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Epilepsia Jan 2016The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using... (Review)
Review
OBJECTIVE
The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development.
METHODS
A systematic review of the literature (1985-2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology [AAN], ILAE) were also searched to minimize publication bias. Two independent reviewers screened abstracts, reviewed full text articles, and performed data abstraction. Descriptive statistics and a meta-analysis were generated.
RESULTS
The search identified 10,926 abstracts. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug-resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1-7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 ± 1.05 [SD]).
SIGNIFICANCE
We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future epilepsy-related guidelines.
Topics: Advisory Committees; Databases, Factual; Epilepsy; Evidence-Based Medicine; Humans; Practice Guidelines as Topic; Societies, Medical
PubMed: 26659723
DOI: 10.1111/epi.13273 -
JAMA Network Open Apr 2023Epilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Epilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with several different adverse events (AEs).
OBJECTIVE
To investigate the frequency and risk of AEs developing in patients with epilepsy who are using CBD.
DATA SOURCES
PubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published from database inception up to August 4, 2022. The search strategy included a combination of the following keywords: (cannabidiol OR epidiolex) AND (epilepsy OR seizures).
STUDY SELECTION
The review included all randomized clinical trials that investigated at least 1 AE from the use of CBD in patients with epilepsy.
DATA EXTRACTION AND SYNTHESIS
Basic information about each study was extracted. I2 statistics were calculated using Q statistics to assess the statistical heterogeneity among the included studies. A random-effects model was used in cases of substantial heterogeneity, and a fixed-effects model was used if the I2 statistic for the AEs was lower than 40%. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.
MAIN OUTCOMES AND MEASURES
Frequency of each AE and risk of developing each AE in patients with epilepsy using CBD.
RESULTS
Nine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs. The overall risk ratios (RRs) for any grade and severe grade AEs were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively, for the CBD group compared with the control group. Compared with the control group, the CBD group had a greater risk for incidence of serious AEs (RR, 2.67; 95% CI, 1.83-3.88), AEs resulting in discontinuation (RR, 3.95; 95% CI, 1.86-8.37), and AEs resulting in dose reduction (RR, 9.87; 95% CI, 5.34-14.40). Because most of the included studies had some risk of bias (3 raised some concerns and 3 were at high risk of bias), these findings should be interpreted with some caution.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several AEs. Additional studies are needed to determine the safe and effective CBD dosage for treating epilepsy.
Topics: Humans; Cannabidiol; Epilepsy; Seizures; Bias
PubMed: 37079302
DOI: 10.1001/jamanetworkopen.2023.9126 -
PLoS Neglected Tropical Diseases Mar 2017We reviewed studies that analyzed cysticercosis (CC), neurocysticercosis (NCC) and epilepsy across Latin America, Asia and Sub-Saharan Africa, to estimate the odds ratio... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We reviewed studies that analyzed cysticercosis (CC), neurocysticercosis (NCC) and epilepsy across Latin America, Asia and Sub-Saharan Africa, to estimate the odds ratio and etiologic fraction of epilepsy due to CC in tropical regions.
METHODOLOGY
We conducted a systematic review of the literature on cysticercosis and epilepsy in the tropics, collecting data from case-control and cross-sectional studies. Exposure criteria for CC included one or more of the following: serum ELISA or EITB positivity, presence of subcutaneous cysts (both not verified and unverified by histology), histology consistent with calcified cysts, and brain CT scan consistent with NCC. A common odds-ratio was then estimated using meta-analysis.
PRINCIPAL FINDINGS
37 studies from 23 countries were included (n = 24,646 subjects, 14,934 with epilepsy and 9,712 without epilepsy). Of these, 29 were case-control (14 matched). The association between CC and epilepsy was significant in 19 scientific articles. Odds ratios ranged from 0.2 to 25.4 (a posteriori power 4.5-100%) and the common odds ratio was 2.7 (95% CI 2.1-3.6, p <0.001). Three subgroup analyses performed gave odds ratios as: 2.2 (EITB-based studies), 3.2 (CT-based studies), 1.9 (neurologist-confirmed epilepsy; door-to-door survey and at least one matched control per case). Etiologic fraction was estimated to be 63% in the exposed group among the population.
SIGNIFICANCE
Despite differences in findings, this meta-analysis suggests that cysticercosis is a significant contributor to late-onset epilepsy in tropical regions around the world, and its impact may vary depending on transmission intensity.
Topics: Africa South of the Sahara; Asia; Case-Control Studies; Cross-Sectional Studies; Cysticercosis; Epilepsy; Humans; Latin America
PubMed: 28267746
DOI: 10.1371/journal.pntd.0005153 -
Epilepsia Nov 2016Quality and safety in epilepsy monitoring units (EMUs) are of great importance because patients' seizures are induced rather than prevented in this hospital setting.... (Review)
Review
OBJECTIVE
Quality and safety in epilepsy monitoring units (EMUs) are of great importance because patients' seizures are induced rather than prevented in this hospital setting. However, the measurement and evaluation of quality and safety in EMUs are heterogeneous, as are practices and processes of care. To improve the measurement of quality and safety in EMUs, we sought to develop evidence-based and consensus-driven quality indicators, adhering to previously described methodologic standards.
METHODS
Candidate quality indicators were identified using a recent systematic review on quality and safety indicators in EMUs. These were supplemented by expert opinion to identify other indicators that had not been reported previously. The candidate quality indicators were then evaluated using a modified Delphi technique among a multidisciplinary EMU quality improvement team. Candidate indicators identified as important and feasible through the Delphi technique were then developed into quality metrics.
RESULTS
Thirty-four candidate indicators were abstracted from 135 studies included in the earlier systematic review, and two additional candidate indicators were suggested through consensus from experts. Consensus was reached after two modified Delphi rounds for 25 quality indicators identified as important. These 25 indicators were then developed into quality metrics using a standardized data collection form and were deployed in an online database for systematic data capture and further analyses.
SIGNIFICANCE
These quality indicators have the potential to improve the reporting of quality and safety in EMUs through standardized measurement and evaluation of the quality and safety of care. The ultimate goal is improved patient care and clinical outcomes through safer and better care for people with epilepsy in the EMU.
Topics: Adult; Aged; Aged, 80 and over; Consensus; Delphi Technique; Electroencephalography; Epilepsy; Humans; Middle Aged; Monitoring, Physiologic
PubMed: 27723937
DOI: 10.1111/epi.13563 -
Epilepsia Nov 2016The epilepsy monitoring unit (EMU) is a valuable resource for optimizing management of persons with epilepsy, but may place patients at risk for adverse events due to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The epilepsy monitoring unit (EMU) is a valuable resource for optimizing management of persons with epilepsy, but may place patients at risk for adverse events due to withdrawal of treatment and induction of symptoms. The purpose of this study was to synthesize data on the safety and quality of care in EMUs to inform the development of quality indicators for EMUs.
METHODS
A systematic review was conducted according to the Preferred Reporting and Items for Systematic Review and Meta-Analysis (PRISMA) statement. The search strategy, which included broad search terms and synonyms pertaining to the EMU, was run in six medical databases and included conference proceedings. Data abstracted included patient and EMU demographics and quality and safety variables. Study quality was evaluated using a modified 15-item Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Descriptive statistics and meta-analyses were used to describe and synthesize the evidence.
RESULTS
The search yielded 7,601 references, of which 604 were reviewed in full text. One-hundred thirty-five studies were included. The quality and safety data came from 181,823 patients and reported on 34 different quality and safety variables. Included studies commonly reported the number of patients (108 studies; median number patients, 171.5), age (49 studies; mean age 35.7 years old), and the reason for admission (34 studies). The most common quality and safety data reported were the utility of the EMU admission (38 studies). Thirty-three studies (24.4%) reported on adverse events, and yielded a pooled proportion of adverse events of 7% (95% confidence interval [CI] 5-9%). The mean quality score was 73.3% (standard deviation [SD] 17.2).
SIGNIFICANCE
This study demonstrates that there is a great deal of variation in the reporting of quality and safety measures and in the quality and safety in EMUs. Study quality also varied considerably from one study to the next. These findings highlight the need to develop evidence-based, consensus-driven quality indicators for EMUs.
Topics: Electroencephalography; Epilepsy; Humans; Monitoring, Physiologic
PubMed: 27714792
DOI: 10.1111/epi.13564 -
The Cochrane Database of Systematic... Jan 2018Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled by a single antiepileptic drug (AED) and they usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6) and updated in 2015.
OBJECTIVES
To investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy.
SEARCH METHODS
For the latest update on 9 February 2017, we searched the Cochrane Epilepsy Specialized Register, CENTRAL and MEDLINE . We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions.
SELECTION CRITERIA
Randomized controlled, add-on trials comparing losigamone with placebo for focal epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing).
MAIN RESULTS
Two trials involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one trial as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72), but associated with a significant increase of treatment withdrawal when compared with those taking placebo (RR 2.16, 95% CI 1.28 to 3.67). For the safety outcomes, results indicated that the proportion of participants who experienced adverse events in the losigamone group was higher than in the placebo group (RR 1.34, 95% CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64). The proportion of participants achieving seizure freedom was not reported in either trial report. A subgroup analysis according to different doses of losigamone showed that a higher dose of losigamone (1500 mg/day) was associated with a greater reduction in seizure frequency than lower doses, but was also associated with more dropouts due to adverse events.
AUTHORS' CONCLUSIONS
The results of this review showed that losigamone did reduce seizure frequency but was associated with more treatment withdrawals when used as an add-on therapy for people with focal epilepsy. However, the included trials were of short-term duration and uncertain quality. Future well-designed randomized, double-blind, placebo-controlled trials with a longer-term duration are needed. No new studies have been found since the last version of this review. We judged the overall quality of the evidence for the outcomes assessed as moderate.
Topics: Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Epilepsies, Partial; Furans; Humans; Middle Aged; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 29355908
DOI: 10.1002/14651858.CD009324.pub4 -
The Cochrane Database of Systematic... Mar 2022This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30%... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30% of individuals with epilepsy continue to have epileptic seizures despite treatment with an antiepileptic drug. These patients are classified as drug-resistant and require treatment with a combination of multiple antiepileptic drugs. Brivaracetam is a third-generation antiepileptic drug that is a high-affinity ligand for synaptic vesicle protein 2A. In this review we investigated the use of brivaracetam as add-on therapy for epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of brivaracetam when used as add-on treatment for people with drug-resistant epilepsy.
SEARCH METHODS
For the latest update we searched the following databases on 7 September 2021: the Cochrane Register of Studies (CRS Web); MEDLINE (Ovid) 1946 to 3 September 2021. CRS Web includes randomised controlled trials (RCTs) and quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.
SELECTION CRITERIA
We searched for parallel-group RCTs that recruited people of any age with drug-resistant epilepsy. We accepted studies with any level of blinding (double-blind, single-blind, or unblinded).
DATA COLLECTION AND ANALYSIS
In accordance with standard Cochrane methodological procedures, two review authors independently assessed trials for inclusion before evaluating trial quality and extracting relevant data. The primary outcome to be assessed was 50% or greater reduction in seizure frequency. Secondary outcomes were: seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse events, the proportion of participants who experienced any adverse events, and drug interactions. We used an intention-to-treat population for all primary analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
We did not identify any new studies for this update, therefore the results and conclusions of the review are unchanged. The previous review included six studies involving a total of 2411 participants. Only one study included participants with both focal and generalised onset seizures; the other five trials included participants with focal onset seizures only. Study participants were aged 16 to 80 years. Treatment periods ranged from 7 to 16 weeks. We judged two studies to have low risk of bias and four to have unclear risk of bias. Details on the method used for allocation concealment and how blinding was maintained were insufficient in one study each. One study did not report all outcomes prespecified in the trial protocol, and there were discrepancies in reporting in a further study. Participants receiving brivaracetam add-on were more likely to experience a 50% or greater reduction in seizure frequency than those receiving placebo (RR 1.81, 95% CI 1.53 to 2.14; 6 studies; moderate-certainty evidence). Participants receiving brivaracetam were more likely to attain seizure freedom; however, the evidence is of low certainty (RR 5.89, 95% CI 2.30 to 15.13; 6 studies). The incidence of treatment withdrawal for any reason was slightly greater for participants receiving brivaracetam compared to those receiving placebo (RR 1.27, 95% CI 0.94 to 1.74; 6 studies; low-certainty evidence). The risk of participants experiencing one or more adverse events did not differ significantly following treatment with brivaracetam compared to placebo (RR 1.08, 95% CI 1.00 to 1.17; 5 studies; moderate-certainty evidence). However, participants receiving brivaracetam did appear to be more likely to withdraw from treatment due to adverse events compared with those receiving placebo (RR 1.54, 95% CI 1.02 to 2.33; 6 studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
When used as add-on therapy for individuals with drug-resistant epilepsy, brivaracetam may be effective in reducing seizure frequency and may aid patients in achieving seizure freedom. However, add-on brivaracetam is probably associated with a greater proportion of treatment withdrawals due to adverse events compared with placebo. It is important to note that only one of the eligible studies included participants with generalised epilepsy. None of the included studies involved participants under the age of 16, and all studies were of short duration. Consequently, the findings of this review are mainly applicable to adult patients with drug-resistant focal epilepsy. Future research should focus on investigating the tolerability and efficacy of brivaracetam during longer-term follow-up, as well as assess the efficacy and tolerability of add-on brivaracetam in managing other types of seizures and in other age groups.
Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsy, Generalized; Humans; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures
PubMed: 35285519
DOI: 10.1002/14651858.CD011501.pub3 -
Epilepsia Mar 2016Stereo-electroencephalography (SEEG) is a procedure performed for patients with intractable epilepsy in order to anatomically define the epileptogenic zone (EZ) and the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Stereo-electroencephalography (SEEG) is a procedure performed for patients with intractable epilepsy in order to anatomically define the epileptogenic zone (EZ) and the possible related functional cortical areas. By avoiding the need for large craniotomies and due to its intrinsic precision placement features, SEEG may be associated with fewer complications. Nevertheless, intracerebral electrodes have gained a reputation of excessive invasiveness, with a "relatively high morbidity" associated with their placement. A systematic literature review and meta-analysis of SEEG complications has not been previously performed. The goal of this study is to quantitatively review the incidence of various surgical complications associated with SEEG electrode implantation in the literature and to provide a summary estimate. This will allow physicians to accurately counsel their patients about the potential complications related to this method of extraoperative invasive monitoring.
METHODS
The systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted MEDLINE, Scopus, and Web of Science database searches with the search algorithm. We analyzed complication rates using a fixed-effects model with inverse variance weighting. Calculations for the meta-analysis and construction of forest plots were completed using an established spreadsheet. The principal summary measures were the effect summary value and 95% confidence intervals (CIs).
RESULTS
The initial 1,901 retrieved citations were reviewed. After removing 787 duplicates, the titles and abstracts of 1,114 publications were screened. At this stage, studies that did not mention the absence or presence of complications following SEEG or that did not fulfill the inclusion criteria in any manner were excluded. After excluding 1,057 citations, the full text was assessed in the resulting 57 articles for eligibility criteria. The most common complications were hemorrhagic (pooled prevalence 1.0%, 95% confidence interval [CI] 0.6-1.4%) or infectious (pooled prevalence 0.8%, 95% CI 0.3-1.2%). Five mortalities were identified (pooled prevalence 0.3%, 95% CI -0.1-0.6%). Overall, our analysis identified 121 surgical complications related to SEEG insertion and monitoring (pooled prevalence 1.3%, 95% CI 0.9-1.7%).
SIGNIFICANCE
This review represents a comprehensive estimation of the actual incidence of complications related to SEEG. We report a rate substantially lower than the complication rates reported for other methods of extraoperative invasive monitoring. These data should alleviate the concerns of some regarding the safety of the "stereotactic" method, allowing a better decision process among the different methods of invasive monitoring and ameliorating the fear associated with the placement of depth electrodes.
Topics: Electroencephalography; Epilepsy; Humans; Postoperative Complications; Stereotaxic Techniques
PubMed: 26899389
DOI: 10.1111/epi.13298 -
The Cochrane Database of Systematic... Nov 2015This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 1).The efficacy and safety of vigabatrin (VGB) as an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 1).The efficacy and safety of vigabatrin (VGB) as an add-on therapy for refractory epilepsy have been well established. However, this information needs to be weighed against the risk of development of visual field defects. Whether VGB monotherapy is an effective and safe treatment compared with the standard antiepileptic drug carbamazepine (CBZ) as monotherapy for epilepsy has not been systematically reviewed.
OBJECTIVES
To investigate the efficacy and safety of VGB versus CBZ monotherapy for epilepsy in children and adults.
SEARCH METHODS
For the latest update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3 of 4), MEDLINE (1948 to July 2015), EMBASE (1974 to July 2015) and the Chinese Biomedical Database (CBM) (1979 to July 2015). We searched trial registers and contacted the manufacturer of VGB and authors of included studies for additional information. We applied no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing VGB versus CBZ monotherapy for epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. The primary outcome was time to treatment withdrawal. Secondary outcomes were time to achieve six-month and 12-month remission after randomisation, time to first seizure after randomisation and adverse events. We presented results as hazard ratios (HRs) with 95% confidence intervals (CIs) (time to event data) or as risk ratios (RRs) with 95% CIs (adverse events).
MAIN RESULTS
Five studies involving a total of 734 participants were eligible for inclusion. We assessed only one study as good quality and the other four as poor quality. However, it was difficult to perform a meta-analysis by extracting aggregate data to synthesise the results as originally planned, mainly because not all studies reported the same outcomes as those chosen for this review. No significant differences favoured VGB or CBZ in terms of time to treatment withdrawal and time to achieve six-month remission after dose stabilisation from randomisation, but results did show a disadvantage for VGB on time to first seizure after randomisation. Compared with CBZ, VGB was associated with more occurrences of weight gain and fewer occurrences of skin rash and drowsiness. No differences in visual field defects and visual disturbances were noted.
AUTHORS' CONCLUSIONS
Data are currently insufficient to address the risk-benefit balance of VGB versus CBZ monotherapy for epilepsy. Given the high prevalence of visual field defects reported in an existing systematic review of observational studies (Maguire 2010), VGB monotherapy should be prescribed with caution for epilepsy and should not be considered a first-line choice. If necessary, the visual field should be frequently assessed. Future research should focus on investigating the reasons for visual field defects and exploring potential prevention strategies. Moreover, future monotherapy studies of epilepsy should report results according to the recommendations of the International League Against Epilepsy (ILAE) Commission, and methodological quality should be improved.
Topics: Anticonvulsants; Carbamazepine; Epilepsy; Humans; Randomized Controlled Trials as Topic; Risk Assessment; Vigabatrin
PubMed: 26580100
DOI: 10.1002/14651858.CD008781.pub3 -
Neurology Jan 2023Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a...
BACKGROUND AND OBJECTIVES
Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms.
METHODS
We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months.
RESULTS
Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported.
DISCUSSION
Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life.
TRIAL REGISTRATION INFORMATION
This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.
Topics: Infant; Infant, Newborn; Child; Humans; Lamotrigine; Levetiracetam; Topiramate; Spasms, Infantile; Quality of Life; Epilepsy; Anticonvulsants; Diet, Ketogenic
PubMed: 36270899
DOI: 10.1212/WNL.0000000000201026