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Seizure May 2024To compare the efficacy, safety, and tolerability of cenobamate with other newer anti-seizure medications (ASMs) including brivaracetam, eslicarbazepine, lacosamide,... (Meta-Analysis)
Meta-Analysis Comparative Study Review
PURPOSE
To compare the efficacy, safety, and tolerability of cenobamate with other newer anti-seizure medications (ASMs) including brivaracetam, eslicarbazepine, lacosamide, perampanel, and zonisamide, approved for adjunctive treatment of drug-resistant focal-onset seizures (FOS) in adults with epilepsy.
METHODS
A systematic literature review (SLR) was conducted to obtain relevant efficacy, safety, and tolerability data for ASMs for the treatment of drug-resistant FOS. All studies were thoroughly assessed for potential sources of heterogeneity and analysed via Bayesian network meta-analyses (NMAs). Efficacy outcomes were ≥50 % responder rate and seizure freedom during the maintenance period, which were modelled simultaneously using a multinomial Bayesian NMA. Safety and tolerability outcomes were the proportion of patients who experienced at least one treatment-emergent adverse event (TEAE) and the proportion who experienced at least one TEAE leading to discontinuation.
RESULTS
The SLR identified 76 studies, of which 23 were included in the Bayesian NMAs. Cenobamate was associated with statistically significant higher rates for the ≥50 % responder rate and seizure freedom outcomes compared with all ASMs analysed. The point estimates indicated that cenobamate was associated with higher rates of experiencing at least one TEAE and at least one TEAE leading to discontinuation compared with brivaracetam, lacosamide, and zonisamide; however, no results were statistically significant.
CONCLUSION
Cenobamate was associated with increased efficacy compared with all ASMs analysed. There were no statistically significant differences in the safety and tolerability outcomes. The results presented corroborate the conclusions drawn from previous published NMAs, which also highlight the notable efficacy of cenobamate in comparison with other ASMs.
Topics: Humans; Anticonvulsants; Network Meta-Analysis; Seizures; Carbamates; Epilepsies, Partial; Chlorophenols; Tetrazoles
PubMed: 38643679
DOI: 10.1016/j.seizure.2024.04.004 -
European Journal of Medical Research Mar 2024Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that... (Review)
Review
BACKGROUND
Dravet Syndrome (DS) is a rare and severe form of childhood epilepsy that is often refractory to conventional antiepileptic drugs. Emerging evidence suggests that Cannabidiol (CBD) offer therapeutic benefits for DS. This review aims to evaluate the efficacy and safety of CBD in pediatric patients with DS based on data from ten clinical trials.
METHODS
A review was conducted to identify clinical trials assessing the efficacy and safety of CBD in pediatric patients diagnosed with DS. PubMed, MEDLINE, Scopus, Web of Science, and relevant grey literature were systematically searched for relevant articles up to October 2023, and clinical trials within the last 10 years were included. The search strategy incorporated controlled vocabulary terms and keywords related to "Cannabidiol," "Dravet Syndrome," and "pediatric patients."
RESULTS
The analysis revealed promising efficacy outcomes. Notably, CBD demonstrated substantial reductions in seizure frequency, with some patients achieving seizure freedom. The findings emphasised the consistency of CBD's efficacy across different patient subgroups. The safety profile of CBD was generally acceptable, with adverse events often being manageable.
CONCLUSION
This review consolidates evidence from multiple clinical trials, affirming the potential of CBD as a promising treatment option for pediatric patients with DS. While further research is needed to address existing knowledge gaps, CBD's efficacy and acceptable safety profile make it a valuable addition to the therapeutic tools for DS.
Topics: Child; Humans; Anticonvulsants; Cannabidiol; Epilepsies, Myoclonic; Lennox Gastaut Syndrome; Seizures
PubMed: 38500226
DOI: 10.1186/s40001-024-01788-6 -
Epilepsy Research Jan 2024Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS), also referred to as electrical status epilepticus during sleep (ESES)...
INTRODUCTION
Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS), also referred to as electrical status epilepticus during sleep (ESES) or epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS or EE-CSWS), is a spectrum of rare childhood epileptic encephalopathies that can lead to long-term cognitive impairment. Despite the importance of early diagnosis and intervention for D/EE-SWAS, there is a paucity of well-controlled clinical trial data to inform treatment, and no approved treatments are available. To assess correlations between diagnosis, treatment, and outcomes in D/EE-SWAS, we carried out a systematic review of the literature.
METHODS
In August 2020, we conducted comprehensive database searches using search terms including "electrical status epilepticus," "ESES," "CSWS," and "Landau-Kleffner syndrome." Two or more independent reviewers screened titles, abstracts, and full-text articles for those that met the following criteria: prospective studies (randomized controlled trials [RCTs] or open-label trials), retrospective studies (drug evaluations or observational studies/chart reviews), and case series with ≥ 10 participants. Both interventional and non-interventional studies were included (i.e., drug intervention was not an inclusion criterion). Articles published before 2012, review articles, animal studies, and studies of surgical or dietary interventions were excluded. Standardized data extraction templates were used to capture data on study design, patient characteristics, interventions, and outcomes from each of the selected publications. Study quality was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for retrospective, observational studies.
RESULTS
A total of 34 studies were included for full data extraction, most of which were uncontrolled and observational. Interpretation of study outcomes was limited by small study populations, variability in inclusion criteria, and inconsistency in methods of assessment and reporting of outcomes, which resulted in large heterogeneity in patients and their presenting symptoms. Despite these limitations, some patterns could be discerned. Several studies found that longer duration of ESES and younger age at onset were correlated with more severe language and cognitive deficits. In addition, several studies reported an association between improvement in cognitive outcomes and reduction in electroencephalogram (EEG) abnormalities and/or seizure frequency. In the 16 prospective or retrospective studies that evaluated drug treatments (e.g., antiseizure medications, corticosteroids, and high-dose diazepam), there was some improvement in EEG, seizure, and/or cognitive outcomes, although the specific outcomes and rates of improvement reported varied from study to study.
CONCLUSION
Long-term cognitive deficits remain common in D/EE-SWAS, and data gaps exist in the literature that preclude an evidence-based approach to managing this complex epilepsy indication. Early intervention with more effective medications is needed to optimize long-term outcomes. Sufficiently powered, randomized, double-blind, controlled trials with standardized methods and predefined primary and secondary outcomes are needed.
Topics: Child; Humans; Cognition Disorders; Electroencephalography; Epilepsy, Generalized; Landau-Kleffner Syndrome; Randomized Controlled Trials as Topic; Sleep; Status Epilepticus
PubMed: 38157757
DOI: 10.1016/j.eplepsyres.2023.107278 -
Epilepsia Open May 2024To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). (Review)
Review
OBJECTIVE
To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE).
METHODS
We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis.
RESULTS
Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD.
SIGNIFICANCE
The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment.
PLAIN LANGUAGE SUMMARY
This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.
PubMed: 38798030
DOI: 10.1002/epi4.12939 -
Biomolecules Feb 2024Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published.
METHODS
We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology.
RESULTS
A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date.
CONCLUSIONS
It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.
Topics: Child; Adult; Humans; Epilepsy; Mutation; Cerebellum; Phenotype; Brain Injuries; Vesicular Transport Proteins
PubMed: 38540691
DOI: 10.3390/biom14030270 -
Journal of Clinical Anesthesia Jun 2024To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVE
To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function.
DESIGN
Systematic review and meta-analysis of randomized controlled trials.
SETTING
We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023.
PATIENTS
Patients undergoing non-obstetric surgery.
INTERVENTIONS
Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid.
MEASUREMENT
We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function.
MAIN RESULTS
We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min.
CONCLUSIONS
The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.
Topics: Humans; Antifibrinolytic Agents; Creatinine; Hemorrhage; Kidney Diseases; Tranexamic Acid
PubMed: 38387241
DOI: 10.1016/j.jclinane.2024.111417 -
Frontiers in Pediatrics 2024Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however,...
BACKGROUND
Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however, no consensus exists on applying LEV monotherapy among children with epilepsy.
OBJECTIVE
The present work focused on comparing the efficacy and safety of LEV and OXC monotherapy in treating children with epilepsy.
METHODS
We conducted a comprehensive search across multiple databases including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, VIP, and China Biology Medicine disc, covering studies from inception to August 26, 2023. We included randomized controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of LEV and OXC monotherapy for treating epilepsy in children. We utilized Cochrane Risk of Bias Tool in RevMan 5.3 software for assessing included RCTs quality. In addition, included cohort studies quality was determined using Newcastle-Ottawa Scale (NOS). A random-effects model was utilized to summarize the results.
RESULTS
This meta-analysis included altogether 14 studies, including 893 children with epilepsy. LEV and OXC monotherapy was not statistical different among children with epilepsy in seizure-free rate (relative risk [RR] = 1.010, 95% confidence interval [CI] [0.822, 1.242], > 0.05) and seizure frequency decrease of ≥50% compared with baseline [RR = 0.938, 95% CI (0.676, 1.301), > 0.05]. Differences in total adverse reaction rate [RR = 1.113, 95% CI (0.710, 1.744), > 0.05] and failure rate because of serious adverse reaction [RR = 1.001, 95% CI (0.349, 2.871), > 0.05] were not statistical different between LEV and OXC treatments among children with epilepsy. However, the effects of OXC monotherapy on thyroid among children with epilepsy was statistically correlated than that of LEV (thyroid stimulating hormone: standardized mean difference [SMD] = -0.144, 95% CI [-0.613, 0.325], > 0.05; free thyroxine: SMD = 1.663, 95% CI [0.179, 3.147], < 0.05).
CONCLUSION
The efficacy of LEV and OXC monotherapy in treating children with epilepsy is similar. However, OXC having a more significant effect on the thyroid than that of LEV. Therefore, LEV may be safer for children with epilepsy who are predisposed to thyroid disease than OXC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42024514016).
PubMed: 38711491
DOI: 10.3389/fped.2024.1336744 -
Brain and Behavior Aug 2023The phenotype of the chromosomal aberration 47, XXY exhibits considerable heterogenicity. In addition, epilepsy is extremely uncommon in individuals with this...
OBJECTIVE
The phenotype of the chromosomal aberration 47, XXY exhibits considerable heterogenicity. In addition, epilepsy is extremely uncommon in individuals with this chromosomal disorder. As a result, the clinical characteristics of epilepsy in these patients remain poorly understood.
METHODS
Clinical data and the evolution of epilepsy in a boy diagnosed with chromosomal aberration 47, XXY were collected and analyzed. Furthermore, a systematic literature review was conducted to examine the relationship between chromosomal aberration 47, XXY and epilepsy in children.
RESULTS
We identified a novel phenotype associated with the chromosomal anomaly 47, XXY in a 2-year-2-month-old boy who presented with self-limited epilepsy with autonomic seizures at onset, followed by developmental and/or epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS), which was responsive to corticosteroid treatment. Including the present case, we analyzed 21 cases of children diagnosed with epilepsy due to the presence of the 47, XXY chromosomal anomaly. The most common types of epilepsy were focal combined generalized epilepsy (n = 9), epileptic spasms (n = 6), and generalized epilepsy (n = 4). There were six cases of infantile epileptic spasm syndrome (IESS) (n = 5) and developmental and epileptic encephalopathy (n = 1), one case of Lennox-Gastaut syndrome, and one case of D/EE-SWAS. Apart from corticosteroids in IESS, 15 antiseizure medications (ASMs) were prescribed to eight children in this cohort, with valproate (n = 5) being the most frequently used.
CONCLUSIONS
The epilepsy types and syndromes associated with the chromosomal anomaly 47, XXY demonstrated considerable heterogeneity. Among the observed phenotypes, IESS and focal epilepsy, which displayed partial responsiveness to multiple ASMs, were the most prevalent.
Topics: Humans; Epilepsy; Chromosome Aberrations; Spasms, Infantile; Epileptic Syndromes; Epilepsies, Partial
PubMed: 37479950
DOI: 10.1002/brb3.3178 -
Epilepsy & Behavior : E&B Mar 2024The term 'functional/dissociative seizures (FDS)' refers to a paroxysmal, transient clinical manifestation that may include motor, sensory, vegetative, psychological and... (Review)
Review
INTRODUCTION
The term 'functional/dissociative seizures (FDS)' refers to a paroxysmal, transient clinical manifestation that may include motor, sensory, vegetative, psychological and cognitive signs, similar to the manifestations observed in epileptic seizures. In recent years, there has been an increase of literature in the field of brain imaging research on functional neurological disorders and, more specifically, on FDS. However, most of the studies have been carried out on limited samples. We propose an update of this review work by performing a systematic review of studies performed since 2017 in the field of neuroimaging in patients with FDS.
METHODS
We conducted a systematic review of the literature using the PRISMA methodology and reproduced most of the methodological elements of the latest systematic literature review.
RESULTS
Our work over the last five years has identified 14 articles. It is still difficult to isolate a distinct structure or network specifically involved in the mechanism of FDS. However, certain structures are recurrently involved in imaging studies, notably the amygdala, the orbitofrontal cortex, and the anterior cingulate cortex.
CONCLUSION
The contribution of neuroimaging may allow a more precise explanation of the disorder for patients, avoiding the stigma frequently associated with this diagnosis. as with other 'conversion' phenomena which have traditionally been considered only as 'medically unexplained'. In the longer term and beyond a better understanding of the physiopathology of the disorder, the challenge of this neuroimaging work would be to identify specific imaging biomarkers for a diagnosis of FDS.
Topics: Humans; Psychogenic Nonepileptic Seizures; Conversion Disorder; Dissociative Disorders; Seizures; Epilepsy
PubMed: 38281393
DOI: 10.1016/j.yebeh.2024.109654 -
Scandinavian Journal of Trauma,... Mar 2024Tranexamic acid (TXA) demonstrates therapeutic efficacy in the management of traumatic brain injury (TBI). The objective of this systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tranexamic acid (TXA) demonstrates therapeutic efficacy in the management of traumatic brain injury (TBI). The objective of this systematic review and meta-analysis was to evaluate the safety and effectiveness of TXA in patients with TBI.
METHODS
The databases, namely PubMed, Embase, Web of Science, and Cochrane Library databases, were systematically searched to retrieve randomized controlled trials (RCTs) investigating the efficacy of TXA for TBI from January 2000 to November 2023.
RESULTS
The present meta-analysis incorporates ten RCTs. Compared to the placebo group, administration of TXA in patients with TBI resulted in a significant reduction in mortality (P = 0.05), hemorrhage growth (P = 0.03), and volume of hemorrhage growth (P = 0.003). However, no significant impact was observed on neurosurgery outcomes (P = 0.25), seizure occurrence (P = 0.78), or pulmonary embolism incidence (P = 0.52).
CONCLUSION
The administration of TXA is significantly associated with reduced mortality and hemorrhage growth in patients suffering from TBI, while the need of neurosurgery, seizures, and incidence of pulmonary embolism remains comparable to that observed with placebo.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Hemorrhage; Brain Injuries, Traumatic; Pulmonary Embolism
PubMed: 38454455
DOI: 10.1186/s13049-024-01188-z