsychiatry Jul 2018This paper is a systematic review on seizures under treatment with substances licensed for major depression. (Review)
Review
OBJECTIVE
This paper is a systematic review on seizures under treatment with substances licensed for major depression.
METHOD
Systematic review protocol is available in PROSPERO registration number CRD42016034010. Twenty-five substances were selected according to frequencies of prescriptions and publications. A PubMed search was conducted with "substance name" and "seizure."
RESULTS
A total of 2291 articles were screened, out of which 164 fulfilled inclusion criteria. Data synthesis was possible only to a limited extent due to heterogeneity of included patients, observation periods, methods, and outcomes. Evidence for an at most moderate, but still low, risk (>0.1% under regular doses) was found highest for clomipramine, followed by quetiapine, amitriptyline, venlafaxine, citalopram, sertraline, trazodone, mirtazapine, paroxetine, bupropion, and escitalopram. For fluoxetine and duloxetine, the risk seems to be negligible. For the other, mostly newer, substances, sufficient evidence was not available. An increased risk for lithium, as reported in many reviews and textbooks, could not be confirmed.
CONCLUSIONS
Antidepressive treatment is rather safe in terms of risk of seizures and also can be generally recommended in the treatment of patients with epilepsy.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; PubMed; Seizures
PubMed: 28850959
DOI: 10.1055/s-0043-117962 -
Seizure Nov 2022Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.
METHODS
All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.
RESULTS
Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.
CONCLUSIONS
Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.
Topics: Adult; Child; Humans; Anticonvulsants; Benzodiazepines; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Seizures; Status Epilepticus; Valproic Acid; Drug Resistance; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36209676
DOI: 10.1016/j.seizure.2022.09.017 -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8 -
Epilepsia Nov 2023We conducted a systematic review and meta-analysis to evaluate postoperative seizure and memory outcomes of temporal lobe epilepsy with different hippocampal sclerosis... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to evaluate postoperative seizure and memory outcomes of temporal lobe epilepsy with different hippocampal sclerosis (HS) subtypes classified by International League Against Epilepsy (ILAE) Consensus Guidelines in 2013. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Library from January 1, 2013 to August 6, 2023. Observational studies reporting seizure and memory outcomes among different HS subtypes were included. We used the Newcastle-Ottawa scale to assess the risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the quality of evidence. Seizure freedom and improved outcome (Engel 1 or ILAE class 1-2) ≥1 year after surgery were defined as the primary and secondary seizure outcome. A random-effects meta-analysis by DerSimonian and Laird method was performed to obtain pooled risk ratio (RRs) with 95% confidence interval (CIs). The memory impairment was narratively reviewed because of various evaluation tools. Fifteen cohort studies with 2485 patients were eligible for the meta-analysis of seizure outcome. Six cohorts with detailed information on postoperative memory outcome were included. The pooled RRs of seizure freedom, with moderate to substantial heterogeneity, were .98 (95% CI = .84-1.15) between HS type 2 and type 1, 1.11 (95% CI = .82-1.52) between type 3 and type 1, and .80 (95% CI = .62-1.03) between the no-HS and HS groups. No significant difference of improved outcome was found between different subtypes (p > .05). The quality of evidence was deemed to be low to very low according to GRADE. The long-term seizure outcome (≥5 years after surgery) and memory impairment remained controversial.
Topics: Humans; Epilepsy, Temporal Lobe; Hippocampal Sclerosis; Hippocampus; Sclerosis; Seizures; Epilepsy; Memory Disorders
PubMed: 37611927
DOI: 10.1111/epi.17757 -
Journal of Medical Virology Jan 2017Human herpesvirus-6 (HHV-6) is a common infection in childhood. This systematic review aims to assess the relationship between HHV-6 infection and seizure disorders... (Meta-Analysis)
Meta-Analysis Review
Human herpesvirus-6 (HHV-6) is a common infection in childhood. This systematic review aims to assess the relationship between HHV-6 infection and seizure disorders based on available literature. MEDLINE database was searched using a search strategy. We included studies that were published after 1993 in English, and described patients with HHV-6 infection and accompanying seizure or status epilepticus. We identified 503 articles, and included 147 studies. Meta-analysis results showed a 0.21 detection rate of HHV-6 in febrile seizure patients. In the febrile seizure group (110 cases), 76 patients had simple and 34 had complex febrile seizures. Patients with "HHV-6 infection and status epilepticus" had a mean age of 16.24 months. In children with febrile illnesses, a higher index of clinical suspicion for HHV-6 infection may be required. Further studies including CSF and brain tissue may be needed to validate relationships between HHV6 infection and epilepsy. J. Med. Virol. 89:161-169, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Herpesvirus 6, Human; Humans; Roseolovirus Infections; Seizures
PubMed: 27272972
DOI: 10.1002/jmv.24594 -
JAMA Neurology Nov 2023Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the authors' knowledge.
OBJECTIVE
To investigate outcomes in people with PSS compared with people without PSS.
DATA SOURCES
MEDLINE, Embase, PsycInfo, Cochrane, LILACS, LIPECS, and Web of Science, with years searched from 1951 to January 30, 2023.
STUDY SELECTION
Observational studies that reported PSS outcomes.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used for abstracting data, and the Joanna Briggs Institute tool was used for risk-of-bias assessment. Data were reported as odds ratio (OR) and standardized mean difference (SMD) with a 95% CI using a random-effects meta-analysis. Publication bias was assessed using funnel plots and the Egger test. Outlier and meta-regression analyses were performed to explore the source of heterogeneity. Data were analyzed from November 2022 to January 2023.
MAIN OUTCOMES AND MEASURES
Measured outcomes were mortality, poor functional outcome (modified Rankin scale [mRS] score 3-6), disability (mean mRS score), recurrent stroke, and dementia at patient follow-up.
RESULTS
The search yielded 71 eligible articles, including 20 110 patients with PSS and 1 166 085 patients without PSS. Of the participants with PSS, 1967 (9.8%) had early seizures, and 10 605 (52.7%) had late seizures. The risk of bias was high in 5 studies (7.0%), moderate in 35 (49.3%), and low in 31 (43.7%). PSSs were associated with mortality risk (OR, 2.1; 95% CI, 1.8-2.4), poor functional outcome (OR, 2.2; 95% CI, 1.8-2.8), greater disability (SMD, 0.6; 95% CI, 0.4-0.7), and increased dementia risk (OR, 3.1; 95% CI, 1.3-7.7) compared with patients without PSS. In subgroup analyses, early seizures but not late seizures were associated with mortality (OR, 2.4; 95% CI, 1.9-2.9 vs OR, 1.2; 95% CI, 0.8-2.0) and both ischemic and hemorrhagic stroke subtypes were associated with mortality (OR, 2.2; 95% CI, 1.8-2.7 vs OR, 1.4; 95% CI, 1.0-1.8). In addition, early and late seizures (OR, 2.4; 95% CI, 1.6-3.4 vs OR, 2.7; 95% CI, 1.8-4.1) and stroke subtypes were associated with poor outcomes (OR, 2.6; 95% CI, 1.9-3.7 vs OR, 1.9; 95% CI, 1.0-3.6).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that PSSs were associated with significantly increased mortality and severe disability in patients with history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.
Topics: Humans; Stroke; Seizures; Outcome Assessment, Health Care; Dementia
PubMed: 37721736
DOI: 10.1001/jamaneurol.2023.3240 -
The Cochrane Database of Systematic... Jan 2023Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates, to guide clinical practice on the risks of developing further unprovoked seizures (and by definition, a diagnosis of epilepsy) following single unprovoked epileptic seizure.
OBJECTIVES
1. To provide an accurate estimate of the proportion of individuals going on to have further unprovoked seizures at subsequent time points following a single unprovoked epileptic seizure (or cluster of epileptic seizures within a 24-hour period, or a first episode of status epilepticus), of any seizure type (overall prognosis). 2. To evaluate the mortality rate following a first unprovoked epileptic seizure.
SEARCH METHODS
We searched the following databases on 19 September 2019 and again on 30 March 2021, with no language restrictions. The Cochrane Register of Studies (CRS Web), MEDLINE Ovid (1946 to March 29, 2021), SCOPUS (1823 onwards), ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. In MEDLINE (Ovid) the coverage end date always lags a few days behind the search date.
SELECTION CRITERIA
We included studies, both retrospective and prospective, of all age groups (except those in the neonatal period (< 1 month of age)), of people with a single unprovoked seizure, followed up for a minimum of six months, with no upper limit of follow-up, with the study end point being seizure recurrence, death, or loss to follow-up. To be included, studies must have included at least 30 participants. We excluded studies that involved people with seizures that occur as a result of an acute precipitant or provoking factor, or in close temporal proximity to an acute neurological insult, since these are not considered epileptic in aetiology (acute symptomatic seizures). We also excluded people with situational seizures, such as febrile convulsions.
DATA COLLECTION AND ANALYSIS
Two review authors conducted the initial screening of titles and abstracts identified through the electronic searches, and removed non-relevant articles. We obtained the full-text articles of all remaining potentially relevant studies, or those whose relevance could not be determined from the abstract alone and two authors independently assessed for eligibility. All disagreements were resolved through discussion with no need to defer to a third review author. We extracted data from included studies using a data extraction form based on the checklist for critical appraisal and data extraction for systematicreviews of prediction modelling studies (CHARMS). Two review authors then appraised the included studies, using a standardised approach based on the quality in prognostic studies (QUIPS) tool, which was adapted for overall prognosis (seizure recurrence). We conducted a meta-analysis using Review Manager 2014, with a random-effects generic inverse variance meta-analysis model, which accounted for any between-study heterogeneity in the prognostic effect. We then summarised the meta-analysis by the pooled estimate (the average prognostic factor effect), its 95% confidence interval (CI), the estimates of I² and Tau² (heterogeneity), and a 95% prediction interval for the prognostic effect in a single population at three various time points, 6 months, 12 months and 24 months. Subgroup analysis was performed according to the ages of the cohorts included; studies involving all ages, studies that recruited adult only and those that were purely paediatric.
MAIN RESULTS
Fifty-eight studies (involving 54 cohorts), with a total of 12,160 participants (median 147, range 31 to 1443), met the inclusion criteria for the review. Of the 58 studies, 26 studies were paediatric studies, 16 were adult and the remaining 16 studies were a combination of paediatric and adult populations. Most included studies had a cohort study design with two case-control studies and one nested case-control study. Thirty-two studies (29 cohorts) reported a prospective longitudinal design whilst 15 studies had a retrospective design whilst the remaining studies were randomised controlled trials. Nine of the studies included presented mortality data following a first unprovoked seizure. For a mortality study to be included, a proportional mortality ratio (PMR) or a standardised mortality ratio (SMR) had to be given at a specific time point following a first unprovoked seizure. To be included in the meta-analysis a study had to present clear seizure recurrence data at 6 months, 12 months or 24 months. Forty-six studies were included in the meta-analysis, of which 23 were paediatric, 13 were adult, and 10 were a combination of paediatric and adult populations. A meta-analysis was performed at three time points; six months, one year and two years for all ages combined, paediatric and adult studies, respectively. We found an estimated overall seizure recurrence of all included studies at six months of 27% (95% CI 24% to 31%), 36% (95% CI 33% to 40%) at one year and 43% (95% CI 37% to 44%) at two years, with slightly lower estimates for adult subgroup analysis and slightly higher estimates for paediatric subgroup analysis. It was not possible to provide a summary estimate of the risk of seizure recurrence beyond these time points as most of the included studies were of short follow-up and too few studies presented recurrence rates at a single time point beyond two years. The evidence presented was found to be of moderate certainty.
AUTHORS' CONCLUSIONS
Despite the limitations of the data (moderate-certainty of evidence), mainly relating to clinical and methodological heterogeneity we have provided summary estimates for the likely risk of seizure recurrence at six months, one year and two years for both children and adults. This provides information that is likely to be useful for the clinician counselling patients (or their parents) on the probable risk of further seizures in the short-term whilst acknowledging the paucity of long-term recurrence data, particularly beyond 10 years.
Topics: Adult; Child; Humans; Anticonvulsants; Case-Control Studies; Cohort Studies; Epilepsies, Partial; Epilepsy; Prognosis; Prospective Studies; Retrospective Studies; Seizures
PubMed: 36688481
DOI: 10.1002/14651858.CD013847.pub2 -
The Turkish Journal of Pediatrics 2020Zinc has been reported to be low in children with febrile seizure compared to febrile cases without seizures, but results are inconsistent. A meta-analysis was performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Zinc has been reported to be low in children with febrile seizure compared to febrile cases without seizures, but results are inconsistent. A meta-analysis was performed to systematically evaluate the serum level of zinc in febrile children aged between 6-72 months with or without seizures.
MATERIAL AND METHODS
A systematic search of databases was performed from January 2000 to January 2019. Studies comparing the serum level of zinc in febrile children with or without seizure were selected.
RESULTS
The major outcome was serum level of zinc. Random effect model was used to calculate pooled standardized mean differences (SMD) with 95% confidence intervals (CIs). A total of 31 articles were included. Meta-analysis suggested that the serum level of zinc is lower in patients with febrile seizure versus febrile cases without seizure (SMD: -1.2, 95%CI= (-1.47, -0.93). In subgroup and sensitivity analysis no significant change was observed in pooled SMD. In meta-regression analysis sample size as a continuous variable had a significant influence on between-study variance (p= 0.02). According to cumulative analysis the difference of serum level of zinc in febrile children with or without seizure decreased with time.
CONCLUSION
This meta-result indicated a significant association of zinc deficiency with seizure in febrile children. It is suspected that decreased level of zinc may be involved in seizure occurrences and it may play a role in the pathogenesis of febrile seizure.
Topics: Child; Child, Preschool; Fever; Humans; Infant; Malnutrition; Seizures; Seizures, Febrile; Zinc
PubMed: 32558408
DOI: 10.24953/turkjped.2020.03.001 -
European Journal of Neurology Feb 2022New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active... (Review)
Review
BACKGROUND AND PURPOSE
New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions.
METHODS
A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome.
RESULTS
Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case-control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called 'cryptogenic NORSE'. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described.
CONCLUSIONS
Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE.
Topics: Adult; Child; Drug Resistant Epilepsy; Encephalitis; Epileptic Syndromes; Humans; Retrospective Studies; Status Epilepticus
PubMed: 34661330
DOI: 10.1111/ene.15149