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Epilepsy Research May 2024Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term... (Meta-Analysis)
Meta-Analysis
Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation.
Topics: Humans; Deep Brain Stimulation; Electrodes, Implanted; Electroencephalography; Seizures
PubMed: 38564925
DOI: 10.1016/j.eplepsyres.2024.107356 -
Neurology May 2024High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups.
METHODS
We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022. We defined favorable surgical outcome (FSO) as Engel class I, International League Against Epilepsy class 1, or seizure-free status. The prognostic value of crHFOs-area for FSO was assessed by (1) the pooled FSO proportion after crHFOs-area; (2) FSO for crHFOs-area vs without crHFOs-area; and (3) the predictive performance. We defined high combined prognostic value as FSO proportion >80% + FSO crHFOs-area >without crHFOs-area + area under the curve (AUC) >0.75 and examined this for the clinical subgroups (study design, age, diagnostic type, HFOs-identification method, HFOs-rate thresholding, and iEEG state). Temporal lobe epilepsy (TLE) was compared with extra-TLE through dichotomous variable analysis. Individual patient analysis was performed for sex, affected hemisphere, MRI findings, surgery location, and pathology.
RESULTS
Of 1,387 studies screened, 31 studies (703 patients) met our eligibility criteria. Twenty-seven studies (602 patients) analyzed FRs and 20 studies (424 patients) ripples. Pooled FSO proportion after crHFOs-area was 81% (95% CI 76%-86%) for FRs and 82% (73%-89%) for ripples. Patients with crHFOs-area achieved more often FSO than those without crHFOs-area (FRs odds ratio [OR] 6.38, 4.03-10.09, < 0.001; ripples 4.04, 2.32-7.04, < 0.001). The pooled AUCs were 0.81 (0.77-0.84) for FRs and 0.76 (0.72-0.79) for ripples. Combined prognostic value was high in 10 subgroups: retrospective, children, long-term iEEG, threshold (FRs and ripples) and automated detection and interictal (FRs). FSO after complete resection of FRs-area (crFRs-area) was achieved less often in people with TLE than extra-TLE (OR 0.37, 0.15-0.89, = 0.006). Individual patient analyses showed that crFRs-area was seen more in patients with FSO with than without MRI lesions ( = 0.02 after multiple correction).
DISCUSSION
Complete resection of the brain area with HFOs is associated with good postsurgical outcome. Its prognostic value holds, especially for FRs, for various subgroups. The use of HFOs for extra-TLE patients requires further evidence.
Topics: Child; Humans; Electrocorticography; Prognosis; Electroencephalography; Retrospective Studies; Epilepsy; Epilepsy, Temporal Lobe
PubMed: 38560817
DOI: 10.1212/WNL.0000000000209216 -
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 -
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 -
Cureus Feb 2024Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population.... (Review)
Review
Epilepsy, a widespread neurological disorder characterized by recurrent seizures, affects millions globally, with a significant impact on the pediatric population. Antiepileptic drugs (AEDs) constitute the primary treatment; however, drug-resistant epilepsy (DRE), especially in children, poses a therapeutic challenge. Alternative interventions, such as surgery, vagus nerve stimulation, and the ketogenic diet (KD), have been explored. This systematic review aims to investigate various types of KDs, their distinctions, their effectiveness, and their safety concerning the reduction of seizure frequency, achieving seizure freedom, and the occurrence of adverse events. The study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search was conducted using databases such as PubMed Central (PMC), MedLine, and Science Direct to identify relevant articles. Eligibility criteria and quality assessment tools were applied to evaluate the potential risk of bias and select 11 articles for inclusion in this review. The selected articles encompassed four randomized controlled trials (RCTs), two systematic reviews, and five narrative reviews. The data collected for this review was completed on October 2, 2023. Challenges, such as palatability, cultural factors, and adherence difficulties, were identified. Family or caregiver involvement plays a pivotal role in treatment success. Despite numerous RCTs and reviews, information gaps persist, hindering conclusive outcomes. Evaluating the risk-benefit ratio is crucial, considering potential side effects. The highly individualized nature of KD therapy, influenced by diverse seizure types and syndromes, necessitates a trial-and-error approach monitored by a multidisciplinary team. Long-term safety and efficacy demand continuous real-life patient data review. In summary, while KD presents a promising alternative for DRE, its success relies on meticulous planning, individualized implementation, and ongoing research to address existing challenges and information gaps.
PubMed: 38533170
DOI: 10.7759/cureus.54863 -
Cureus Feb 2024Low medication adherence remains a major challenge in the treatment of epilepsy, particularly in children. In recent years, several approaches and interventions have... (Review)
Review
Low medication adherence remains a major challenge in the treatment of epilepsy, particularly in children. In recent years, several approaches and interventions have been employed to promote medication adherence in children with epilepsy (CWE). In this study, we aimed to summarize the evidence on these interventions. In this systematic review, major medical electronic databases were searched for relevant literature from January 2005 till July 2023, including PsycINFO, Medline (via PubMed), Google Scholar, Taylor & Francis databases, and CENTRAL by the Cochrane Library. We planned to include observational studies (with a control arm) and clinical trials involving children/adolescents (<19 years) with epilepsy and/or their caregivers/families who underwent any intervention to improve adherence to anti-seizure medications. Out of 536 articles searched, eight (six randomized trials and two non-randomized intervention studies) were included in the systematic review. A total of 2,685 children/adolescents along with their caregivers participated in these studies. Six studies used educational and two used behavioral interventions to improve adherence to anti-seizure medications. Four studies showed variable levels of adherence improvement, ranging from 2-20% up to 73.9% post-intervention. To conclude, the findings suggest the potential for educational interventions to promote medication adherence in CWE. The class of evidence was II to III among the included studies, as per American Academy of Neurology guidelines.
PubMed: 38523977
DOI: 10.7759/cureus.54680 -
Cureus Feb 2024This meta-analysis aimed to assess the all-cause mortality and cardiovascular outcomes among patients diagnosed with epilepsy. The entire process of this systematic... (Review)
Review
This meta-analysis aimed to assess the all-cause mortality and cardiovascular outcomes among patients diagnosed with epilepsy. The entire process of this systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency and reporting completeness. A comprehensive search strategy was employed to identify relevant studies in electronic databases, including PubMed, Embase, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL), from January 1, 2010, to January 15, 2024. Outcomes assessed in this meta-analysis included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and arrhythmias. A total of 12 studies were included in this meta-analysis with a pooled sample size of 7,026,313. The majority of included studies were conducted in Taiwan (n=4). Our study revealed that individuals with epilepsy faced a higher risk of all-cause mortality, cardiovascular mortality, and stroke. Although there was a higher incidence of myocardial infarction and arrhythmias among epilepsy patients, this disparity did not reach statistical significance. There is a need for future research to explore the impact of epilepsy types, antiepileptic drugs, and lifestyle factors on cardiovascular outcomes.
PubMed: 38523952
DOI: 10.7759/cureus.54706 -
Frontiers in Neurology 2024Depression is a major public health problem and negatively affects the quality of life of patients with epilepsy. Despite multiple studies investigating the magnitude...
BACKGROUND
Depression is a major public health problem and negatively affects the quality of life of patients with epilepsy. Despite multiple studies investigating the magnitude and predictors, the results have been inconsistent. Therefore, this study aimed to estimate the pooled prevalence and factors associated with depressive symptoms among patients with epilepsy in Ethiopia.
METHODS
The primary articles were searched using databases like PubMed, Google Scholar, CINAHL, SCOPUS, EMBASE, and African Journal Online. A total of 10 primary articles that assessed the prevalence and factors associated with depressive symptoms among patients with epilepsy in Ethiopia were included. A Microsoft Excel spreadsheet was used to extract the data, which was then exported to Stata version 14 for further analysis. The statistical heterogeneity was evaluated using the test. Due to heterogeneity, a random effect meta-analysis model was employed. Publication bias was checked through Egger's weighted regression test and funnel plot.
RESULTS
A total of 10 primary studies with 3,532 participants were included. The pooled prevalence of depressive symptoms among patients with epilepsy was found to be 41.69% (95% CI, 37.70, 45.68). The pooled prevalence of depressive symptoms was 48.61, 42.98, 40.68, 38.27, and 34.80% in Oromia, SNNPs, Amhara, Addis Ababa, and Tigray, respectively, based on a sub-group analysis per regional state. Perceived stigma (AOR = 3.30, 95% CI: 1.40, 7.80), seizure frequency (AOR = 3.81, 95% CI: 1.03, 14.09), and perceived stress (AOR = 4.6, 95% CI: 1.05, 20.06) were factors associated with depressive symptoms.
CONCLUSION
We found that depressive symptoms affects at least four out of ten patients with epilepsy, indicating an immense burden. Depressive symptoms were extremely prevalent in those who had high levels of stigma, a monthly seizure frequency of once or more, and perceived stress. Therefore, physicians should take extra precautions when treating patients with epilepsy who have certain conditions.
SYSTEMATIC REVIEW REGISTRATION
This study was registered according to The International Prospective Register of Systemic Review (PROSPERO) with the registration ID (CRD42023484308).
PubMed: 38500809
DOI: 10.3389/fneur.2024.1352648 -
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 -
European Journal of Medical Research Mar 2024Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of... (Review)
Review
BACKGROUND
Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients.
METHODS
The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here.
RESULTS
The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures.
CONCLUSIONS
Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.
Topics: Adult; Humans; Leukodystrophy, Metachromatic; Quality of Life; Cost of Illness
PubMed: 38494502
DOI: 10.1186/s40001-024-01771-1