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Epilepsy & Behavior : E&B May 2024In recent years, adjunctive therapies for epilepsy management are being explored due to considerable side effects carried by antiepileptic drugs (AEDs) and widespread... (Review)
Review
OBJECTIVES
In recent years, adjunctive therapies for epilepsy management are being explored due to considerable side effects carried by antiepileptic drugs (AEDs) and widespread reports of drug-resistant epilepsy. One such approach is non-invasive musical neurostimulation. Within this context, Mozart's sonata K448 has received particular attention following reports of reduced seizure frequency and a decrease in epileptiform discharges during and after music exposure; often described as the 'Mozart effect'. However, controversy exists around the effectiveness of K448 in epilepsy and the strength and quality of the evidence supporting it. Therefore, this study aims to systematically review the available literature around the Mozart effect, in both adult and paediatric cases of epilepsy.
METHODS
We carried out a literature search on PubMed, Science Direct, Scopus and Web of Science using the query string ALL= (Mozart AND epileps*). Selected clinical studies were classified based on the age of the population studied, as paediatric (0-18 years), adult (19 years or older) or a combination of the two. All the studies were evaluated using the Johns Hopkins Nursing Evidence-Based Practice (JHNEBP) rating scale to determine the strength of the evidence (level) and the quality of the research evidence.
RESULTS
Out of 538 records, 25 studies were selected, grouped based on the age of the population studied and evaluated using the JHNEBP rating scale. Ten level 1 studies, which represent the strongest evidence, were identified, including six RCTs and three meta-analyses. Nine of these ten studies show a decrease in epileptiform discharges and in seizure frequency following exposure to Mozart's K448. One multiverse analysis reported lack of statistically significant evidence to support the use of K448 in epilepsy or any other medical condition.
CONCLUSIONS
A growing body of evidence supports the Mozart effect on epilepsy, with notable studies including RCTs and comprehensive meta-analyses. This review identified nine level 1 studies, conducted by research groups worldwide, which endorse the use of Mozart's music to reduce seizures and epileptiform discharges in adult and paediatric epilepsy patients. However, existing research exhibits limitations like varying protocols, small sample sizes and diverse treatment regimens. Additionally, studies that combine adult and paediatric patients fail to take account of developmental differences between these two groups - particularly with regards to brain maturation and neurophysiology - which could negatively impact upon the accuracy of findings by obscuring important age-related differences in response to intervention. Adequately addressing these limitations will be crucial to demonstrating proof of concept; otherwise, a potentially valuable, non-invasive, accessible, and affordable therapeutic option for drug-resistant epilepsy will remain on the medical fringe. Further research with larger samples and stricter protocols, particularly considering patient age and drug regimens, is required.
Topics: Humans; Drug Resistant Epilepsy; Music Therapy; Child; Adult; Adolescent; Child, Preschool
PubMed: 38636110
DOI: 10.1016/j.yebeh.2024.109743 -
Seizure May 2024
Review
Topics: Humans; Epilepsy; Pregnancy; Female; Pregnancy Complications; Health Personnel; Health Services Accessibility
PubMed: 38631244
DOI: 10.1016/j.seizure.2024.04.007 -
Nutrition Research (New York, N.Y.) Jun 2024Treatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies... (Review)
Review
Treatment adherence, defined as the degree to which the patient actively follows the plan of care, is very difficult for subjects undergoing ketogenic dietary therapies (KDTs). This is a relevant issue because adherence to dietary therapies is considered 1 of the primary determinants of the treatment's success. This paper aimed to review the literature evidence about KDT adherence according to age and diagnosis of patients. Performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this systematic review included clinical trials and observational studies. The risk of bias was assessed by the RoB 2.0 Cochrane tool and the quality of evidence according to the Mixed Methods Appraisal Tool system. Twenty-two articles were included, with more than half (n = 12) having average quality (2-3 stars). The studies' heterogeneity in measuring adherence and diagnosis made it difficult to compare results. Mean adherence rates were 71.5%, 66%, and 63.9% for children, adolescents, and adults, respectively. Adherence and compliance rates varied according to the follow-up period (79.7%, 66.7%, and 37.7% at 6, 24, and 36 months, respectively). The most frequent reasons for low adherence were linked to inefficacy in seizure control, adverse effects, food refusal, difficulty in preparing KDT meals or diet restrictiveness, lack of motivation, poor parental compliance, or cost of the diet. To conclude, there is a lack of standardized tools to measure adherence. Several studies highlighted the families' challenges in adhering to KDTs. These factors should be considered when creating strategies and resources on family education.
Topics: Humans; Diet, Ketogenic; Epilepsy; Patient Compliance; Child; Adolescent; Adult
PubMed: 38631175
DOI: 10.1016/j.nutres.2024.03.009 -
Frontiers in Neurology 2024Epilepsy is one of the most common serious chronic neurological disorders, which can have a serious negative impact on individuals, families and society, and even death....
BACKGROUND
Epilepsy is one of the most common serious chronic neurological disorders, which can have a serious negative impact on individuals, families and society, and even death. With the increasing application of machine learning techniques in medicine in recent years, the integration of machine learning with epilepsy has received close attention, and machine learning has the potential to provide reliable and optimal performance for clinical diagnosis, prediction, and precision medicine in epilepsy through the use of various types of mathematical algorithms, and promises to make better parallel advances. However, no bibliometric assessment has been conducted to evaluate the scientific progress in this area. Therefore, this study aims to visually analyze the trend of the current state of research related to the application of machine learning in epilepsy through bibliometrics and visualization.
METHODS
Relevant articles and reviews were searched for 2004-2023 using Web of Science Core Collection database, and bibliometric analyses and visualizations were performed in VOSviewer, CiteSpace, and Bibliometrix (R-Tool of R-Studio).
RESULTS
A total of 1,284 papers related to machine learning in epilepsy were retrieved from the Wo SCC database. The number of papers shows an increasing trend year by year. These papers were mainly from 1,957 organizations in 87 countries/regions, with the majority from the United States and China. The journal with the highest number of published papers is EPILEPSIA. Acharya, U. Rajendra (Ngee Ann Polytechnic, Singapore) is the authoritative author in the field and his paper "Deep Convolutional Neural Networks for Automated Detection and Diagnosis of Epileptic Seizures Using EEG Signals" was the most cited. Literature and keyword analysis shows that seizure prediction, epilepsy management and epilepsy neuroimaging are current research hotspots and developments.
CONCLUSIONS
This study is the first to use bibliometric methods to visualize and analyze research in areas related to the application of machine learning in epilepsy, revealing research trends and frontiers in the field. This information will provide a useful reference for epilepsy researchers focusing on machine learning.
PubMed: 38628694
DOI: 10.3389/fneur.2024.1374443 -
Seizure Apr 2024Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side. (Review)
Review
BACKGROUND
Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side.
OBJECTIVE
The present study aims to systematically review the literature on RS-VNS, assessing its effectiveness and safety.
METHODS
A systematic review following PRISMA guidelines was conducted: Pubmed/MEDLINE, The Cochrane Library, Scopus, Embase and Web of science databases were searched from inception to August 13th,2023. Gray literature was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy.
RESULTS
Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively).
CONCLUSION
Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients.
Topics: Humans; Vagus Nerve Stimulation; Drug Resistant Epilepsy
PubMed: 38615369
DOI: 10.1016/j.seizure.2024.02.011 -
Translational Psychiatry Apr 2024Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations;...
Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.
Topics: Mice; Humans; Rats; Animals; Deep Brain Stimulation; Rodentia; Brain; Epilepsy; Hippocampus
PubMed: 38605027
DOI: 10.1038/s41398-023-02727-5 -
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 -
Neuro-oncology Advances 2024The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous...
BACKGROUND
The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies.
METHODS
A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated 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-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective = 27 and prospective = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas.
CONCLUSIONS
Outcome measurement across observational studies of incidental and untreated intracranial meningioma 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 observational studies.
PubMed: 38596715
DOI: 10.1093/noajnl/vdae042 -
PloS One 2024Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients.
MATERIAL AND METHODS
The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis.
RESULTS
A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity.
CONCLUSION
In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.
Topics: Adolescent; Humans; Child; Myoclonic Epilepsy, Juvenile; Epilepsy, Absence; Seizures; Drug Resistant Epilepsy; Risk Factors; Electroencephalography; Anticonvulsants
PubMed: 38593118
DOI: 10.1371/journal.pone.0300930 -
Frontiers in Neurology 2024Several clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS)....
OBJECTIVE
Several clinical trials have suggested that fenfluramine (FFA) is effective for the treatment of epilepsy in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). However, the exploration of its optimal target dose is ongoing. This study aimed to summarize the best evidence to inform this clinical issue.
MATERIALS AND METHODS
We searched PubMed, Embase (via Ovid), and Web of Science for relevant literature published before December 1st, 2023. Randomized, double-blind, placebo-controlled studies that evaluated the efficacy, safety, and tolerability of FFA in DS and LGS were identified and meta-analysis was performed according to doses. The study was registered with PROSPERO (CRD42023392454).
RESULTS
Six hundred and twelve patients from four randomized controlled trials were enrolled. The results demonstrated that FFA at 0.2, 0.4, or 0.7 mg/kg/d showed significantly greater efficacy compared to placebo in terms of at least 50% reduction ( < 0.001, < 0.001, < 0.001) and at least 75% reduction ( < 0.001, = 0.007, < 0.001) in monthly seizure frequency from baseline. Moreover, significantly more patients receiving FFA than placebo were rated as much improved or very much improved in CGI-I by both caregivers/parents and investigators ( < 0.001). The most common treatment-emergent adverse events were decreased appetite, diarrhea, fatigue, and weight loss, with no valvular heart disease or pulmonary hypertension observed in any participant. For dose comparison, 0.7 mg/kg/d group presented higher efficacy on at least 75% reduction in seizure ( = 0.006) but not on at least 50% reduction. Weight loss ( = 0.002), decreased appetite ( = 0.04), and all-cause withdrawal ( = 0.036) were more common in 0.7 mg/kg/d group than 0.2 mg/kg/d. There was no statistical difference in other safety parameters between these two groups.
CONCLUSION
The higher range of the licensed dose achieves the optimal balance between efficacy, safety, and tolerability in patients with DS and LGS.
CLINICAL TRIAL REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023392454.
PubMed: 38590719
DOI: 10.3389/fneur.2024.1371704