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European Journal of Medical Research Mar 2024Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of... (Review)
Review
BACKGROUND
Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients.
METHODS
The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here.
RESULTS
The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures.
CONCLUSIONS
Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.
Topics: Adult; Humans; Leukodystrophy, Metachromatic; Quality of Life; Cost of Illness
PubMed: 38494502
DOI: 10.1186/s40001-024-01771-1 -
Seizure Apr 2024Adequate pre-pregnancy counselling and education planning are essential to improve outcomes for offspring of women with epilepsy (OWWE). The current systematic review... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Adequate pre-pregnancy counselling and education planning are essential to improve outcomes for offspring of women with epilepsy (OWWE). The current systematic review and meta-analysis aimed to compare outcomes for OWWE and offspring of women without epilepsy (OWWoE).
METHODS
We conducted a systematic review and meta-analysis. We searched MEDLINE, EMBASE, CINAHL, PsycINFO (database inception-1 January 2023), OpenGrey, GoogleScholar, and hand-searched journals and reference lists of included studies to identify eligible studies. We placed no language restrictions and included observational studies concerning OWWE and OWWoE. We followed the PRIMSA checklist for abstracting data. The Newcastle-Ottawa Scale for risk of bias assessment was conducted independently by two authors with mediation by a third. We report pooled unadjusted odds ratios (OR) or mean differences (MD) with 95% confidence intervals (95CI) from random (I>50%) or fixed (I<50%) effects meta-analyses. Outcomes of interest included offspring autism, attention deficit/hyperactive disorder, intellectual disability, epilepsy, developmental disorder, intelligence, educational, and adulthood socioeconomic outcomes.
RESULTS
Of 10,928 articles identified, we included 21 in meta-analyses. OWWE had increased odds of autism (2 articles, 4,502,098 offspring) OR [95CI] 1·67 [1·54, 1·82], attention-deficit/hyperactivity disorder (3 articles, 957,581 offspring) 1·59 [1·44, 1·76], intellectual disability (2 articles, 4,501,786 children) 2·37 [2·13, 2·65], having special educational needs (3 articles, 1,308,919 children) 2·60 [1·07, 6·34]. OWWE had worse mean scores for full-scale intelligence (5 articles, 989 children) -6·05 [-10·31, -1·79]. No studies were identified that investigated adulthood socioeconomic outcomes.
CONCLUSIONS
Increased odds of poor outcomes are higher with greater anti-seizure medication burden including neurodevelopmental and educational outcomes. In fact, these two outcomes seem to be worse in OWWE compared to OWWoE, even if there was no ASM exposure during pregnancy, but further work is needed to take into account potential confounding factors.
Topics: Humans; Epilepsy; Female; Pregnancy; Adult; Pregnancy Complications; Neurodevelopmental Disorders; Educational Status; Socioeconomic Factors; Developmental Disabilities
PubMed: 38484631
DOI: 10.1016/j.seizure.2024.02.014 -
Frontiers in Neurology 2024Epilepsy is a common neurological condition affecting primary school learners, often leading to misconceptions, stigma, and limited social inclusion. These...
Epilepsy is a common neurological condition affecting primary school learners, often leading to misconceptions, stigma, and limited social inclusion. These misconceptions transpire because of a lack of knowledge regarding the condition and may lead to high school dropouts. This systematic review aimed to evaluate the effectiveness of epilepsy education programs on epilepsy-related knowledge and understanding, values and attitudes, and skills among primary school learners. A thorough search of electronic databases was conducted to identify relevant studies published between January 2000 and September 2023. Studies that satisfied the eligibility criteria were chosen, and two reviewers conducted data extraction independently. A narrative synthesis approach was utilised to analyse the findings. The review included 10 studies that satisfied the inclusion requirements. The epilepsy education interventions varied in content, duration, and delivery method. Findings indicated that diverse delivery methods, such as classroom-based programs, hospital-based programs, and community-centred interventions, effectively enhanced epilepsy-related knowledge and understanding, values and attitudes, and skills among primary school learners. This systematic review provides evidence that epilepsy education programs can effectively enhance epilepsy-related knowledge, understanding, values, attitudes, and skills among primary school learners. These findings support developing and implementing comprehensive guidelines for teaching epilepsy in primary schools, suggesting various delivery methods and integrating cultural values to promote optimal learning outcomes and social inclusion for learners with epilepsy.
PubMed: 38476196
DOI: 10.3389/fneur.2024.1356920 -
BMC Public Health Mar 2024Epilepsy contributes to a significant disease burden in children and adolescents worldwide. The incidence of childhood epilepsy is threefold higher in low and middle... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy contributes to a significant disease burden in children and adolescents worldwide. The incidence of childhood epilepsy is threefold higher in low and middle income countries compared in high-income countries. Epilepsy is a serious neurological condition associated with stigma and discrimination, an impaired quality of life, and other mental health related problems.
OBJECTIVE
This study is aimed to synthesize existing evidence and estimate the pooled prevalence and incidence of epilepsy in children and adolescents in Africa.
METHODS
A comprehensive and systematic search of relevant databases was conducted. The quality of each study was assessed using the Newcastle-Ottawa Quality Assessment Scale adapted for meta-analysis. Two reviewers screened retrieved articles, conducted critical appraisals, and extracted the data. Heterogeneity between studies was assessed by visual inspection of forest plots and statistically using Cochran's Q statistics and the I test. Publication bias was checked by visual inspection of funnel plots as well as statistically using Egger's correlation and Begg's regression tests. Finally, the pooled prevalence and incidence of childhood epilepsy were computed with 95% confidence intervals.
RESULT
In this review and meta-analysis 42 studies with 56 findings were included to compute the pooled prevalence of childhood epilepsy. On the other hand, 6 studies were included to estimate the combined incidence. The pooled prevalence of cumulative epilepsy was 17.3 per 1000 children. Whereas the pooled prevalence of active and lifetime epilepsy was 6.8 and 18.6 per 1000 children respectively. The pooled incidence of childhood epilepsy was 2.5 per 1000 children.
CONCLUSION
Nearly 1 in 50 children are suffering from epilepsy in Africa. However, little attention has been paid to the prevention and treatment of childhood epilepsy. Mass epilepsy screening, scaling up treatment coverage, and designing strict treatment follow up and monitoring mechanisms are recommended.
Topics: Child; Humans; Adolescent; Prevalence; Incidence; Quality of Life; Africa; Epilepsy
PubMed: 38475724
DOI: 10.1186/s12889-024-18236-z -
BMC Medicine Mar 2024Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy.
METHODS
The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case-control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights.
RESULTS
We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96-1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13-1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83-1.56).
CONCLUSIONS
While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy.
SYSTEMATIC REVIEW REGISTRATION
CRD42022342510.
Topics: Humans; Cross-Sectional Studies; Epilepsy; Smokers; Risk Factors; Smoking
PubMed: 38433201
DOI: 10.1186/s12916-024-03307-0 -
Epilepsia Open Apr 2024Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first-line add-on therapies in DS.
METHODS
We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trial (RCT) data for licensed add-on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% (clinically meaningful), ≥75% (profound), and 100% (seizure-free); serious adverse events (SAEs); discontinuations due to AEs.
RESULTS
We identified relevant data from two placebo-controlled RCTs for each drug. Stiripentol 50 mg/kg/day and fenfluramine 0.7 mg/kg/day had similar efficacy in achieving ≥50% (clinically meaningful) and ≥75% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: -20% to 22%; p = 0.93] and 6% [-15% to 27%; p = 0.59], respectively), and both were statistically superior (p < 0.05) to licensed dose regimens of cannabidiol (10 or 20 mg/kg/day, with/irrespective of clobazam) for these outcomes. Stiripentol was statistically superior in achieving seizure-free intervals compared to fenfluramine (RD = 26% [CI: 8% to 44%; p < 0.01]) and licensed dose regimens of cannabidiol. There were no significant differences in the proportions of patients experiencing SAEs. The risk of discontinuations due to AEs was lower for stiripentol, although the stiripentol trials were shorter.
SIGNIFICANCE
This NMA of RCT data indicates stiripentol, as a first-line add-on therapy in DS, is at least as effective as fenfluramine and both are more effective than cannabidiol in reducing convulsive seizures. No significant difference in the incidence of SAEs between the three add-on agents was observed, but stiripentol may have a lower risk of discontinuations due to AEs. These results may inform clinical decision-making and the continued development of guidelines for the treatment of people with DS.
PLAIN LANGUAGE SUMMARY
This study compared three drugs (stiripentol, fenfluramine, and cannabidiol) used alongside other medications for managing seizures in a severe type of epilepsy called DS. The study found that stiripentol and fenfluramine were similarly effective in reducing seizures and both were more effective than cannabidiol. Stiripentol was the best drug for stopping seizures completely based on the available clinical trial data. All three drugs had similar rates of serious side effects, but stiripentol had a lower chance of being stopped due to side effects. This information can help guide treatment choices for people with DS.
Topics: Humans; Cannabidiol; Anticonvulsants; Fenfluramine; Network Meta-Analysis; Seizures; Epilepsies, Myoclonic; Randomized Controlled Trials as Topic; Dioxolanes
PubMed: 38427284
DOI: 10.1002/epi4.12923 -
Frontiers in Neurology 2024Antiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide...
OBJECTIVE
Antiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.
METHODS
We searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger's regression was performed to detect publication bias analysis.
RESULTS
We included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group ( = 0.02, df = 4, -value = 0.9852) but a significant bias in the LCM group ( = 5.94, df = 3, -value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.
CONCLUSION
The use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.
PubMed: 38419702
DOI: 10.3389/fneur.2024.1295368 -
Singapore Medical Journal Feb 2024Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological...
BACKGROUND
Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis.
METHODS
A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies.
RESULTS
Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46).
CONCLUSION
In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.
PubMed: 38409761
DOI: 10.4103/singaporemedj.SMJ-2022-114 -
Frontiers in Neurology 2024Previous studies showed that vagus nerve stimulation (VNS) can improve cognitive function in patients with epilepsy, but there is still great controversy about the...
BACKGROUND
Previous studies showed that vagus nerve stimulation (VNS) can improve cognitive function in patients with epilepsy, but there is still great controversy about the effect of VNS on cognitive function in patients with epilepsy.
OBJECTIVE
To investigate the effect of VNS on the cognitive function of epilepsy patients.
METHODS
Clinical trials published in PubMed, The Cochrane Library, and Embase before September 20, 2022, were comprehensively searched. Primary outcomes were overall cognitive performance, executive function, attention, memory; Secondary outcomes were seizure frequency, mood, and quality of life (QOL). Random effects were used to calculate the pooled outcome.
RESULTS
Twenty clinical trials were included. There was no significant improvement in overall cognitive performance in patients with epilepsy after VNS treatment (SMD = 0.07; 95% CI: -0.12 to 0.26; I = 0.00%) compared to pre-treatment. Compared to pre-treatment, there was no significant difference in executive function (SMD = -0.50; 95% CI: -1.50 to 0.50; = 0.32), attention (SMD = -0.17; 95% CI: -0.43 to 0.09; = 0.21) and memory (SMD = 0.64; 95% CI: -0.11 to 1.39; = 0.09), but there were significant differences in seizure frequency, mood, and quality of life in patients with epilepsy after VNS.
CONCLUSION
This meta-analysis did not establish that VNS can significantly improve cognitive function in patients with epilepsy, but it shows that VNS can significantly improve the seizure frequency, mood and quality of life of patients with epilepsy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42023384059.
PubMed: 38405400
DOI: 10.3389/fneur.2024.1332882 -
Critical Care Explorations Feb 2024Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the... (Review)
Review
OBJECTIVES
Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients.
DATA SOURCES
MEDLINE, Cochrane Central Register of Controlled Trials, and Embase.
STUDY SELECTION
Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021.
DATA EXTRACTION
Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case-control studies, and risk-of-bias framework for clinical trials.
DATA SYNTHESIS
Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1-2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89-95%, pediatric: 80-97%), SE (adults: 54-100%, pediatric: 60-100%), and DS (adults: 60-90%, pediatric: 62-90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol.
CONCLUSIONS
Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed.
PubMed: 38384587
DOI: 10.1097/CCE.0000000000001050