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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 -
Epilepsy & Behavior : E&B Aug 2023Epileptic syndromes affecting children can sometimes be refractory to pharmacological treatments. Cannabinoids, especially cannabidiol, began to be studied to contribute... (Review)
Review
INTRODUCTION
Epileptic syndromes affecting children can sometimes be refractory to pharmacological treatments. Cannabinoids, especially cannabidiol, began to be studied to contribute to the treatment of these syndromes, configuring an expanding research area. The aim of this paper was to evaluate the scientific evidence available in the literature regarding the use of cannabinoids in the therapy of children with epilepsy.
METHOD
This is a systematic literature review, carried out according to the structure of the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA), in the SCIELO, Cochrane Library, and MEDLINE databases. Observational studies or clinical trials were included, conducted in humans, addressing the use of cannabinoids in pediatric patients with epilepsy, published in the last 10 years.
RESULTS AND DISCUSSION
In all, 626 studies were found and analyzed, of which 29 were considered eligible for the research; studies indicated good efficacy, safety, and tolerability of cannabidiol in several syndromes, with emphasis on Lennox-Gastaut and Dravet syndromes, in addition to practical issues were perceived regarding the applicability and expectations of patients and physicians.
CONCLUSION
The use of cannabidiol was considered effective and safe, yet the studies were mostly carried out in the same countries.
Topics: Humans; Child; Cannabinoids; Cannabidiol; Anticonvulsants; Epilepsy; Epilepsies, Myoclonic
PubMed: 37390729
DOI: 10.1016/j.yebeh.2023.109330 -
Seizure Jul 2023The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS),... (Review)
Review
INTRODUCTION
The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.
METHODS
We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).
RESULTS
Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.
CONCLUSIONS
AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.
Topics: Humans; Down Syndrome; Epilepsy; Epilepsies, Myoclonic; Levetiracetam; Seizures; Alzheimer Disease; Electroencephalography; Anticonvulsants; Epilepsy, Generalized
PubMed: 37267668
DOI: 10.1016/j.seizure.2023.05.017 -
Epilepsia Mar 2024KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a...
OBJECTIVE
KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.
METHODS
Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.
RESULTS
Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).
SIGNIFICANCE
This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Young Adult; Electroencephalography; Epilepsies, Myoclonic; Myoclonic Epilepsies, Progressive; Potassium Channels; Seizures; Unverricht-Lundborg Syndrome
PubMed: 38231304
DOI: 10.1111/epi.17880 -
Epilepsy & Behavior : E&B Sep 2023Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence and predictive risk factors for drug-resistant IGE.
METHODS
We systematically searched three databases (PubMed, Embase, and Cochrane Library) in November 2022 and included 12 eligible studies which reported long-term outcomes (mean = 14.05) after antiseizure medications (ASMs) from 2001 to 2020. We defined drug resistance as the persistence of any seizure despite ASMs treatment (whether as monotherapies or in combination) given the criteria of drug resistance varied in original studies. A random-effects model was used to evaluate the prevalence of refractory IGE. Studies reporting potential poor prognostic factors were included for subsequent subgroup meta-analysis.
RESULTS
The pooled prevalence of drug resistance in IGE cohorts was 27% (95% CI: 0.19-0.36). Subgroup analysis of the risk factors revealed that the psychiatric comorbidities (odds ratio (OR): 4.87, 95% confidence interval (CI): 2.97-7.98), combined three seizure types (absences, myoclonic jerks, and generalized tonic-clonic seizures) (OR: 5.37, 95% CI: 3.16-9.13), the presence of absence seizure (OR: 4.38, 95% CI: 2.64-7.28), generalized polyspike trains (GPT) (OR: 4.83, 95% CI: 2.42-9.64), sex/catamenial epilepsy (OR: 3.25, 95% CI: 1.97-5.37), and status epilepticus (OR: 5.94, 95% CI: 2.23-15.85) increased the risk of poor prognosis. Other factors, including age onset, family history, and side effects of ASMs, were insignificantly associated with a higher incidence of refractory IGE.
CONCLUSION
Drug resistance is a severe complication of IGE. Further standardized research about clinical and electroencephalography factors is warranted.
Topics: Humans; Anticonvulsants; Prevalence; Epilepsy, Generalized; Seizures; Drug Resistant Epilepsy; Risk Factors; Immunoglobulin E
PubMed: 37523796
DOI: 10.1016/j.yebeh.2023.109364 -
Seizure Jun 2024Sleep disturbances significantly impact the lives of individuals with Juvenile Myoclonic Epilepsy (JME). This study aimed to investigate sleep studies, disturbances, and... (Review)
Review
Sleep disturbances significantly impact the lives of individuals with Juvenile Myoclonic Epilepsy (JME). This study aimed to investigate sleep studies, disturbances, and the impact of anti-seizure drugs on sleep in JME patients. Relevant studies were retrieved from the National Library of Medicine (Pubmed) database and the Cochrane Library utilizing the search terms "Juvenile Myoclonic Epilepsy" and "sleep". A total of 160 papers' review, data extraction, and resolution of discrepancies were performed independently by two reviewers according to the PRISMA protocol and were registered in PROSPERO (CRD42023472439). A systematic review of 31 studies was conducted, encompassing various methodologies, including sleep questionnaires (Pittsburgh Sleep Quality Index (n = 13), Epworth Sleepiness Scale (n = 10)), polysomnography (n = 8), EEG (n = 9), actigraphy (n = 1), and transcranial magnetic stimulation (n = 1). Most studies were hospital-based (n = 31), cross-sectional (n = 11), and prospective (n = 25). Patients with JME exhibit a higher prevalence of sleep disturbances, worse quality of sleep (n = 4), daytime sleepiness (n = 2), sleep efficiency (n = 7), and increased sleep latency (n = 1) compared to controls. These disruptions are characterized by increased wakefulness (n = 3), frequent arousals (n = 3), decreased REM sleep (n = 2), and conflicting NREM sleep findings (n = 3). Additional sleep-related issues observed in JME patients include insomnia (n = 1) and increased prevalence of parasomnias such as nightmares and sleep talking. Periodic limb movement and obstructive sleep apnea are similar or less frequent (3/28). REM behavioral disorders and sleepwalking were not seen. Valproate showed conflicting effects on sleep (n = 7), while levetiracetam did not impact sleep (n = 1). These findings underlined the need for more sufficient evidence of sleep studies in JME. Future research should prioritize understanding the nature of sleep in JME and its impact on management.
PubMed: 38908143
DOI: 10.1016/j.seizure.2024.05.014 -
Epilepsy & Behavior : E&B Aug 2023Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of the article was to summarize knowledge and recent developments in the field of reading-induced seizures by reviewing all cases for which data were reported within the last three decades.
METHODS
A scoping systematic review of demographic, clinical, electroencephalography (EEG) and imaging data of cases with reading-induced seizures reported in PubMed and Web of Science between 1991-01-01 and 2022-08-21 and a meta-analysis of the findings.
RESULTS
The review included 101 case reports of epilepsy with reading-induced seizures (EwRIS) from 42 articles. The phenomenon was more prevalent among males (67, 66.3% vs. 34, 33.7%) with an average age of onset of 18.3 ± 7.9 years. When reported, 30.8% of patients had a family history of epilepsy. Orofacial reflex myocloni (ORM) were the most frequent manifestation (68, 67.3% cases), other presentations, mostly in addition to ORM, included visual, sensory or cognitive symptoms, non-orofacial myoclonic seizures, and absence seizures. Within the sample, 75 (74.3%) patients were identified as having primary reading epilepsy (PRE), 13 (12.9%) idiopathic generalised epilepsy (IGE) and 13 (12.9%) focal epilepsies. Advanced EEG and functional imaging data suggest that the basic mechanism of reading-induced seizures is probably similar despite different symptoms and consists of upregulation of the complex cerebral subsystem involved in reading. Ictogenesis and resulting symptomatology may then depend on predominant sensory or proprioceptive stimuli during reading.
CONCLUSION
In most cases, reading-induced seizures were confirmed to belong to a particular epilepsy syndrome of PRE. However, there were substantial subgroups with IGE and focal epilepsies. Most likely, reading-induced seizures occur as an abnormal response to extero- or proprioceptive input into an upregulated cortical network subserving reading. Most recent researchers consider EwRIS a system epilepsy.
Topics: Adolescent; Adult; Child; Humans; Male; Young Adult; Electroencephalography; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Epilepsy, Reflex; Immunoglobulin E; Myoclonus; Seizures
PubMed: 37437391
DOI: 10.1016/j.yebeh.2023.109346 -
Epilepsy & Behavior : E&B Mar 2024This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and adolescents with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC).
METHODS
A comprehensive literature search was performed using PubMed, Medline, Embase, and Cochrane library databases from inception to October 13, 2023. We included published studies for a systematic review and a network meta-analysis (NMA). The efficacy and safety were reported in terms of a 50% response rate and dropout rate along with serious adverse events (SAEs). The outcomes were ranked with the surface under the cumulative ranking curve (SUCRA).
RESULTS
Twenty eligible trials with 5516 patients and 21 interventions, including placebo, contributed to the analysis. Included ASMs were brivaracetam (BRV), cenobamate (CBM), cannabidiol (CBD), fenfluramine (FFM), everolimus (ELM), and soticlestat (SLT). The six new ASMs were compared in four different epilepsy subtypes. In focal epilepsy treatment, BRV seemed to be safe [vs placebo, risk ratio (RR) = 0.69, 95 % confidence interval (CI): 0.25-1.91] and effective (vs placebo, RR = 2.18, 95 % CI: 1.25-3.81). In treating focal epilepsy, CBM 300 mg was more effective at a 50 % response rate (SUCRA 91.8 %) compared with BRV and CBD. However, with the increase in dosage, more SAEs (SUCRA 85.6 %) appeared compared with other ASMs. CBD had good efficacy on LGS (SUCRA 88.4) and DS (SUCRA 66.2), but the effect on adult focal epilepsy was not better than that of placebo [vs placebo, RR = 0.83 (0.36-1.93)]. The NMA indicated that the likelihood of the most appropriate intervention (SUCRA 91.2 %) with minimum side effects(SUCRA 12.5 %)for the DS was FFM. Compared with CBD, high exposure to ELM demonstrated a more effective treatment of TSC (SUCRA 89.7 %). More high-quality SLT studies are needed to further evaluate the efficacy and safety. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed no significant funnel plot asymmetry.
CONCLUSIONS
This NMA indicated that the most effective treatment strategy for focal epilepsy, DS, Lennox-Gastaut syndrome, and TSC, respectively, included CBM 300 mg, FFM, CBD, and ELM. However, the aforementioned findings need further confirmation.
Topics: Adult; Adolescent; Humans; Lennox Gastaut Syndrome; Network Meta-Analysis; Cannabidiol; Epilepsy; Epilepsies, Myoclonic; Epilepsies, Partial; Everolimus; Anticonvulsants; Carbamates; Chlorophenols; Tetrazoles
PubMed: 38277848
DOI: 10.1016/j.yebeh.2024.109653 -
Seizure Aug 2023Dyke-Davidoff-Masson syndrome (DDMS), or cerebral hemiatrophy, was first described in 1933. It is characterised by cerebral injury that causes hypoplasia in one of the... (Review)
Review
INTRODUCTION
Dyke-Davidoff-Masson syndrome (DDMS), or cerebral hemiatrophy, was first described in 1933. It is characterised by cerebral injury that causes hypoplasia in one of the cerebral hemispheres. The disease has different clinical degrees and two aetiologies: congenital and acquired. Radiological findings depend on the degree of injury and the patient's age at the time.
OBJECTIVE
To provide information on the main clinical and radiological characteristics of this disease.
METHODS
A systematic review of the PubMed, MEDLINE, and LILACS databases was conducted using only one keyword. Dyke-Davidoff-Masson syndrome. A total of 223 studies were identified, and the results are presented in tables and graphics.
RESULTS
The mean age of the patients was 19.44 (0-83 years), and the majority were male (55.32%). The most common types of epileptic seizures were generalised tonic-clonic seizures (31 cases), focal impaired awareness seizures (20 cases), focal motor seizures (13 cases), focal to bilateral tonic-clonic seizures (nine cases), and focal myoclonic seizures (one case). The main features of the disease were rapid deep tendon reflexes and extensor cutaneous-plantar tendon reflexes (30 cases - 16%), contralateral hemiparesis or hemiplegia (132 cases - 70%), gait alterations (16 cases - 9%), facial paralysis (nine cases - 5%), facial asymmetry (58 cases - 31%), limb asymmetry (20 cases - 11%), delayed developmental milestones (39 cases - 21%), intellectual disability (87 cases - 46%), and language/speech disorders (29 cases - 15%). Left hemisphere atrophy was the most prevalent.
CONCLUSION
DDMS is a rare syndrome, and several questions regarding this disease remain unanswered. This systematic review aims to elucidate the most common clinical and radiological aspects of the disease and emphasises the need for further investigation.
Topics: Humans; Male; Female; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Magnetic Resonance Imaging; Seizures; Epilepsy; Hemiplegia; Atrophy
PubMed: 37327751
DOI: 10.1016/j.seizure.2023.04.020