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Epilepsy & Behavior : E&B Feb 2021Late-onset epilepsy (LOE) is closely associated with cerebrovascular disease, acting as both a marker of cerebrovascular disease (CVD) and occurring as a direct... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Late-onset epilepsy (LOE) is closely associated with cerebrovascular disease, acting as both a marker of cerebrovascular disease (CVD) and occurring as a direct consequence. Despite this, our understanding of LOE as a cerebrovascular phenomenon is in its infancy. LOE also appears to be a harbinger of dementia.
METHODS
A systematic review was performed to identify publications relating to LOE and identified observational studies, clinical studies, and radiological studies.
RESULTS
A meta-analysis of observational studies demonstrated that patients presenting with LOE experience an increased risk of subsequent stroke (weighted OR 3.88 (95% CI 2.76-5.46)). The additional studies demonstrated clinical and radiological evidence to support the premise that LOE is likely to reflect underlying cerebrovascular disease.
SIGNIFICANCE
Cerebrovascular disease risk factors convey increased risk of LOE and LOE can precede stroke and dementia, acting as an early marker for cerebrovascular risk. This may represent a potential point for intervention. There are a number of suggested mechanisms relating LOE to stroke; however, there is limited understanding of the natural history of LOE. Current data support the need for prospective research in order to understand the natural history of LOE and modify disease, in order to reduce the apparent sequelae of stroke and dementia.
Topics: Cerebrovascular Disorders; Epilepsy; Humans; Prospective Studies; Risk Factors; Stroke
PubMed: 33334717
DOI: 10.1016/j.yebeh.2020.107634 -
Neurological Sciences : Official... Apr 2023KCNT1 has been known to encode a subunit of the tetrameric sodium activated potassium channel (K1.1). Pathogenic variants of KCNT1, especially gain-of-function (GOF)... (Review)
Review
KCNT1 has been known to encode a subunit of the tetrameric sodium activated potassium channel (K1.1). Pathogenic variants of KCNT1, especially gain-of-function (GOF) variants, are associated with multiple epileptic disorders which are often refractory to conventional anti-seizure medications and summarized as KCNT1-related epilepsy. Although the detailed pathogenic mechanisms of KCNT1-related epilepsy remain unknown, increasing studies attempt to find effective medications for those patients by utilizing quinidine to inhibit hyperexcitable K1.1. However, it has been shown that controversial outcomes among studies and partial success in some individuals may be due to multiple factors, such as poor blood-brain barrier (BBB) penetration, mutation-dependent manner, phenotype-genotype associations, and rational therapeutic schedule. In recent years, with higher resolution of K1.1 structure in different activation states and advanced synthetic techniques, it improves the process performance of therapy targeting at K1.1 channel to achieve more effective outcomes. Here, we systematically reviewed the study history of quinidine on KCNT1-related epilepsy and its corresponding therapeutic effects. Then, we analyzed and summarized the possible causes behind the different outcomes of the application of quinidine. Finally, we outlooked the recent advances in precision medicine treatment for KCNT1-related epilepsy.
Topics: Humans; Quinidine; Anticonvulsants; Potassium Channels, Sodium-Activated; Epilepsy; Potassium Channels; Mutation; Nerve Tissue Proteins
PubMed: 36437393
DOI: 10.1007/s10072-022-06521-x -
Sleep Medicine Reviews Jun 2021This systematic review and meta-analysis aims to assess and quantify putative differences in sleep architecture, sleep efficiency, sleep timing and broadly-defined sleep... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aims to assess and quantify putative differences in sleep architecture, sleep efficiency, sleep timing and broadly-defined sleep difficulties between children with and without epilepsy. Databases were searched systematically, and studies identified in PubMed, EMBASE, PsychINFO and Medline. The meta-analysis included 19 studies comparing a total of 901 children with epilepsy to 1470 healthy children. Relative to healthy children, children with epilepsy experienced reduced sleep time, sleeping on average 34 mins less across self-report, actigraphy, 24-h video-EEG and polysomnography measures. They had more sleep difficulties specifically in the domains of night waking, parasomnias and sleep disordered breathing. The analysis also revealed a significantly increased percentage of N2 sleep and decreased sleep efficiency in children with epilepsy compared to healthy children. These results illustrate that children with epilepsy are vulnerable to more sleep difficulties compared to healthy children. This suggests that screening for sleep difficulties should be an integral part in a diagnosis of epilepsy to ensure that clinically relevant sleep difficulties are identified and treated. Such an approach may ultimately aid in the development of treatment strategies which can contribute to improvements in both developmental and diagnostic outcomes for children with epilepsy.
Topics: Adolescent; Child; Electroencephalography; Epilepsy; Humans; Polysomnography; Sleep; Sleep Apnea Syndromes
PubMed: 33561679
DOI: 10.1016/j.smrv.2021.101416 -
Epilepsia May 2024Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare developmental and epileptic encephalopathies associated with seizure and nonseizure symptoms. A... (Review)
Review
Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare developmental and epileptic encephalopathies associated with seizure and nonseizure symptoms. A comprehensive understanding of how many individuals are affected globally, the diagnostic journey they face, and the extent of mortality associated with these conditions is lacking. Here, we summarize and evaluate published data on the epidemiology of DS and LGS in terms of prevalence, incidence, diagnosis, genetic mutations, and mortality and sudden unexpected death in epilepsy (SUDEP) rates. The full study protocol is registered on PROSPERO (CRD42022316930). After screening 2172 deduplicated records, 91 unique records were included; 67 provided data on DS only, 17 provided data on LGS only, and seven provided data on both. Case definitions varied considerably across studies, particularly for LGS. Incidence and prevalence estimates per 100 000 individuals were generally higher for LGS than for DS (LGS: incidence proportion = 14.5-28, prevalence = 5.8-60.8; DS: incidence proportion = 2.2-6.5, prevalence = 1.2-6.5). Diagnostic delay was frequently reported for LGS, with a wider age range at diagnosis reported than for DS (DS, 1.6-9.2 years; LGS, 2-15 years). Genetic screening data were reported by 63 studies; all screened for SCN1A variants, and only one study specifically focused on individuals with LGS. Individuals with DS had a higher mortality estimate per 1000 person-years than individuals with LGS (DS, 15.84; LGS, 6.12) and a lower median age at death. SUDEP was the most frequently reported cause of death for individuals with DS. Only four studies reported mortality information for LGS, none of which included SUDEP. This systematic review highlights the paucity of epidemiological data available for DS and especially LGS, demonstrating the need for further research and adoption of standardized diagnostic criteria.
Topics: Humans; Lennox Gastaut Syndrome; Epilepsies, Myoclonic; Prevalence; Incidence; Sudden Unexpected Death in Epilepsy; Global Health
PubMed: 38252068
DOI: 10.1111/epi.17866 -
Epilepsy & Behavior : E&B Mar 2021A number of studies have suggested a pathophysiological link between allergic diseases and epilepsy. Understanding the association between allergic diseases and epilepsy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A number of studies have suggested a pathophysiological link between allergic diseases and epilepsy. Understanding the association between allergic diseases and epilepsy can help establish healthcare policies, implement prevention strategies, and provide a new direction for treatment. The study aimed to examine the association between allergic diseases and epilepsy.
METHODS
PubMed, EMBASE, and Web of Science were searched for relevant primary articles. Two individuals independently conducted abstract screening, full-text review, data extraction, and quality assessment. Random-effects models were used to pool the risk estimates.
RESULTS
From the 3124 citations identified, 32 were reviewed in full text. Finally, 11 studies with a total of 3,312,033 subjects were eligible for the analyses. Few studies reported the type of epilepsy, and there were inconsistent attempts to control for confounding. The pooled result showed that there was an 81% increase in the prevalence of epilepsy among individuals with asthma compared with those without asthma (odds ratio: 1.81, 95% confidence interval [CI]:1.47-2.21). The incidence of epilepsy in patients with eczema was 2.57 (95%CI: 1.54-4.27). Sensitivity analyses confirmed that no single study qualitatively influenced the pooled OR. All funnel plots were asymmetric upon visual inspection, suggesting publication bias.
CONCLUSION
Our findings suggest that patients with allergic diseases might have a high risk of epilepsy. Additional high-quality primary studies are required to confirm the association, obtain information regarding the mechanism of association, and determine prevention opportunities.
Topics: Epilepsy; Humans; Incidence; Odds Ratio; Prevalence
PubMed: 33556864
DOI: 10.1016/j.yebeh.2021.107770 -
CNS Drugs Jan 2024Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was reported in patients with amnestic mild cognitive impairment, schizophrenia, and Alzheimer's disease. However, the specific cognitive domains affected and the degree of evidence supporting these effects remain unclear. This systematic review and meta-analysis aimed to explore the effects of levetiracetam on different cognitive domains.
METHODS
This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We defined our inclusion criteria for the systematic review as: (1) randomized placebo-controlled trials (RCTs) involving human subjects, (2) double-blinded RCTs, and (3) RCTs evaluating the quantitative differences in cognitive function between levetiracetam and placebo. We excluded: (1) non-RCT studies, (2) open-label studies, and (3) RCTs lacking cognitive assessments for either intervention. Two authors independently searched electronic databases, including PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until 2 July 2023. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Meta-analytic techniques were applied to examine the impact of levetiracetam on cognitive domain tests, with Hedges' g facilitating the comparison with placebo. The domains analyzed comprised multi-domain, executive function, processing speed, working memory, verbal memory/learning (verbal ML), visuospatial memory/learning (visuospatial ML), and language. We used odds ratios to compare the incidence of treatment-emergent adverse events between the groups, including somnolence, fatigue, dizziness, headache, irritability, and cognitive adverse events.
RESULTS
A random-effects model was utilized to perform a meta-analysis of 16 RCTs including 545 participants. Compared with a placebo, levetiracetam was associated with improved executive function [Hedges'g = - 0.390, 95% confidence interval (CI) = - 0.609 to - 0.172, p < 0.001, I = 24.0%]. Subgroup analysis showed that levetiracetam outperformed placebo in patients without epilepsy (Hedges' g = - 0.419, 95% CI = - 0.647 to - 0.191, p < 0.001, I = 26.2%). Meanwhile, low-dose levetiracetam showed a moderate favorable effect over placebo (Hedges' g = -0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). In patients without epilepsy, low-dose levetiracetam was associated with improved executive function (Hedges'g = - 0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). Concurrently, levetiracetam was associated with more frequent somnolence than a placebo (odds ratio = 4.654, 95% CI = 1.533 to 14.124, p = 0.007, I = 32.9%). Potential publication bias was observed in the executive function domain.
CONCLUSIONS
This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution.
Topics: Humans; Cognition; Cognitive Dysfunction; Epilepsy; Levetiracetam; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 38102532
DOI: 10.1007/s40263-023-01058-9 -
Child's Nervous System : ChNS :... Mar 2023Drug-resistant epilepsy occurs in up to 30% of children suffering from seizures and about 10% qualify for surgical treatment. The aim of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Drug-resistant epilepsy occurs in up to 30% of children suffering from seizures and about 10% qualify for surgical treatment. The aim of this systematic review and meta-analysis is to analyze the potential benefit of early epilepsy surgery in children concerning primarily seizure and developmental outcome.
METHODS
PubMed and Embase databases were searched using a systematic search strategy to identify studies on pediatric epilepsy surgery under 3 years from their inception up to 2022. Outcome measures were seizure outcome, postoperative complications, seizure onset, and reduction rate of antiepileptic drugs. A meta-analysis was thereafter performed for all included cohort studies. A p-value of < 0.05 was considered as statistically significant.
RESULTS
A total of 532 patients were analyzed with 401 patients (75%) receiving resective or disconnective surgery under the age of 3 years and 80 patients (15%) receiving surgery older than 3 years. The remaining 51 patients (9%) underwent VNS implantation. Pooled outcome analysis for resective/disconnective surgery showed favorable outcome in 68% (95% CI [0.63; 0.73]), while comparative analysis between the age groups showed no significant difference (77% early group and 75% late group; RR 1.03, 95% CI [0.73; 1.46] p = 0.75). Favorable outcome for the VNS cohort was seen in 52%, 65% in the early and 45.1% in the late group (RR 1.4393, 95% CI [0.87; 2.4] z = 1.42, p = 0.16). Developmental outcome was improved in 26%. Morbidity rate was moderate and showed no significant difference comparing the age groups, and overall surgical mortality rate was very low (0.1%).
CONCLUSION
Epilepsy surgery in pediatric age, especially under the age of 3 years, is a feasible and safe way to treat intractable epilepsy. Further comparative studies of prospective nature, analyzing not only seizure but also developmental outcome, should be the focus of future studies.
Topics: Child; Humans; Child, Preschool; Prospective Studies; Epilepsy; Seizures; Drug Resistant Epilepsy; Anticonvulsants; Treatment Outcome
PubMed: 36219224
DOI: 10.1007/s00381-022-05699-x -
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 -
Dialogues in Clinical Neuroscience 2021Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better... (Review)
Review
Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better understanding of brain function, both normal and abnormal, throughout developmental stages. The degree to which childhood epilepsies exert a significant effect on brain network organisation and cognition remains unclear. The hypothesis suggests that the formation of abnormal networks associated with epileptogenesis early in life causes a disruption in normal brain network development and cognition, reflecting abnormalities in later life. Neurological diseases with onset during critical stages of brain maturation, including childhood epilepsy, may threaten this orderly neurodevelopmental process. According to the hypothesis that the formation of abnormal networks associated with epileptogenesis in early life causes a disruption in normal brain network development, it is then mandatory to perform a proper examination of children with new-onset epilepsy early in the disease course and a deep study of their brain network organisation over time. In regards, graph theoretical analysis could add more information. In order to facilitate further development of graph theory in childhood, we performed a systematic review to describe its application in functional dynamic connectivity using electroencephalographic (EEG) analysis, focussing on paediatric epilepsy.
Topics: Brain; Brain Mapping; Child; Cognition; Electroencephalography; Epilepsy; Humans; Magnetic Resonance Imaging; Nerve Net; Neurodevelopmental Disorders
PubMed: 35860177
DOI: 10.1080/19585969.2022.2043128 -
Epilepsy & Behavior : E&B May 2022Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has... (Review)
Review
Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has changed considerably, and a comprehensive systematic review of the contemporary literature is lacking. Here we synthesized published evidence on the occurrence of clinical impacts by age, the economic and humanistic (health-related quality-of-life [HRQoL]) burden, and health state utility. We provide an evidence-based, contemporary visualization of the clinical manifestations, highlighting that DS is not limited to seizures; non-seizure manifestations appear early in life and increase over time, contributing significantly to the economic and humanistic burden of disease. The primary drivers of HRQoL in DS include seizure severity, cognition, and motor and behavioral problems; in turn, these directly affect caregivers through the extent of assistance required and consequent impact on activities of daily living. Unsurprisingly, costs are driven by seizure-related events, hospitalizations, and in-home medical care visits. This systematic review highlights a paucity of longitudinal data; most studies meeting inclusion criteria were cross-sectional or had short follow-up. Nonetheless, available data illustrate the substantial impact on individuals, their families, and healthcare systems and establish the need for novel therapies to address the complex spectrum of DS manifestations.
Topics: Activities of Daily Living; Epilepsies, Myoclonic; Epileptic Syndromes; Humans; Seizures; Spasms, Infantile
PubMed: 35334258
DOI: 10.1016/j.yebeh.2022.108661