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Brain Imaging and Behavior Jun 2022Functional neuroimaging modalities have enhanced our understanding of juvenile myoclonic epilepsy (JME) underlying neural mechanisms. Due to its non-invasive, sensitive... (Review)
Review
Functional neuroimaging modalities have enhanced our understanding of juvenile myoclonic epilepsy (JME) underlying neural mechanisms. Due to its non-invasive, sensitive and analytical nature, functional magnetic resonance imaging (fMRI) provides valuable insights into relevant functional brain networks and their segregation and integration properties. We systematically reviewed the contribution of resting-state and task-based fMRI to the current understanding of the pathophysiology and the patterns of seizure propagation in JME Altogether, despite some discrepancies, functional findings suggest that corticothalamo-striato-cerebellar network along with default-mode network and salience network are the most affected networks in patients with JME. However, further studies are required to investigate the association between JME's main deficiencies, e.g., motor and cognitive deficiencies and fMRI findings. Moreover, simultaneous electroencephalography-fMRI (EEG-fMRI) studies indicate that alterations of these networks play a role in seizure modulation but fall short of identifying a causal relationship between altered functional properties and seizure propagation. This review highlights the complex pathophysiology of JME, which necessitates the design of more personalized diagnostic and therapeutic strategies in this group.
Topics: Brain; Electroencephalography; Humans; Magnetic Resonance Imaging; Myoclonic Epilepsy, Juvenile; Seizures
PubMed: 34786666
DOI: 10.1007/s11682-021-00595-5 -
Seizure Mar 2024To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence.
PURPOSE
To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence.
METHODS
Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy.
RESULTS
Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources.
SIGNIFICANCE
Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.
Topics: Humans; Epilepsy; Seizures; Genetic Testing; Mutation; Databases, Factual; Phenotype
PubMed: 37777370
DOI: 10.1016/j.seizure.2023.09.021 -
Epilepsia Oct 2023Febrile seizures affect 2%-5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained... (Review)
Review
Febrile seizures affect 2%-5% of U.S. children and are considered benign although associated with an increased risk of epilepsy and, rarely, with sudden unexplained death. We compared rates of mortality, neurodevelopmental disorders, and neuropathology in young children with simple and complex febrile seizures to healthy controls. We systematically reviewed studies of 3- to 72-month-old children with simple or complex febrile seizures ≤30 min. We searched studies with outcome measures on mortality, neurodevelopment, or neuropathology through July 18, 2022. Bias risk was assessed per study design. Each outcome measure was stratified by study design. PROSPERO registration is CRD42022361645. Twenty-six studies met criteria reporting mortality (11), neurodevelopment (11), and neuropathology (13), including 2665 children with febrile seizures and 1206 seizure-free controls. Study designs varied: 15 cohort, 2 cross-sectional, 3 case-control, 5 series, and 1 case report. Mortality outcomes showed stark contrasts. Six cohort studies following children after febrile seizure (n = 1348) reported no deaths, whereas four child death series and 1 case report identified 24.1% (108/449) deaths associated with simple (n = 104) and complex (n = 3) febrile seizures ≤30 min. Minor hippocampal histopathological anomalies were common in sudden deaths with or without febrile seizure history. Most electroencephalography (EEG) studies were normal. Neuroimaging studies suggested increased right hippocampal volumes. When present, neurodevelopmental problems usually preexisted febrile-seizure onset. Risk bias was medium or high in 95% (18/19) of cohort and case-control studies vs medium to low across remaining study designs. Research on outcomes after simple or brief complex febrile seizures is limited. Cohort studies suffered from inadequate sample size, bias risk, and limited follow-up durations to make valid conclusions on mortality, neurodevelopment, and neuropathology. Sudden death registries, focused on a very small percentage of all cases, strongly suggest that simple febrile seizures are associated with increased mortality. Although most children with febrile seizures have favorable outcomes, longer-term prospective studies are needed.
Topics: Child; Child, Preschool; Humans; Infant; Cohort Studies; Cross-Sectional Studies; Death, Sudden; Fever; Hippocampus; Seizures, Febrile
PubMed: 37466925
DOI: 10.1111/epi.17720 -
Epilepsia Oct 2020A fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing...
OBJECTIVE
A fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing seizure activity early in ictus must be removed to avoid postoperative recurrence of seizures is an area of ongoing research. Seizure spread dynamics in the initial seconds of ictus are often correlated with postoperative outcome; there is neither a consensus definition of early spread nor a concise summary of the existing literature linking seizure spread to postsurgical seizure outcomes. The present study is intended to summarize the literature that links seizure spread to postoperative seizure outcome and to provide a framework for quantitative assessment of early seizure spread.
METHODS
A systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Medline search identified clinical studies reporting data on seizure spread measured by intracranial electrodes, having at least 10 subjects and reporting at least 1-year postoperative outcome in the English literature from 1990 to 2019. Studies were evaluated regarding support for a primary hypothesis: Areas of early seizure spread represent cortex with seizure-generating potential.
RESULTS
The search yielded 4562 studies: 15 studies met inclusion criteria and 7 studies supported the primary hypothesis. The methods and metrics used to describe seizure spread were heterogenous. The timeframe of seizure spread associated with seizure outcome ranged from 1-14 seconds, with large, well-designed, retrospective studies pointing to 3-10 seconds as most likely to provide meaningful correlates of postoperative seizure freedom.
SIGNIFICANCE
The complex correlation between electrophysiologic seizure spread and the potential for seizure generation needs further elucidation. Prospective cohort studies or trials are needed to evaluate epilepsy surgery targeting cortex involved in the first 3-10 seconds of ictus.
Topics: Cerebral Cortex; Electrodes, Implanted; Electroencephalography; Epilepsy; Humans; Prospective Studies; Retrospective Studies; Seizures; Treatment Outcome
PubMed: 32944952
DOI: 10.1111/epi.16668 -
International Journal of Geriatric... Jul 2022Dementia and seizures often co-exist, but the association between these two disorders is not well established. Therefore, this systematic review and meta-analysis aimed... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Dementia and seizures often co-exist, but the association between these two disorders is not well established. Therefore, this systematic review and meta-analysis aimed to clarify the relationship between seizures and dementia.
METHODS
The PubMed, EMBASE, CBM, and CNKI databases were used to search for relevant publications from inception to August 25, 2021. Data extraction was performed by two authors independently. The random-effects model was adopted to evaluate the pooled estimates.
RESULTS
Two nested case-control studies and 18 cohort studies were included in the meta-analysis. Seizures were associated with the development of dementia and Alzheimer's disease (AD), and the pooled relative risk (RR) was 2.51 [95% confidence intervals (CI) = 1.87-3.36, p < 0.001] and 1.61 (95% CI = 1.42-1.82, p < 0.001), respectively. Pooled RR estimating the effect of dementia on seizures risk was 3.68 (95% CI = 3.05-4.44, p < 0.001). In addition, the pooled effect size of dementia on epilepsy risk was 3.02 (95% CI = 2.16-4.23, p < 0.001). The subgroup analyses suggested that vascular risk factors could confound the associations between these two disorders. Seizures might independently and significantly increase the risk of dementia, and in turn, dementia might predispose an individual to a higher risk of seizures.
CONCLUSIONS
These results suggested that dementia and seizures share common pathogenesis and might be treated with similar preventive treatment measures. Vascular changes in patients with dementia or seizures should also be examined.
Topics: Alzheimer Disease; Case-Control Studies; Cohort Studies; Humans; Risk Factors; Seizures
PubMed: 35726376
DOI: 10.1002/gps.5723 -
Seizure Nov 2022Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures.
METHODS
This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs.
RESULTS
From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I 15% and RR 2.79, 95% CI 1.58 to 4.93, I 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes.
CONCLUSION
This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.
Topics: Humans; Anticonvulsants; Treatment Outcome; Pyridones; Seizures; Epilepsy; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36206645
DOI: 10.1016/j.seizure.2022.09.020 -
Epilepsy & Behavior : E&B Mar 2024Epilepsy and dementia are bidirectional. The purpose of this review was to investigate the epidemiological characteristics of and to identify the risk factors for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epilepsy and dementia are bidirectional. The purpose of this review was to investigate the epidemiological characteristics of and to identify the risk factors for epilepsy in patients with dementia and dementia in patients with epilepsy.
METHODS
We retrieved the PubMed, Embase, Cochrane and Web of Science databases through January 2023. Two individuals screened the articles, extracted the data, and used a random effects model to pool the estimates and 95% confidence intervals (CIs).
RESULTS
From 3475 citations, 25 articles were included. The prevalence of seizures/epilepsy was 4% among dementia patients and 3% among Alzheimer's disease (AD) patients. For vascular dementia, Lewy body dementia, and frontotemporal dementia, the pooled period prevalence of seizures/epilepsy was 6%, 3%, and 2%, respectively. Baseline early-onset AD was associated with the highest risk of 5-year epilepsy (pooled hazard ratios: 4.06; 95% CI: 3.25-5.08). Dementia patients had a 2.29-fold greater risk of seizures/epilepsy than non-dementia patients (95% CI: 1.37-3.83). Moreover, for baseline epilepsy, the pooled prevalence of dementia was 17% (95% CI: 10-25%), and that of AD was 15% (95% CI: 9-21%). The pooled results suggested that epilepsy is associated with a greater risk of dementia (risk ratio: 2.83, 95% CI: 1.64-4.88).
CONCLUSIONS
There are still gaps in epidemiology regarding the correlation between dementia types and epilepsy, vascular risk factors, and the impact of antiseizure medication or cognitive improvement drugs on epilepsy and AD comorbidity.
Topics: Humans; Epilepsy; Alzheimer Disease; Lewy Body Disease; Comorbidity; Seizures
PubMed: 38301455
DOI: 10.1016/j.yebeh.2024.109640 -
Epilepsy Research Nov 2021Seizure clusters (SCs) are episodes of consecutive seizures that occur within a short period. The treatment patterns of rescue medications (RMs), as well as the burden... (Review)
Review
Seizure clusters (SCs) are episodes of consecutive seizures that occur within a short period. The treatment patterns of rescue medications (RMs), as well as the burden of SCs, have not been assessed. A systematic literature search on Embase.com (in PubMed and Embase), supplemented with keyword-based and bibliographic searches, identified 44 articles for disease burden, three treatment guidelines, and three articles for treatment patterns. Common SC definitions were ≥3 seizures/24 h, ≥2/24 h and ≥2/6 h. The rate of SCs in prospective studies ranged from 21.7 %-42.5 %. The frequency of status epilepticus (SE) was higher in SC patients. SCs were associated with higher seizure frequency, higher risk of treatment resistance, and lower likelihood of seizure remission. Quality of life (QoL) was lower in children with SCs than in those with isolated seizures. Seizure-related hospitalization was more common in SC than non-SC patients. SCs adversely affected the productivity of patients and their caregivers. In outpatients with SCs, RMs were prescribed to 24.6 %-89.6 % and utilized by 15.6 %-44.5 %, with rates being higher in children. Key reasons for RM under-utilization were lack of seizure action plans, poor physician-patient communication, and concerns with administration route. In conclusion, SCs are associated with a higher risk of SE, treatment resistance, and low rate of seizure remission. They adversely affect patient and caregiver QoL and work productivity. However, RMs are under-prescribed, and there is an urgent need to improve recognition of SCs, improve use of seizure action plans, and remove barriers to RM use.
Topics: Anticonvulsants; Child; Cost of Illness; Humans; Prevalence; Prospective Studies; Quality of Life; Risk Factors; Seizures
PubMed: 34521043
DOI: 10.1016/j.eplepsyres.2021.106748 -
Epilepsy & Behavior : E&B Sep 2022Academic skills, such as reading, spelling and arithmetic, are central to meaningful engagement with society throughout adolescence and into adulthood. The disruption... (Review)
Review
Academic skills, such as reading, spelling and arithmetic, are central to meaningful engagement with society throughout adolescence and into adulthood. The disruption caused by on-going seizure activity places children with drug-resistant epilepsy at a particularly high risk of poor academic attainment. Though epilepsy surgery during childhood has long-been associated with various cognitive changes, less is known of the extent to which pediatric epilepsy surgery impacts academic attainment. The aim of the present systematic review was to identify the nature of the effect of pediatric epilepsy surgery on the core academic skills of reading, writing, and arithmetic. The electronic databases Embase, Medline, PubMed, PsychInfo, OpenAire, and the ISRCTN registry were searched for studies examining academic attainment following epilepsy surgery in childhood, over the last three decades. Two thousand three-hundred and sixty-eight articles were screened for relevance. Thirteen studies met the inclusion criteria. Study quality and reliability were independently assessed by two reviewers. Results indicate that academic attainment primarily stabilizes in the first year following epilepsy surgery. Though changes to learning ability would not be expected in this early recovery phase, this review indicates that children do not, at least, lose the academic skills they have acquired before surgery. Postoperative declines in performance were most notably recorded in assessments of arithmetic, suggesting an area of potential vulnerability in this cohort. These declines were noted in cohorts with the longest periods between seizure onset and surgery. While older age at onset and seizure freedom correlated with improved academic attainment, further research is necessary to fully understand the specific effect of epilepsy surgery on academic attainment. Still, the present review provides valuable information regarding the likely academic outcomes in the early years following surgical treatment for drug-resistant epilepsy.
Topics: Adolescent; Adult; Child; Drug Resistant Epilepsy; Epilepsy; Humans; Mathematics; Reproducibility of Results; Seizures
PubMed: 35914437
DOI: 10.1016/j.yebeh.2022.108847 -
Neurology Feb 2020This systematic review and meta-analyses assessed seizure outcome following pediatric epilepsy surgery. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This systematic review and meta-analyses assessed seizure outcome following pediatric epilepsy surgery.
METHODS
MEDLINE, EMBASE, and Cochrane were searched for pediatric epilepsy surgery original research from 1990 to 2017. The outcome was seizure freedom at 12 months or longer follow-up. Using random-effects models, the effect sizes for controlled studies, uncontrolled studies on surgery locations (temporal lobe [TL], extratemporal lobe [ETL], or hemispheric surgery), pathologies, nonlesional epilepsy, and incomplete resection were estimated. Meta-regression assessed the relationship between age at surgery, age at seizure onset, and seizure outcome. Random-effects network meta-analysis was conducted for surgery locations.
RESULTS
Two hundred fifty-eight studies were included. Surgery achieved higher seizure freedom than medical therapy (odds ratio [OR] = 6.49 [95% confidence interval [CI]: 2.87-14.70], < 0.001). Seizure freedom declined over time after surgery, from 64.8% (95% CI: 51.2%-76.4%; = 0.034) at 1 year, to 60.3% (95% CI: 52.9%-67.4%; = 0.007) at 5 years, and to 39.7% (95% CI: 28.4%-52.2%, = 0.106) at 10 years. Seizure freedom was (1) highest for hemispheric surgery, followed by TL and ETL surgery, and (2) highest for tumor and lower for malformations of cortical development. Seizure freedom was lower for nonlesional than lesional epilepsy (OR = 0.54 [95% CI: 0.34, 0.88], = 0.013) and incomplete than complete resection (OR = 0.13 [95% CI: 0.08, 0.21], < 0.001). Age at surgery and age at seizure onset were associated with seizure freedom for mixed pathologies and surgery locations and TL surgery.
CONCLUSION
Epilepsy surgery was more effective than medical therapy to control seizures. Understanding seizure outcomes of different surgery locations, pathologies, nonlesional epilepsy, and incomplete resection will assist with presurgical counseling.
Topics: Child; Epilepsy; Humans; Seizures; Treatment Outcome
PubMed: 31996452
DOI: 10.1212/WNL.0000000000008966