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Journal of Neurology Oct 2023The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and meta-analysis was to estimate the association between the extent of WML in CSVD and epilepsy, analyze whether these WML are associated with an increased risk of seizure recurrence, and evaluate if treatment with anti-seizure medication (ASM) is justified in first-seizure patients with WML and no cortical lesions.
METHODS
Following a pre-registered study protocol (PROSPERO-ID CRD42023390665), we systematically searched Pubmed and Embase for relevant literature comparing WML load between patients with epilepsy and controls as well as studies on seizure recurrence risk and ASM therapy in the presence vs. absence of WML. We calculated pooled estimates using a random effects model.
RESULTS
Eleven studies comprising 2983 patients were included in our study. Presence of WML (OR 2.14, 95% CI 1.38-3.33) and presence of relevant WML as assessed by visual rating scales (OR 3.96, 95% CI 2.55-6.16) but not WML volume (OR 1.30, 95% CI 0.91-1.85) were significantly associated with seizures. These results stayed robust in sensitivity analyses restricted to studies on patients with late-onset seizures/epilepsy. Only two studies assessed the association between WML and risk of seizure recurrence with conflicting results. Currently, there are no studies on the efficacy of ASM therapy in the presence of WML in CSVD.
CONCLUSIONS
This meta-analysis suggests an association between presence of WML in CSVD and seizures. More research is needed addressing the association between WML and risk of seizure recurrence and ASM therapy focusing on a population of patients with a first unprovoked seizure.
Topics: Humans; Anticonvulsants; White Matter; Epilepsy; Cerebral Small Vessel Diseases
PubMed: 37341807
DOI: 10.1007/s00415-023-11828-6 -
Neuropsychiatric Disease and Treatment 2023Stroke is one of the most frequent neurological syndromes in the adult population and the cause of 10% of all diagnosed epilepsies. It is attributed to the origin of up... (Review)
Review
BACKGROUND AND OBJECTIVE
Stroke is one of the most frequent neurological syndromes in the adult population and the cause of 10% of all diagnosed epilepsies. It is attributed to the origin of up to 50% of them in adults >60 years of age. Although a few risk factors have been described and considered when modeling predictive tools, this aspect is still clinically complex. The objective of this study is to describe and compare predictor scales of post stroke epilepsy (PSE) in adult patients with better performance.
METHODS
A systematic review and meta-analysis were performed of studies published between 2010 and 2020 and found in PubMed, Scopus, EMBASE, LILACS, BVS, Google Scholar, and CENTRAL databases. Sixteen studies were included with a total of 298,694 patients with a diagnosis of stroke, 5590 presented late seizures (LS).
RESULTS
Hemorrhage, cortical involvement, and early seizure were the elements most associated with the risk of presenting late seizures. The SeLECT score demonstrated a low risk of bias with a high predictive ability in patients with ischemic stroke (AUC: 0.77 [95% CI: 0.71-0.82]). In patients with hemorrhagic stroke, the CAVE score demonstrated adequate predictive ability (AUC: 0.81 [95% CI: 0.76-0.86]), but an uncertain risk of bias. Research has established risk factors for post ictal epilepsy; however, the numerous ways of assessing data in studies and the difference in their designs make the task of producing a predictive scale that covers the most important risk factors and is reliable for application in the clinical setting, regardless of stroke etiology, very arduous.
CONCLUSION
Hemorrhage, cortical involvement, and early seizure are associated with an increased risk of post ictal epilepsy. Also, elements such as age, traditional vascular risk factors, and functional assessment failed to reflect statistical significance. Finally, further research is required to refine the available predictive tools.
PubMed: 38161512
DOI: 10.2147/NDT.S439995 -
Seizure Apr 2024People with stigmatizing conditions associated with epilepsy encounter many difficulties in their daily lives and are more likely to have low self-esteem, low levels of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with stigmatizing conditions associated with epilepsy encounter many difficulties in their daily lives and are more likely to have low self-esteem, low levels of hope, internalize negative attitudes, decrease adherence to treatment, and experience unemployment. The purpose of this study was to quantify the extent of perceived stigma and self-stigma among people with epilepsy.
METHODOLOGY
This systematic review and meta-analysis followed the Preferred Reporting Item Review and Meta-analysis (PRISMA) guideline. PubMed, PsycINFO, Web of Science, Cochrane Library, Google Scholar, and HINARI were major search databases. The included literature reports the prevalence of perceived stigma and self-stigma among people with epilepsy in East Africa. The quality of each study was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data were extracted using a Microsoft Excel spreadsheet, and data analysis was performed using STATA version 11. The pooled prevalence of perceived stigma and self-stigma was determined using a random effect model. Heterogeneity between studies was checked using the I statistical test. Publication bias was checked using Egger's statistical test and funnel plot.
RESULTS
The pooled prevalence of perceived stigma and self-stigma in people with epilepsy was 43.9 % with a 95 % CI (29.2, 58.7) and 41.2 % with a 95 % CI (12.1, 70.3), respectively. Based on the country, sub-group analysis revealed that the prevalence of perceived stigma among people with epilepsy shows a notable difference between the countries. In Ethiopia, the prevalence was 51.8 % with a 95 % CI of 29.8 to 73.8; in Uganda, 39.4 % with a 95 % CI of 27.1 to 51.3; in Tanzania, 27.4 % with a 95 % CI of 27.9 to 36.9; and in Kenya, 33.2 % with a 95 % CI of 28.2 to 38.2.
CONCLUSION
Roughly 30 % of people with epilepsy experience self-stigma, while approximately 44 % of people with epilepsy experience perceived stigma. As a result, the relevant authorities ought to focus on reducing the prevalence of stigma among people who have epilepsy.
Topics: Humans; Epilepsy; Social Stigma; Self Concept; Africa, Eastern
PubMed: 38547570
DOI: 10.1016/j.seizure.2024.03.003 -
Neuro-oncology Advances 2024Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when...
BACKGROUND
Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials.
METHODS
Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative.
RESULTS
Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 = 33, phase 3 = 14. Common interventions included: Surgery = 13, radiotherapy = 8, and pharmacotherapy = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas.
CONCLUSIONS
Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials.
PubMed: 38596717
DOI: 10.1093/noajnl/vdae030 -
Orphanet Journal of Rare Diseases Sep 2023Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of genetic factors on disease progression has yet to be confirmed. We present a systematic review and meta-analysis of the known pathogenic variants to identify genotype-phenotype correlations.
METHODS
We collected all reported cases with genetically-confirmed LD containing data on disease history. Pathogenic variants were classified into missense (MS) and protein-truncating (PT). Three genotype classes were defined according to the combination of the variants: MS/MS, MS/PT, and PT/PT. Time-to-event analysis was performed to evaluate survival and loss of autonomy.
RESULTS
250 cases described in 70 articles were included. The mutated gene was NHLRC1 in 56% and EPM2A in 44% of cases. 114 pathogenic variants (67 EPM2A; 47 NHLRC1) were identified. The NHLRC1 genotype PT/PT was associated with shorter survival [HR 2.88; 95% CI 1.23-6.78] and a trend of higher probability of loss of autonomy [HR 2.03, 95% CI 0.75-5.56] at the multivariable Cox regression analysis. The population carrying the homozygous p.Asp146Asn variant of NHLRC1 genotype was confirmed to have a more favourable prognosis in terms of disease duration.
CONCLUSIONS
This study demonstrates the existence of prognostic genetic factors in LD, namely the genotype defined according to the functional impact of the pathogenic variants. Although the reasons why NHLRC1 genotype PT/PT is associated with a poorer prognosis have yet to be fully elucidated, it may be speculated that malin plays a pivotal role in LD pathogenesis.
Topics: Humans; Lafora Disease; Prognosis; Tandem Mass Spectrometry; Myoclonic Epilepsies, Progressive; Disease Progression; Ubiquitin-Protein Ligases
PubMed: 37658439
DOI: 10.1186/s13023-023-02880-6 -
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 -
Epilepsy & Behavior : E&B Dec 2023Anxiety and depression are common in adolescents with epilepsy. Identifying psychosocial risk factors for anxiety and depression is essential for adolescents with... (Review)
Review
Anxiety and depression are common in adolescents with epilepsy. Identifying psychosocial risk factors for anxiety and depression is essential for adolescents with epilepsy to receive appropriate support. This systematic review synthesised findings of studies examining the relationship between psychosocial factors and anxiety and/or depression in adolescents with epilepsy. Outcomes were anxiety, depression, and mixed anxiety & depression. Six electronic databases were searched for studies which: used cross-sectional or prospective designs; quantitatively evaluated the relationship between psychosocial factors and anxiety and/or depression; presented results for adolescents with epilepsy aged 9-18 years; and used validated measures of anxiety and/or depression. Psychosocial factors were categorised as intrapersonal, interpersonal, or parent-specific factors. Sixteen studies (23 articles) were included. All but one were cross-sectional. Regarding intrapersonal factors, alternative mental health difficulties were consistently positively associated with all three outcomes. Negative attitude towards epilepsy, lower seizure self-efficacy, lower self-esteem and stigma were consistently positively associated with depression. Interpersonal factors (i.e., lower family functioning assessed from an adolescent's perspective) and parent-specific factors (i.e., parental stigma, stress, anxiety and psychopathology) were positively associated with at least one outcome. Adolescent epilepsy management should exceed assessment of biological/biomedical factors and incorporate assessment of psychosocial risk factors. Prospective studies examining the interplay between biological/biomedical factors and the psychosocial factors underpinning anxiety and depression in adolescents with epilepsy are needed.
Topics: Humans; Adolescent; Depression; Prospective Studies; Anxiety; Anxiety Disorders; Epilepsy
PubMed: 38006843
DOI: 10.1016/j.yebeh.2023.109522 -
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 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 -
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