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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 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
Maedica Dec 2023ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic...
ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic acidosis. A systematic review was conducted with the aim to evaluate the effect of STAN method compared with isolated CTG on perinatal and neonatal outcomes. A search of electronic databases (PubMed, Cochrane, Scopus) was conducted to identify randomized controlled trials (RCTs) in English language. Outcomes considered operative deliveries, fetal blood sampling (FBS), metabolic acidosis, perinatal and neonatal death, neonatal seizures, neonatal encephalopathy, transfer to the neonatal intensive care unit (NICU) and Apgar score. Seven RCTs were included in the present review. The first two RCTs showed that the combination of STAN and CTG was a better option than using CTG alone, because there was a documented reduction in the rate of operative deliveries due to fetal distress and metabolic acidosis. The following studies showed no statistically significant changes with the combination of methods, except from a reduction in FBS. The findings from the RCTs were inconclusive. Most studies did not demonstrate a superiority of the combination regarding operative deliveries and neonatal outcomes but there were many methodological differences between the trials.
PubMed: 38348066
DOI: 10.26574/maedica.2023.18.4.684 -
Frontiers in Human Neuroscience 2023The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no... (Review)
Review
BACKGROUND
The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no uniform treatment guidelines.
OBJECTIVE
To summarize the clinical characteristics of patients with anti-NMDAR encephalitis and to analyze the factors affecting the disease prognosis.
METHODS
A systematic analysis of medical records was conducted, and PubMed, Embase, and Cochrane Library were searched from January 1, 2011, to December 31, 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
This study included 472 case reports. Most patients had prodromal symptoms of about 2 weeks, including psychiatric symptoms (53.2%), flu-like symptoms (51.5%), and seizures (23.9%), among others. Poor prognoses were associated with patients who had autonomic instability ( = 0.010), central hypoventilation ( = 0.014), and ICU support ( = 0.002). Patients with a higher age of onset were more likely to develop central hypoventilation (OR 1.024, CI 1.006-1.042, = 0.009), cognitive impairment (OR 1.023, CI 1.009-1.037, = 0.001), and memory impairment (OR 1.034, CI 1.017-1.050, < 0.001), whereas patients with a lower age were more likely to have seizures (OR 0.979, CI 0.965-0.993, = 0.003). In this study, 97.0% of patients received immunotherapy, with the most commonly used treatment regimen being intravenous methylprednisolone (IVGC) and intravenous immunoglobulin (IVIG). When compared with other treatment regimens, the IVGC+IVIG regimen ( < 0.001) resulted in better prognoses.
CONCLUSION
When encountering patients with fever, headache, and initial psychiatric symptoms of unknown etiology, clinicians should test their CSF for antibodies to distinguish autoimmune encephalitis. Patients with autonomic instability, central hypoventilation, and ICU support had poorer prognoses. Clinicians should be aware that older patients are more likely to develop central hypoventilation, cognitive impairment, and memory impairment, while younger patients are more likely to develop seizures. The IVGC+IVIG treatment regimen has better prognoses than others. This study includes case reports, which have obvious selection bias, and there are no unified standards to measure the severity of the disease. Therefore, in the future, larger samples and randomized controlled trials are needed to evaluate the efficacy of different treatment regimens.
PubMed: 38053649
DOI: 10.3389/fnhum.2023.1261638 -
Neurological Sciences : Official... Sep 2023Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common... (Review)
Review
BACKGROUND AND AIMS
Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%). To date, 44 patients with FDXR mutations have been reported. We describe here on two new patients, siblings, who presented with a quite different phenotype compared to previously described patients.
METHODS
Clinical, neurophysiological, and genetic features of two siblings and a systematic literature review focused on the clinical spectrum of the disease are described.
RESULTS
Both patients presented with an acute-sub-acute onset of peripheral neuropathy and only in later stages of the disease developed the typical features of FDXR-associated disease.
INTERPRETATION
The peculiar clinical presentation at onset and the evolution of the disease in our patients and in some cases revised from the literature shed lights on a new possible phenotype of FDXR-associated disease: a peripheral neuropathy which can mimic an acute inflammatory disease.
Topics: Humans; Ataxia; Cerebellar Ataxia; Diagnosis, Differential; Mutation; Peripheral Nervous System Diseases; Phenotype; Ferredoxin-NADP Reductase
PubMed: 37046037
DOI: 10.1007/s10072-023-06790-0 -
The Journal of International Medical... Nov 2023Due to variability in reports, the aim of this meta-analysis was to evaluate the incidence and risk factors of post-stroke early seizures (ES) and post-stroke epilepsy... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Due to variability in reports, the aim of this meta-analysis was to evaluate the incidence and risk factors of post-stroke early seizures (ES) and post-stroke epilepsy (PSE).
METHODS
The MEDLINE, EMBASE and Web of Science databases were searched for post-stroke ES/PSE articles published on any date up to November 2020. Post-stroke ES included seizures occurring within 7 days of stroke, and PSE included at least one unprovoked seizure. Using random effects models, the incidence and risk factors of post-stroke ES and PSE were evaluated. The study was retrospectively registered with INPLASY (INPLASY2023100008).
RESULTS
Of 128 included studies in total, the incidence of post-stroke ES was 0.07 (95% confidence interval [CI] 0.05, 0.10) and PSE was 0.10 (95% CI 0.08, 0.13). The rates were higher in children than adults. Risk factors for post-stroke ES included hemorrhagic stroke (odds ratio [OR] 2.14, 95% CI 1.44, 3.18), severe strokes (OR 2.68, 95% CI 1.73, 4.14), cortical involvement (OR 3.09, 95% CI 2.11, 4.51) and hemorrhagic transformation (OR 2.70, 95% CI 1.58, 4.60). Risk factors for PSE included severe strokes (OR 4.92, 95% CI 3.43, 7.06), cortical involvement (OR 3.20, 95% CI 2.13, 4.81), anterior circulation infarcts (OR 3.28, 95% CI 1.34, 8.03), hemorrhagic transformation (OR 2.81, 95% CI 1.25, 6.30) and post-stroke ES (OR 7.24, 95% CI 3.73, 14.06).
CONCLUSION
Understanding the risk factors of post-stroke ES/PSE may identify high-risk individuals who might benefit from prophylactic treatment.
Topics: Adult; Child; Humans; Incidence; Seizures; Stroke; Epilepsy; Risk Factors
PubMed: 38008901
DOI: 10.1177/03000605231213231 -
Clinical Neurophysiology : Official... Jul 2024Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset....
OBJECTIVE
Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset. Specifically, SOPs with low-voltage fast activity (LVFA) are associated with seizure-free outcome (Engel I). However, several classifications and various terms corresponding to the same pattern have been reported, challenging its use in clinical practice.
METHOD
Following the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guideline, we performed a systematic review of studies describing SOPs along with accompanying figures depicting the reported SOP in SEEG.
RESULTS
Of 1799 studies, 22 met the selection criteria. Among the various SOPs, we observed that the terminology for low frequency periodic spikes exhibited the most variability, whereas LVFA is the most frequently used term of this pattern. Some SOP terms were inconsistent with standard EEG terminology. Finally, there was a significant but weak association between presence of LVFA and seizure-free outcome.
CONCLUSION
Divergent terms were used to describe the same SOPs and some of these terms showed inconsistencies with the standard EEG terminology. Additionally, our results confirmed the link between patterns with LVFA and seizure-free outcomes. However, this association was not strong.
SIGNIFICANCE
These results underline the need for standardization of SEEG terminology.
Topics: Humans; Electroencephalography; Seizures; Stereotaxic Techniques
PubMed: 38733701
DOI: 10.1016/j.clinph.2024.04.016 -
Diagnostics (Basel, Switzerland) Nov 2023Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any... (Review)
Review
BACKGROUND
Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection.
METHODS
This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023.
RESULTS
Among nine studies, a total of 3249 patients were evaluated, of which 984 patients received antiepileptic drugs (AEDs). No significant difference was observed in the frequency of seizure events between patients who were treated with antiepileptic drugs (AEDs) and those who were not. (RR 1.22, 95% CI 0.66 to 2.40; I = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (<7 days), and 9% (95% CI: 1% to 17%) in the late time period (>7 days), with significant heterogeneity between the studies (I = 91% and 97%, respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses.
CONCLUSIONS
The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.
PubMed: 37998550
DOI: 10.3390/diagnostics13223415 -
Frontiers in Neurology 2023Epilepsy is one of the most common neurological diseases, affecting people of any age. Although the treatments of epilepsy are more and more diverse, the uncertainty...
BACKGROUND
Epilepsy is one of the most common neurological diseases, affecting people of any age. Although the treatments of epilepsy are more and more diverse, the uncertainty regarding efficacy and adverse events still exists, especially in the control of childhood epilepsy.
METHODS
We performed a systematic review and meta- analysis following the Cochrane Handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Four databases including PubMed, Embase, Web of Science and Cochrane library were searched. Studies reporting the use of brivaracetam monotherapy or adjuvant therapy in children (aged ≤18 years) were eligible for inclusion. Each stage of the review was conducted by two authors independently. Random-effects models were used to combine effect sizes for the estimation of efficacy and safety.
RESULTS
A total of 1884 articles were retrieved, and finally 9 articles were included, enrolling 503 children with epilepsy. The retention rate of BRV treatment was 78% (95% CI: 0.64-0.91), the responder rate (reduction of seizure frequency ≥ 50%) was 35% (95% CI: 0.24-0.47), the freedom seizure rate (no seizure) was 18% (95% CI: 0.10-0.25), and the incidence rate of any treatment-emergent adverse events (TEAE) was 39% (95% CI: 0.09-0.68). The most common TEAE was somnolence, which had an incidence rate of 9% (95% CI: 0.07-0.12). And the incidence rate of mental or behavioral disorders was 12% (95% CI: 0.06-0.17).
CONCLUSION
Our systematic review and meta-analysis showed that BRV seemed to be safe and effective in the treatment of childhood epilepsy.
PubMed: 37483441
DOI: 10.3389/fneur.2023.1170780