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Neurocritical Care Feb 2022Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage (SAH). However, its efficacy, optimal dosing, and the adverse events associated with levetiracetam prophylaxis remain unclear.
METHODS
A systematic search of PubMed, Embase, and Cochrane central register of controlled trials (CENTRAL) database was conducted from January 1, 2000, to October 30, 2020, including articles addressing treatment with levetiracetam for seizure prophylaxis after SAH, ICH, TBI, and supratentorial neurosurgery. Non-English, pediatric (aged < 18 years), preclinical, reviews, case reports, and articles that included patients with a preexisting seizure condition or epilepsy were excluded. The coprimary meta-analyses examined first seizure events in (1) levetiracetam versus no antiseizure medication and (2) levetiracetam versus other antiseizure medications in all ICH, TBI, SAH, and supratentorial neurosurgery populations. Secondary meta-analyses evaluated the same comparator groups in individual disease populations. Risk of bias in non-randomised studies - of interventions (ROBINS-I) and risk-of-bias tool for randomized trials (RoB-2) tools were used to assess risk of bias.
RESULTS
A total of 30 studies (n = 6 randomized trials, n = 9 prospective studies, and n = 15 retrospective studies), including 7609 patients (n = 4737 with TBI, n = 701 with SAH, n = 261 with ICH, and n = 1910 with neurosurgical diseases) were included in analyses. Twenty-seven of 30 (90%) studies demonstrated moderate to severe risk of bias, and 11 of 30 (37%) studies used low-dosage levetiracetam (250-500 mg twice daily). In the primary meta-analyses, there were no differences in seizure events for levetiracetam prophylaxis (n = 906) versus no antiseizure medication (n = 2728; odds ratio [OR] 0.79, 95% confidence interval [CI] 0.53-1.16, P = 0.23, fixed-effect, I = 26%, P = 0.23 for heterogeneity) or levetiracetam (n = 1950) versus other antiseizure prophylaxis (n = 2289; OR 0.84, 95% CI 0.55-1.28, P = 0.41, random-effects, I = 49%, P = 0.005 for heterogeneity). Only patients with supratentorial neurosurgical diseases benefited from levetiracetam compared with other antiseizure medications (median 0.70 seizure events per-patient-year with levetiracetam versus 2.20 seizure events per-patient-year for other antiseizure medications, OR 0.34, 95% CI 0.20-0.58, P < 0.001, fixed-effects, I = 39%, P = 0.13 for heterogeneity). There were no significant differences in meta-analyses of patients with ICH, SAH, or TBI. Adverse events of any severity were reported in a median of 8% of patients given levetiracetam compared with 21% of patients in comparator groups.
CONCLUSIONS
Based on the current moderately to seriously biased heterogeneous data, which frequently used low and possibly subtherapeutic doses of levetiracetam, our meta-analyses did not demonstrate significant reductions in seizure incidence and neither supports nor refutes the use of levetiracetam prophylaxis in TBI, SAH, or ICH. Levetiracetam may be preferred post supratentorial neurosurgery. More high-quality randomized trials of prophylactic levetiracetam are warranted.
Topics: Adolescent; Anticonvulsants; Child; Humans; Levetiracetam; Prospective Studies; Retrospective Studies; Seizures
PubMed: 34286461
DOI: 10.1007/s12028-021-01296-z -
European Journal of Pediatrics Apr 2021The efficacy of antipyretics for preventing febrile seizure recurrence has been reported by a recent study, and the results might overturn previous evidence. We... (Meta-Analysis)
Meta-Analysis Review
The efficacy of antipyretics for preventing febrile seizure recurrence has been reported by a recent study, and the results might overturn previous evidence. We systematically reviewed the efficacy of antipyretics in the prevention of febrile seizure recurrence in children focused on the timing of its administration. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases for randomized and quasi-randomized trials and prospective non-randomized studies of aged up to 60 months, diagnosed with febrile seizure, who were treated with antipyretics. Data were extracted from eight studies. Only one study reported that antipyretics prevented the recurrence of febrile seizures within the same fever episode (9.1% in the acetaminophen group vs. 23.5% in the control group, p < 0.01). Four studies found no evidence for the efficacy of antipyretics in preventing febrile seizure recurrence in distant fever episodes (odds ratio, 0.92; 95% confidence interval, 0.57-1.48, for two randomized controlled studies).Conclusion: This review provides very limited support for the use of antipyretics in preventing febrile seizure recurrence within the same fever episode and no evidence for its use in distant fever episodes. New studies are required to evaluate this topic further and determine whether the effectiveness of antipyretics is based on intervention timing. What is Known: • Reviews of prophylactic drug management among febrile seizure children found that antipyretics had no significant benefits. • Recent data suggest that antipyretics are effective in preventing febrile seizures. What is New: • Weak evidence suggests a possible role in preventing febrile seizure recurrence within the same fever episode. • There is clearly no role for antipyretic prophylaxis in preventing febrile seizures during distant fever episodes.
Topics: Acetaminophen; Aged; Antipyretics; Child; Humans; Pharmaceutical Preparations; Prospective Studies; Recurrence; Seizures, Febrile
PubMed: 33125519
DOI: 10.1007/s00431-020-03845-8 -
Neurology Apr 2021To 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... (Meta-Analysis)
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 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.
Topics: Drug Resistant Epilepsy; Epilepsies, Partial; Humans; Incidence; Pharmaceutical Preparations; Prevalence; Seizures
PubMed: 33722992
DOI: 10.1212/WNL.0000000000011839 -
BMJ Clinical Evidence Jan 2014Simple febrile seizures are generalised in onset and have a brief duration. The American Academy of Pediatrics defines this brief duration to be <15 minutes; whereas, in... (Review)
Review
INTRODUCTION
Simple febrile seizures are generalised in onset and have a brief duration. The American Academy of Pediatrics defines this brief duration to be <15 minutes; whereas, in the UK, a maximum duration of 10 minutes is used. Simple febrile seizures do not occur more than once in 24 hours and resolve spontaneously. Complex febrile seizures are longer lasting, have focal symptoms (at onset or during the seizure), and can recur within 24 hours or within the same febrile illness. This review only deals with simple febrile seizures. About 2% to 5% of children in the US and Western Europe, and 6% to 9% of infants and children in Japan, will have experienced at least one febrile seizure by the age of 5 years. A very small number of children with simple febrile seizures may develop afebrile seizures, but simple febrile seizures are not associated with any permanent neurological deficits.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments given during episodes of fever in children (aged 6 months to 5 years) with one or more previous simple febrile seizures? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 4 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: intermittent anticonvulsants (clobazam, diazepam, lorazepam), antipyretic drug treatments (paracetamol, ibuprofen), and conservative measures (watchful waiting, physical antipyretic measures [tepid sponging, removing clothes, cooling room, direct fanning of child]).
Topics: Anticonvulsants; Europe; Fever; Humans; Seizures, Febrile
PubMed: 24484859
DOI: No ID Found -
Epilepsy & Behavior : E&B Dec 2021Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a venous line may be difficult in children with seizures which would delay the initiation of treatment. Rectal drug administration can be socially awkward for patients and providers. Intranasal (IN) midazolam offers a valuable substitute that is easier and faster to administer.
OBJECTIVE
To assess the efficacy, safety, and acceptability of intranasal midazolam in children with acute seizure when compared to conventional IV or rectal benzodiazepine (BDZ).
METHODS
PubMed, google scholar, websites clinicaltrials.gov and the WHO-international clinical trials registry platform, were searched. Randomized controlled/prospective randomized trials comparing IN midazolam against IV/rectal BDZ in the treatment of acute seizures in pediatric patients were included in the meta-analysis.
RESULTS
Data of 10 studies were quantitatively analyzed. Intranasal midazolam (n = 169) when compared to IV/rectal BDZ (n = 161) has a shorter interval between hospital arrival and seizure cessation {(mean difference = -3.51; 95% CI [-6.84, -0.18]) P = 0.04}. Regarding time to seizure cessation after midazolam (n = 326) or BDZ (n = 322) administration, there is no significant difference between the two groups {(mean difference = -0.03; 95% CI [-1.30, 1.25]), P = 0.97} and both are equally effective for controlling acute seizures (odds ratio = 1.06; 95% CI [0.43, 2.63]; n = 737).
CONCLUSION
In children with acute seizures, IN midazolam is equally effective in aborting seizure and decreases the total time from hospital arrival and cessation of seizures, eventually leading to faster cessation of seizure as compared to IV/rectal BDZ.
Topics: Administration, Intranasal; Anticonvulsants; Benzodiazepines; Child; Diazepam; Humans; Midazolam; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus
PubMed: 34740090
DOI: 10.1016/j.yebeh.2021.108390 -
The Lancet. Neurology Jul 2017People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of... (Meta-Analysis)
Meta-Analysis Review
Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.
BACKGROUND
People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of life because of the elimination of adverse events. The risk with this action, however, is seizure recurrence. The objectives of our study were to identify predictors of seizure recurrence and long-term seizure outcomes and to produce nomograms for estimation of individualised outcomes.
METHODS
We did a systematic review and meta-analysis, and identified eligible articles and candidate predictors, using PubMed and Embase databases with a last update on Nov 6, 2014. Eligible articles had to report on cohorts of patients with epilepsy who were seizure-free and had started withdrawal of antiepileptic drugs; articles also had to contain information regarding seizure recurrences during and after withdrawal. We excluded surgical cohorts, reports with fewer than 30 patients, and reports on acute symptomatic seizures because these topics were beyond the scope of our objective. Risk of bias was assessed using the Quality in Prognosis Studies system. Data analysis was based on individual participant data. Survival curves and proportional hazards were computed. The strongest predictors were selected with backward selection. Models were converted to nomograms and a web-based tool to determine individual risks.
FINDINGS
We identified 45 studies with 7082 patients; ten studies (22%) with 1769 patients (25%) were included in the meta-analysis. Median follow-up was 5·3 years (IQR 3·0-10·0, maximum 23 years). Prospective and retrospective studies and randomised controlled trials were included, covering non-selected and selected populations of both children and adults. Relapse occurred in 812 (46%) of 1769 patients; 136 (9%) of 1455 for whom data were available had seizures in their last year of follow-up, suggesting enduring seizure control was not regained by this timepoint. Independent predictors of seizure recurrence were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, age at onset of epilepsy, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay, and epileptiform abnormality on electroencephalogram (EEG) before withdrawal. Independent predictors of seizures in the last year of follow-up were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, number of antiepileptic drugs before withdrawal, female sex, family history of epilepsy, number of seizures before remission, focal seizures, and epileptiform abnormality on EEG before withdrawal. Adjusted concordance statistics were 0·65 (95% CI 0·65-0·66) for predicting seizure recurrence and 0·71 (0·70-0·71) for predicting long-term seizure freedom. Validation was stable across the individual study populations.
INTERPRETATION
We present evidence-based nomograms with robust performance across populations of children and adults. The nomograms facilitate prediction of outcomes following drug withdrawal for the individual patient, including both the risk of relapse and the chance of long-term freedom from seizures. The main limitations were the absence of a control group continuing antiepileptic drug treatment and a consistent definition of long-term seizure freedom.
FUNDING
Epilepsiefonds.
Topics: Adult; Anticonvulsants; Child; Humans; Outcome Assessment, Health Care; Recurrence; Remission Induction; Seizures
PubMed: 28483337
DOI: 10.1016/S1474-4422(17)30114-X -
Epilepsia Mar 2022Deep brain stimulation (DBS) is a neuromodulatory treatment used in patients with drug-resistant epilepsy (DRE). The primary goal of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Deep brain stimulation (DBS) is a neuromodulatory treatment used in patients with drug-resistant epilepsy (DRE). The primary goal of this systematic review and meta-analysis is to describe recent advancements in the field of DBS for epilepsy, to compare the results of published trials, and to clarify the clinical utility of DBS in DRE. A systematic literature search was performed by two independent authors. Forty-four articles were included in the meta-analysis (23 for anterior thalamic nucleus [ANT], 8 for centromedian thalamic nucleus [CMT], and 13 for hippocampus) with a total of 527 patients. The mean seizure reduction after stimulation of the ANT, CMT, and hippocampus in our meta-analysis was 60.8%, 73.4%, and 67.8%, respectively. DBS is an effective and safe therapy in patients with DRE. Based on the results of randomized controlled trials and larger clinical series, the best evidence exists for DBS of the anterior thalamic nucleus. Further randomized trials are required to clarify the role of CMT and hippocampal stimulation. Our analysis suggests more efficient deep brain stimulation of ANT for focal seizures, wider use of CMT for generalized seizures, and hippocampal DBS for temporal lobe seizures. Factors associated with clinical outcome after DBS for epilepsy are electrode location, stimulation parameters, type of epilepsy, and longer time of stimulation. Recent advancements in anatomical targeting, functional neuroimaging, responsive neurostimulation, and sensing of local field potentials could potentially lead to improved outcomes after DBS for epilepsy and reduced sudden, unexpected death of patients with epilepsy. Biomarkers are needed for successful patient selection, targeting of electrodes and optimization of stimulation parameters.
Topics: Anterior Thalamic Nuclei; Death, Sudden; Deep Brain Stimulation; Drug Resistant Epilepsy; Epilepsy; Hippocampus; Humans; Intralaminar Thalamic Nuclei; Seizures
PubMed: 34981509
DOI: 10.1111/epi.17157 -
Epilepsia Oct 2023Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed... (Meta-Analysis)
Meta-Analysis
Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.
Topics: Infant, Newborn; Humans; Anticonvulsants; Levetiracetam; Phenytoin; Consensus; Epilepsy; Seizures
PubMed: 37655702
DOI: 10.1111/epi.17745 -
Seizure May 2019To summarize definitions, prevalence, risk factors, consequences, and acute management of seizure clusters using rescue medications.
PURPOSE
To summarize definitions, prevalence, risk factors, consequences, and acute management of seizure clusters using rescue medications.
METHODS
We searched MEDLINE for studies that assessed definitions, clinical characteristics, outcomes, and use of rescue medication for aborting seizure clusters.
RESULTS
Different clinical and statistical definitions for seizure clusters have been proposed, including: ≥3 seizures in 24 h, ≥2 seizures in 24 h, and ≥2 seizures in 6 h. Most studies of seizure clusters have been conducted in tertiary epilepsy centers, with refractory epilepsy patients. Patients with severe and poorly controlled epilepsy are more likely to experience seizure clusters. Seizure clusters can result in increased health care utilization and have negative impact on the quality of life of patients and caregivers. Use of benzodiazepine rescue medications in acute management of seizure clusters can help avoid progression to status epilepticus and reduce emergency room visits. Rescue medications are underutilized in seizure clusters. Currently, rectal diazepam gel is the only FDA approved rescue medication for seizure clusters. In addition, buccal midazolam is approved in European countries for treatment of prolonged seizures. However, various non-rectal non-IV benzodiazepines are safe and effective in treating acute seizures and clusters. Most patients and caregivers preferred non-rectal routes.
CONCLUSION
Identifying patients that are at high risk for seizure clusters, providing them with formal action plans and educating them about use of rescue medication for seizure clusters can help ameliorate the outcomes in this group of epilepsy patients.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Epilepsy; Humans; Infant; Middle Aged; Seizures; Young Adult
PubMed: 29871784
DOI: 10.1016/j.seizure.2018.05.013 -
Epilepsia Apr 2010To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked... (Review)
Review
PURPOSE
To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies.
METHODS
Systematic review of the literature and of epidemiologic studies.
RESULTS
An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs.
DISCUSSION
Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.
Topics: Acute Disease; Cross-Sectional Studies; Diagnosis, Differential; Humans; Seizures
PubMed: 19732133
DOI: 10.1111/j.1528-1167.2009.02285.x