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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 -
Neurology Jul 2023Functional neurologic disorder (FND) represents genuine involuntary neurologic symptoms and signs including seizures, weakness, and sensory disturbance, which have...
BACKGROUND AND OBJECTIVES
Functional neurologic disorder (FND) represents genuine involuntary neurologic symptoms and signs including seizures, weakness, and sensory disturbance, which have characteristic clinical features, and represent a problem of voluntary control and perception despite normal basic structure of the nervous system. The historical view of FND as a diagnosis of exclusion can lead to unnecessary health care resource utilization and high direct and indirect economic costs. A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess these economic costs and to assess for any cost-effective treatments.
METHODS
We searched electronic databases (PubMed, PsycInfo, MEDLINE, EMBASE, and the National Health Service Economic Evaluations Database of the University of York) for original, primary research publications between inception of the databases and April 8, 2022. A hand search of conference abstracts was also conducted. Key search terms included "functional neurologic disorder," "conversion disorder," and "functional seizures." Reviews, case reports, case series, and qualitative studies were excluded. We performed a descriptive and qualitative thematic analysis of the resulting studies.
RESULTS
The search resulted in a total of 3,244 studies. Sixteen studies were included after screening and exclusion of duplicates. These included the following: cost-of-illness (COI) studies that were conducted alongside cohort studies without intervention and those that included a comparator group, for example, another neurologic disorder (n = 4); COI studies that were conducted alongside cohort studies without intervention and those that did not include a comparator group (n = 4); economic evaluations of interventions that were either pre-post cohort studies (n = 6) or randomized controlled trials (n = 2). Of these, 5 studies assessed active interventions, and 3 studies assessed costs before and after a definitive diagnosis of FND. Studies showed an excess annual cost associated with FND (range $4,964-$86,722 2021 US dollars), which consisted of both direct and large indirect costs. Studies showed promise that interventions, including provision of a definitive diagnosis, could reduce this cost (range 9%-90.7%). No cost-effective treatments were identified. Study comparison was limited by study design and location heterogeneity.
DISCUSSION
FND is associated with a significant use of health care resources, resulting in economic costs to both the patient and the taxpayer and intangible losses. Interventions, including accurate diagnosis, seem to offer an avenue toward reducing these costs.
Topics: Nervous System Diseases; Humans; Conversion Disorder; Seizures; Health Care Costs; Cost-Benefit Analysis
PubMed: 37339887
DOI: 10.1212/WNL.0000000000207388 -
Epilepsy & Behavior : E&B Jan 2024Guidance documents play a pivotal role in shaping the management of status epilepticus (SE). However, the methodological quality of these documents remains uncertain. In... (Review)
Review
Guidance documents play a pivotal role in shaping the management of status epilepticus (SE). However, the methodological quality of these documents remains uncertain. In this systematic review, we comprehensively searched 12 literature and guideline databases to assess the quality of clinical practice guidelines and consensus statements related to SE management using the AGREE II methodology. Additionally, we summarized the associated recommendations. We identified a total of 14 clinical practice guidelines and 11 consensus statements spanning the period from 1993 to 2022. The median score for clarity of presentation was 71.8% (ranging from 15.3% to 91.7%), indicating generally good clarity. However, the aspect of editorial independence received poor ratings, with a median score of 32.1% (ranging from 0% to 83.3%). Notably, the 2016 guideline published by the American Epilepsy Society in Epilepsy (AES) received the highest overall scores. Across these guidance documents, there was consistency in the definition and diagnosis of SE. However, significant variability was observed in therapeutic recommendations, particularly in terms of the timing for adding or changing medications. The methodological approaches used in most SE guidance documents require improvement, and the disparities in recommendations highlight existing gaps in evidence. Enhanced methodological rigor results in increased standardization of the guideline, consequently augmenting its reference value. Given the urgency of SE as an emergency condition, it is imperative that these documents also address relevant management strategies before admission.
Topics: Humans; Consensus; Epilepsy; Hospitalization; Status Epilepticus; United States; Practice Guidelines as Topic
PubMed: 38128315
DOI: 10.1016/j.yebeh.2023.109555 -
Diagnostics (Basel, Switzerland) Jul 2023Treatment of Wilson's disease (WD), an inherited disease characterized by copper overload, is lifelong and there is the possibility that copper deficiency (CD) may... (Review)
Review
BACKGROUND
Treatment of Wilson's disease (WD), an inherited disease characterized by copper overload, is lifelong and there is the possibility that copper deficiency (CD) may occur. We systematically reviewed the literature to describe treatment patterns, symptoms and outcomes associated with CD.
METHODS
Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, the PubMed database was searched up to 6 April 2023.
RESULTS
Across 17 articles, 20 cases of CD were described, most commonly (15 cases) in WD patients treated with zinc salts (ZS), less often on combined chelator and ZS therapy (3 cases), molybdate salts plus ZS (1), or molybdate alone (1). CD symptoms occurred insidiously, including sideroblastic anemia, neutropenia, axonal sensory neuropathy, posterior cord myelopathy and increased ratio of epileptic seizures (or epilepsy). CD diagnosis was based on symptoms and severely reduced urinary copper excretion (<20 µg/24 h [<0.3 µmol/24 h] on ZS, or <100 µg/24 h [<1.6 µmol/24 h] on chelators) with low total serum copper and ceruloplasmin.
CONCLUSIONS
Awareness of CD and regular monitoring of copper metabolism is needed during WD treatment. Temporary cessation of anti-copper treatment usually reverses serum copper reductions as well as pancytopenia; however, some symptoms, especially neuropathy and myelopathy, may persist.
PubMed: 37510170
DOI: 10.3390/diagnostics13142424 -
Reviews on Environmental Health Dec 2023Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of... (Review)
Review
Since 2016, numerous American and Canadian diplomats and secret (intelligence) agents in Cuba, China, and other places in the world have experienced an abrupt onset of unusual clinical symptoms including, tinnitus, visual problems, vertigo, and cognitive difficulties, after they encountered strange sounds; this has been called "Havana syndrome" (HS). MEDLINE, Scopus, and Ovid databases from 2016 until 24 September 2021 were systematically searched for the related published manuscripts. The following search strategy was implemented: "Havana syndrome" OR "Neurological Symptoms and US Diplomats". The primary search yielded 120 publications. Only five original studies and 18 non-original articles were considered to be relevant. While these studies provided a constellation of signs and symptoms for HS, none provided a good level of evidence. In conclusion, Havana syndrome is a nonspecific neurological illness with an unidentified causative factor(s), an acute phase of auditory-vestibular symptoms and a chronic phase of nonspecific neurobehavioral symptoms. This syndrome should be considered and investigated as a health concern, and not as a political issue.
Topics: Canada; China; Cuba; United States; Nervous System Diseases
PubMed: 35962646
DOI: 10.1515/reveh-2021-0182 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
Frontiers in Nutrition 2023Central nervous system (CNS) disorders present a growing and costly global health challenge, accounting for over 11% of the diseases burden in high-income countries.... (Review)
Review
Central nervous system (CNS) disorders present a growing and costly global health challenge, accounting for over 11% of the diseases burden in high-income countries. Despite current treatments, patients often experience persistent symptoms that significantly affect their quality of life. Dietary polysaccharides have garnered attention for their potential as interventions for CNS disorders due to their diverse mechanisms of action, including antioxidant, anti-inflammatory, and neuroprotective effects. Through an analysis of research articles published between January 5, 2013 and August 30, 2023, encompassing the intervention effects of dietary polysaccharides on Alzheimer's disease, Parkinson's disease, depression, anxiety disorders, autism spectrum disorder, epilepsy, and stroke, we have conducted a comprehensive review with the aim of elucidating the role and mechanisms of dietary polysaccharides in various CNS diseases, spanning neurodegenerative, psychiatric, neurodevelopmental disorders, and neurological dysfunctions. At least four categories of mechanistic bases are included in the dietary polysaccharides' intervention against CNS disease, which involves oxidative stress reduction, neuronal production, metabolic regulation, and gut barrier integrity. Notably, the ability of dietary polysaccharides to resist oxidation and modulate gut microbiota not only helps to curb the development of these diseases at an early stage, but also holds promise for the development of novel therapeutic agents for CNS diseases. In conclusion, this comprehensive review strives to advance therapeutic strategies for CNS disorders by elucidating the potential of dietary polysaccharides and advocating interdisciplinary collaboration to propel further research in this realm.
PubMed: 38075226
DOI: 10.3389/fnut.2023.1299117 -
Frontiers in Neurology 2023This study aimed to evaluate the retina and microvascular alterations with optical coherence tomography (OCT) or optical coherence tomography angiography (OCTA) in...
OBJECTIVE
This study aimed to evaluate the retina and microvascular alterations with optical coherence tomography (OCT) or optical coherence tomography angiography (OCTA) in patients with migraine with aura (MA) and migraine without aura (MO).
METHODS
PubMed, Embase, and Cochrane Library databases were searched to find relevant literature on patients with MA or MO using OCT/OCTA devices. The eligible data were analyzed by Stata Software (version 15.0).
RESULTS
There were 16 studies identified, involving 379 eyes with MA, 583 eyes with MO, and 658 eyes of healthy controls. The thickness of the peripapillary retinal nerve fiber layer (pRNFL) of patients with MA decreased significantly in most regions. The foveal avascular zone (FAZ) area and perimeter in MA patients significantly enlarged, while the perfusion density (PD) in the macular deep capillary plexus (mDCP) significantly decreased in the whole image and its subregions except for the fovea, with the PD in radial peripapillary capillary (RPC) decreasing inside the disk. Patients with MO demonstrated a significantly decreased thickness of pRNFL in most regions, and the FAZ parameters were significantly enlarged. No statistical significance was observed in the retina and microvascular features of patients with MA and MO.
CONCLUSION
The eyes affected by MA and MO demonstrated significantly reduced thickness of pRNFL and enlarged FAZ. Patients with MA showed retinal microvascular impairments, including a decreased PD in mDCP. The OCT and OCTA could detect membrane morphology and circulation status in migraine and might provide the basis for the diagnosis and follow-up of patients with migraine.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, CRD42023397653.
PubMed: 37840933
DOI: 10.3389/fneur.2023.1241778 -
Cureus Oct 2023Gluten, as a term, causes unease among a vast majority of the population. The reason is the body's inability to process gluten, causing various pathological... (Review)
Review
Gluten, as a term, causes unease among a vast majority of the population. The reason is the body's inability to process gluten, causing various pathological manifestations. While celiac disease is predominantly a gastrointestinal disease, it also has various extra-intestinal manifestations. Many children receive diagnoses of idiopathic neuropsychiatric symptoms such as epilepsy, attention-deficit hyperactivity disorder (ADHD), restless leg syndrome (RLS), and peripheral neuropathy without ever finding the root cause. A majority of these cases may be associated with celiac disease if only their antibody titers and other appropriate investigations were conducted. The treatment of these manifestations may be eliminated or at least controllable with dietary modification to a gluten-free diet (GFD). In this paper, we will discuss the pathology of celiac disease and the impact of GFD on the neuropsychiatric aspects of this disease, which is of higher prevalence in the pediatric population. A comprehensive literature search was conducted in prominent databases, namely PubMed and Google Scholar, to include studies that provided individual-level data on the neuropathological manifestations and the impact of a GFD on extra-intestinal manifestations of celiac disease. The research protocol was registered in the PROSPERO database (International Prospective Register of Systematic Reviews) with the registration ID: CRD42023415100. Based on the inclusion and exclusion criteria, we included prospective studies, observational studies, and case reports on pediatric patients with biopsy-proven celiac disease, serologically positive celiac disease, celiac disease with neuropsychiatric manifestations, and studies reporting the impact of GFD. After a rigorous quality assessment to remove the risk of bias, we finally included 20 studies to be discussed. In 6 (30%) studies, patients with neuropsychiatric manifestations had positive serology findings and a relatively higher grade of biopsy results. Seven studies discussed the positive impact of GFD. Five of these seven studies reported statistically significant results (p ≤ 0.001). Our study suggests that gluten plays a role in the severity of neuropsychiatric manifestations of celiac disease. Considering the results of our study, we can see that GFD does impact the prognosis of the disease. Neuropsychiatric findings without gastrointestinal manifestations are more common in the pediatric age group. We have clear evidence that several neurological conditions (neuropathy, ADHD, epilepsy, and RLS) have not only a significant association with gluten but can also potentially benefit from GFD. Thus, screening, with a combination of serological, biopsy, and imaging techniques, must be adapted into the guidelines for early detection and induction of GFD. Furthermore, studies should aim at introducing GFD in the pediatric population as a mode of primary prevention. In conclusion, our review underscores the importance of gluten while dealing with idiopathic neurological conditions in children and hopes to shed light on this commonly misdiagnosed and easily manageable disease.
PubMed: 38022342
DOI: 10.7759/cureus.47062 -
Neuropsychology Review Jun 2024Mathematics incorporates a broad range of skills, which includes basic early numeracy skills, such as subitizing and basic counting to more advanced secondary skills... (Meta-Analysis)
Meta-Analysis Review
Mathematics incorporates a broad range of skills, which includes basic early numeracy skills, such as subitizing and basic counting to more advanced secondary skills including mathematics calculation and reasoning. The aim of this review was to undertake a detailed investigation of the severity and pattern of early numeracy and secondary mathematics skills in people with epilepsy. Searches were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Twenty adult studies and 67 child studies were included in this review. Overall, meta-analyses revealed significant moderate impairments across all mathematics outcomes in both adults (g= -0.676), and children (g= -0.593) with epilepsy. Deficits were also observed for specific mathematics outcomes. For adults, impairments were found for mathematics reasoning (g= -0.736). However, two studies found that mathematics calculation was not significantly impaired, and an insufficient number of studies examined early numeracy skills in adults. In children with epilepsy, significant impairments were observed for each mathematics outcome: early numeracy (g= -0.383), calculation (g= -0.762), and reasoning (g= -0.572). The gravity of impairments also differed according to the site of seizure focus for children and adults, suggesting that mathematics outcomes were differentially vulnerable to the location of seizure focus.
Topics: Humans; Epilepsy; Mathematics; Child; Adult
PubMed: 37490196
DOI: 10.1007/s11065-023-09600-8