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Epilepsia Jan 2021Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Clinical genetic sequencing is frequently utilized to diagnose individuals with neurodevelopmental disorders (NDDs). Here we perform a meta-analysis and systematic review of the success rate (diagnostic yield) of clinical sequencing through next-generation sequencing (NGS) across NDDs. We compare the genetic testing yield across NDD subtypes and sequencing technology.
METHODS
We performed a systematic review of the PubMed literature until May 2020. We included clinical sequencing studies that utilized NGS in individuals with epilepsy, autism spectrum disorder (ASD), or intellectual disability (ID). Data were extracted, reviewed, and categorized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two investigators performed clinical evaluation and grouping following the International League Against Epilepsy (ILAE) guidelines. Pooled rates of the diagnostic yield and 95% confidence intervals were estimated with a random-effects model.
RESULTS
We identified 103 studies (epilepsy, N = 72; ASD, N = 14; ID, N = 21) across 32,331 individuals. Targeted gene panel sequencing was used in 73, and exome sequencing in 36 cohorts. Given highly selected patient cohorts, the diagnostic yield was 17.1% for ASD, 24% for epilepsy, and 28.2% for ID (23.7% overall). The highest diagnostic yield for epilepsy subtypes was observed in individuals with ID (27.9%) and early onset seizures (36.8%). The diagnostic yield for exome sequencing was higher than for panel sequencing, even though not statistically significant (27.2% vs 22.6%, P = .071). We observed that clinical sequencing studies are performed predominantly in countries with a high Inequality-adjusted Human Development Index (IHDI) (countries with sequencing studies: IHDI median = 0.84, interquartile range [IQR] = 0.09 vs countries without sequencing studies: IHDI median = 0.56, IQR = 0.3). No studies from Africa, India, or Latin America were identified, indicating potential barriers to genetic testing.
SIGNIFICANCE
This meta-analysis and systematic review provides a comprehensive overview of clinical sequencing studies of NDDs and will help guide policymaking and steer decision-making in patient management.
Topics: Age of Onset; Autism Spectrum Disorder; Epilepsy; High-Throughput Nucleotide Sequencing; Humans; Intellectual Disability; Sequence Analysis, DNA; Exome Sequencing
PubMed: 33200402
DOI: 10.1111/epi.16755 -
JAMA Pediatrics Mar 2023Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.
OBJECTIVE
To evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.
DATA SOURCES
Systematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.
STUDY SELECTION
Randomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.
DATA EXTRACTION AND SYNTHESIS
Data extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve.
MAIN OUTCOMES AND MEASURES
Short-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes.
RESULTS
Of 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event-related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes.
CONCLUSIONS AND RELEVANCE
This study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.
Topics: Child; Humans; Drug Resistant Epilepsy; Network Meta-Analysis; Diet, Ketogenic; Seizures; Diet, High-Protein Low-Carbohydrate; Treatment Outcome
PubMed: 36716045
DOI: 10.1001/jamapediatrics.2022.5648 -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Apr 2022This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, eventrate, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
For the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'. We performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting. Results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA. Network meta-analysis showed high-certainty evidence that for our primary outcome, 'time to treatment failure', for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: eventrate 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and eventrate was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs. For people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or eventrate in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), eventrate 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09). Network meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures. Network meta-analysis also showed high- to moderate-certainty evidence that, for 'time to first seizure,' in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, eventrate, zonisamide and lacosamide) for either seizure type. Generally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results. The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.
AUTHORS' CONCLUSIONS
High-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug eventrate, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and eventrate would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) is needed.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Humans; Network Meta-Analysis; Phenytoin
PubMed: 35363878
DOI: 10.1002/14651858.CD011412.pub4 -
The Cochrane Database of Systematic... Jun 2016Acupuncture is often used for migraine prevention but its effectiveness is still controversial. We present an update of our Cochrane review from 2009. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acupuncture is often used for migraine prevention but its effectiveness is still controversial. We present an update of our Cochrane review from 2009.
OBJECTIVES
To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than sham (placebo) acupuncture; and c) as effective as prophylactic treatment with drugs in reducing headache frequency in adults with episodic migraine.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL: 2016, issue 1); MEDLINE (via Ovid, 2008 to January 2016); Ovid EMBASE (2008 to January 2016); and Ovid AMED (1985 to January 2016). We checked PubMed for recent publications to April 2016. We searched the World Health Organization (WHO) Clinical Trials Registry Platform to February 2016 for ongoing and unpublished trials.
SELECTION CRITERIA
We included randomized trials at least eight weeks in duration that compared an acupuncture intervention with a no-acupuncture control (no prophylactic treatment or routine care only), a sham-acupuncture intervention, or prophylactic drug in participants with episodic migraine.
DATA COLLECTION AND ANALYSIS
Two reviewers checked eligibility; extracted information on participants, interventions, methods and results, and assessed risk of bias and quality of the acupuncture intervention. The primary outcome was migraine frequency (preferably migraine days, attacks or headache days if migraine days not measured/reported) after treatment and at follow-up. The secondary outcome was response (at least 50% frequency reduction). Safety outcomes were number of participants dropping out due to adverse effects and number of participants reporting at least one adverse effect. We calculated pooled effect size estimates using a fixed-effect model. We assessed the evidence using GRADE and created 'Summary of findings' tables.
MAIN RESULTS
Twenty-two trials including 4985 participants in total (median 71, range 30 to 1715) met our updated selection criteria. We excluded five previously included trials from this update because they included people who had had migraine for less than 12 months, and included five new trials. Five trials had a no-acupuncture control group (either treatment of attacks only or non-regulated routine care), 15 a sham-acupuncture control group, and five a comparator group receiving prophylactic drug treatment. In comparisons with no-acupuncture control groups and groups receiving prophylactic drug treatment, there was risk of performance and detection bias as blinding was not possible. Overall the quality of the evidence was moderate. Comparison with no acupunctureAcupuncture was associated with a moderate reduction of headache frequency over no acupuncture after treatment (four trials, 2199 participants; standardised mean difference (SMD) -0.56; 95% CI -0.65 to -0.48); findings were statistically heterogeneous (I² = 57%; moderate quality evidence). After treatment headache frequency at least halved in 41% of participants receiving acupuncture and 17% receiving no acupuncture (pooled risk ratio (RR) 2.40; 95% CI 2.08 to 2.76; 4 studies, 2519 participants) with a corresponding number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 6); there was no indication of statistical heterogeneity (I² = 7%; moderate quality evidence). The only trial with post-treatment follow-up found a small but significant benefit 12 months after randomisation (RR 2.16; 95% CI 1.35 to 3.45; NNT 7; 95% 4 to 25; 377 participants, low quality evidence). Comparison with sham acupunctureBoth after treatment (12 trials, 1646 participants) and at follow-up (10 trials, 1534 participants), acupuncture was associated with a small but statistically significant frequency reduction over sham (moderate quality evidence). The SMD was -0.18 (95% CI -0.28 to -0.08; I² = 47%) after treatment and -0.19 (95% CI -0.30 to -0.09; I² = 59%) at follow-up. After treatment headache frequency at least halved in 50% of participants receiving true acupuncture and 41% receiving sham acupuncture (pooled RR 1.23, 95% CI 1.11 to 1.36; I² = 48%; 14 trials, 1825 participants) and at follow-up in 53% and 42%, respectively (pooled RR 1.25, 95% CI 1.13 to 1.39; I² = 61%; 11 trials, 1683 participants; moderate quality evidence). The corresponding NNTBs are 11 (95% CI 7.00 to 20.00) and 10 (95% CI 6.00 to 18.00), respectively. The number of participants dropping out due to adverse effects (odds ratio (OR) 2.84; 95% CI 0.43 to 18.71; 7 trials, 931 participants; low quality evidence) and the number of participants reporting adverse effects (OR 1.15; 95% CI 0.85 to 1.56; 4 trials, 1414 participants; moderate quality evidence) did not differ significantly between acupuncture and sham groups. Comparison with prophylactic drug treatmentAcupuncture reduced migraine frequency significantly more than drug prophylaxis after treatment ( SMD -0.25; 95% CI -0.39 to -0.10; 3 trials, 739 participants), but the significance was not maintained at follow-up (SMD -0.13; 95% CI -0.28 to 0.01; 3 trials, 744 participants; moderate quality evidence). After three months headache frequency at least halved in 57% of participants receiving acupuncture and 46% receiving prophylactic drugs (pooled RR 1.24; 95% CI 1.08 to 1.44) and after six months in 59% and 54%, respectively (pooled RR 1.11; 95% CI 0.97 to 1.26; moderate quality evidence). Findings were consistent among trials with I² being 0% in all analyses. Trial participants receiving acupuncture were less likely to drop out due to adverse effects (OR 0.27; 95% CI 0.08 to 0.86; 4 trials, 451 participants) and to report adverse effects (OR 0.25; 95% CI 0.10 to 0.62; 5 trials 931 participants) than participants receiving prophylactic drugs (moderate quality evidence).
AUTHORS' CONCLUSIONS
The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking.
Topics: Acupuncture Therapy; Female; Humans; Male; Migraine Disorders; Migraine with Aura; Migraine without Aura; Randomized Controlled Trials as Topic
PubMed: 27351677
DOI: 10.1002/14651858.CD001218.pub3 -
Brain Stimulation 2022Transcranial ultrasound stimulation (TUS) is gaining traction as a safe and non-invasive technique in human studies. There has been a rapid increase in TUS human studies... (Review)
Review
BACKGROUND
Transcranial ultrasound stimulation (TUS) is gaining traction as a safe and non-invasive technique in human studies. There has been a rapid increase in TUS human studies in recent years, with more than half of studies to date published after 2020. This rapid growth in the relevant body of literature necessitates comprehensive reviews to update clinicians and researchers.
OBJECTIVE
The aim of this work is to review human studies with an emphasis on TUS devices, sonication parameters, outcome measures, results, and adverse effects, as well as highlight future directions of investigation.
METHODS
A systematic review was conducted by searching the Web of Science and PubMed databases on January 12, 2022. Human studies of TUS were included.
RESULTS
A total of 35 studies were identified using focused/unfocused ultrasound devices. A total of 677 subjects belonging to diverse cohorts (i.e., healthy, chronic pain, dementia, epilepsy, traumatic brain injury, depression) were enrolled. The stimulation effects vary in a sonication parameter-dependant fashion. Clinical, neurophysiological, radiological and histological outcome measures were assessed. No severe adverse effects were reported in any of the studies surveyed. Mild symptoms were observed in 3.4% (14/425) of the subjects, including headache, mood deterioration, scalp heating, cognitive problems, neck pain, muscle twitches, anxiety, sleepiness and pruritis.
CONCLUSIONS
Although increasingly being used, TUS is still in its early phases. TUS can change short-term brain excitability and connectivity, induce long-term plasticity, and modulate behavior. New techniques should be used to further elucidate its underlying mechanisms and identify its application in novel populations.
Topics: Affect; Brain; Chronic Pain; Epilepsy; Humans; Ultrasonography
PubMed: 35533835
DOI: 10.1016/j.brs.2022.05.002 -
Frontiers in Public Health 2023The provisions of the United Nation's Sustainable Development Goals (SDGs) for disability-inclusive education have stimulated a growing interest in ascertaining the...
AIM
The provisions of the United Nation's Sustainable Development Goals (SDGs) for disability-inclusive education have stimulated a growing interest in ascertaining the prevalence of children with developmental disabilities globally. We aimed to systematically summarize the prevalence estimates of developmental disabilities in children and adolescents reported in systematic reviews and meta-analyses.
METHODS
For this umbrella review we searched PubMed, Scopus, Embase, PsycINFO, and Cochrane Library for systematic reviews published in English between September 2015 and August 2022. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. We reported the proportion of the global prevalence estimates attributed to country income levels for specific developmental disabilities. Prevalence estimates for the selected disabilities were compared with those reported in the Global Burden of Disease (GBD) Study 2019.
RESULTS
Based on our inclusion criteria, 10 systematic reviews reporting prevalence estimates for attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, developmental intellectual disability, epilepsy, hearing loss, vision loss and developmental dyslexia were selected from 3,456 identified articles. Global prevalence estimates were derived from cohorts in high-income countries in all cases except epilepsy and were calculated from nine to 56 countries. Sensory impairments were the most prevalent disabilities (approximately 13%) and cerebral palsy was the least prevalent disability (approximately 0.2-0.3%) based on the eligible reviews. Pooled estimates for geographical regions were available for vision loss and developmental dyslexia. All studies had a moderate to high risk of bias. GBD prevalence estimates were lower for all disabilities except cerebral palsy and intellectual disability.
CONCLUSION
Available estimates from systematic reviews and meta-analyses do not provide representative evidence on the global and regional prevalence of developmental disabilities among children and adolescents due to limited geographical coverage and substantial heterogeneity in methodology across studies. Population-based data for all regions using other approaches such as reported in the GBD Study are warranted to inform global health policy and intervention.
Topics: Adolescent; Child; Humans; Autism Spectrum Disorder; Cerebral Palsy; Developmental Disabilities; Dyslexia; Epilepsy; Intellectual Disability; Prevalence; Systematic Reviews as Topic
PubMed: 36891340
DOI: 10.3389/fpubh.2023.1122009 -
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 -
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 -
CNS Drugs Mar 2021Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A...
BACKGROUND
Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex.
OBJECTIVES
This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox-Gastaut syndrome.
METHODS
The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes.
RESULTS
Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.
CONCLUSIONS
The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.
Topics: Anticonvulsants; Cannabidiol; Case-Control Studies; Cross-Sectional Studies; Double-Blind Method; Epilepsies, Myoclonic; Epilepsy; Epileptic Syndromes; Humans; Lennox Gastaut Syndrome; Seizures
PubMed: 33754312
DOI: 10.1007/s40263-021-00807-y -
BMC Medicine May 2017Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis.
METHODS
MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes).
RESULTS
After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not.
CONCLUSION
The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42014008925.
Topics: Abnormalities, Drug-Induced; Adult; Anticonvulsants; Bayes Theorem; Child; Epilepsy; Female; Humans; Infant; Network Meta-Analysis; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Young Adult
PubMed: 28472982
DOI: 10.1186/s12916-017-0845-1