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Frontiers in Neurology 2023The new antiseizure medications (ASMs) and non-invasive brain stimulation (NIBS) are controversial in controlling seizures. So, this network meta-analysis aimed to...
The efficacy and safety of third-generation antiseizure medications and non-invasive brain stimulation to treat refractory epilepsy: a systematic review and network meta-analysis study.
BACKGROUND
The new antiseizure medications (ASMs) and non-invasive brain stimulation (NIBS) are controversial in controlling seizures. So, this network meta-analysis aimed to evaluate the efficacy and safety of five third-generation ASMs and two NIBS therapies for the treatment of refractory epilepsy.
METHODS
We searched PubMed, EMBASE, Cochrane Library and Web of Science databases. Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM), perampanel (PER), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) were selected as additional treatments for refractory epilepsy in randomized controlled studies and other cohort studies. Randomized, double-blind, placebo-controlled, add-on studies that evaluated the efficacy or safety of medication and non-invasive brain stimulation and included patients with seizures were uncontrolled by one or more concomitant ASMs were identified. A random effects model was used to incorporate possible heterogeneity. The primary outcome was the change in seizure frequency from baseline, and secondary outcomes included the proportion of patients with ≥50% reduction in seizure frequency, and the rate of treatment-emergent adverse events.
RESULTS
Forty-five studies were analyzed. The five ASMs and two NIBS decreased seizure frequency from baseline compared with placebo. The 50% responder rates of the five antiseizure drugs were significantly higher than that of placebo, and the ASMs were associated with fewer adverse events than placebo ( < 0.05). The surface under the cumulative ranking analysis revealed that ESL was most effective in decreasing the seizure frequency from baseline, whereas CNB provided the best 50% responder rate. BRV was the best tolerated. No significant publication bias was identified for each outcome index.
CONCLUSION
The five third-generation ASMs were more effective in controlling seizures than placebo, among which CNB, ESL, and LCM were most effective, and BRV exhibited better safety. Although rTMS and tDCS did not reduce seizure frequency as effectively as the five drugs, their safety was confirmed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, https://www.crd.york.ac.uk/prospero/ (CRD42023441097).
PubMed: 38264091
DOI: 10.3389/fneur.2023.1307296 -
Innovations in Clinical Neuroscience 2023Compared to the general population, the risk of suicide is three times higher in patients with epilepsy and remains doubled for these patients even after adjusting for... (Review)
Review
OBJECTIVE
Compared to the general population, the risk of suicide is three times higher in patients with epilepsy and remains doubled for these patients even after adjusting for sociodemographic correlates of suicide in the absence of mental health comorbidities. Following the United States (US) Food and Drug Administration (FDA) alert prompting a black box warning regarding the association between suicidality and antiepileptic drugs (AEDs), several studies were conducted, the results of which have been ambiguous, with some demonstrating a positive association between suicidality and AEDs, while others did not. This systematic review of literature sought to study the relationship between suicidality and AEDs when used exclusively for treatment of epilepsy.
METHODS
A comprehensive literature search was conducted on PubMed without time limits using a predefined search language. The search results were then subjected to a systematic screening process. Eight out of a total of 443 articles satisfying predefined inclusion and exclusion criteria were included in the review for final data extraction.
RESULTS
Three studies found a significant association between suicide-related behavior and levetiracetam use in the treatment of epilepsy. One study reported a positive association of pregabalin use in patients with epilepsy under 40 years of age and high AED load with suicidality, independent of depression. The remaining four studies reported a significant association between positive family and personal history of psychiatric comorbidities and suicidality in epilepsy.
CONCLUSION
Although there were several methodological limitations, this review found an association between levetiracetam use and mental health comorbidities and the occurrence of suicidality in epilepsy. Larger prospective, randomized studies that overcome the limitations of current studies are required to provide definitive evidence on the occurrence of suicidality in patients with epilepsy and AED use.
PubMed: 37817817
DOI: No ID Found -
European Journal of Obstetrics,... Nov 2023Choroid plexus cysts (CPCs) are incidental findings on ultrasound examination of the fetal brain. It is not known if isolated CPCs are associated with any adverse health...
OBJECTIVES
Choroid plexus cysts (CPCs) are incidental findings on ultrasound examination of the fetal brain. It is not known if isolated CPCs are associated with any adverse health or neurodevelopmental outcomes during the life course. This systematic review aimed to collate and synthesize the evidence on whether or not isolated choroid plexus cysts are associated with an increased risk of adverse health or developmental outcomes during childhood and adolescence.
METHODS
A search strategy was developed specifically for this study and applied to four electronic databases Medline (Ovid), Embase (Ovid), Web of Science, and Google Scholar. Studies were assessed and selected for inclusion if there was a measurement of CPC (including single or multiple; unilateral or bilateral; isolated or presenting alongside other markers) during the antenatal or early neonatal period (<7 days) with follow-up of children and adolescents for health and developmental outcomes measured at any time from age 1 month onwards. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Due to heterogeneity in the types of outcome measures included and the timing of measurement of outcomes across the studies, it was not possible to pool data across studies and a narrative description of findings was presented.
RESULTS
Eight studies (three cohorts and five case series) met the inclusion criteria. Different methods were used for outcome assessment, such as in-person assessment, parent questionnaires, medical records, and telephone interviews with parents. Six studies measured outcomes only once during the specified duration of follow-up; two studies carried out paediatric reviews of the children several times during follow-up. There were no differences in developmental outcomes or physical health between babies with CPCs reported in the three cohort studies, and no abnormalities were detected in the children that were followed up in four of the five case series studies. Most of the included studies were graded as low quality due to the small sample size, high risk of selection bias, unclear definitions of CPC or lack of a comparison group.
CONCLUSIONS
The studies conducted to date do not provide evidence of adverse physical health outcomes or neurodevelopmental delays in babies with CPCs. However, most of these studies were small and included a narrow range of outcomes. Further research is needed to explore the relative incidence of outcomes such as ASD, ADHD, epilepsy and educational attainment in children with CPCs.
Topics: Infant; Infant, Newborn; Child; Humans; Female; Adolescent; Pregnancy; Choroid Plexus; Cohort Studies; Ultrasonography; Parents; Cysts
PubMed: 37778251
DOI: 10.1016/j.ejogrb.2023.09.013 -
Journal of Education and Health... 2023Epilepsy is the most common chronic neurologic disease which is characterized by recurrent attacks of headache after seizure. Researches show that self-management is an... (Review)
Review
Epilepsy is the most common chronic neurologic disease which is characterized by recurrent attacks of headache after seizure. Researches show that self-management is an important factor in improving the quality of life and quality of care of people affected by epilepsy. Mobile phone technologies play a potential role in patient care assistance and treatment of epilepsy. This systematic review was conducted with an aim to study the role of mobile health in the management of epilepsy. This study was conducted by searching databases such as PubMed, Scopus, Web of Science, and Google scholar search engines using the following keywords: "m-health," "mobile health," "Telemedicine," "Mobile Application," "Smartphone," "epilepsy," and "epilepsy management." Articles published from January 1, 1990 to September 1, 2021 were searched. Inclusion criteria included all articles published in English with a focus on the role of mHealth in the management of epilepsy. Review articles and studies that were not about patients were omitted. In this study, of a total of 4225 retrieved articles, 10 studies met the full-text inclusion criteria. Three types of researches (30%) were done in the USA, five studies (50%) were conducted as randomized controlled trials, and eight articles (80%) had the highest quality. Among the considered articles, three articles (30%) were engaged in training users in epilepsy management. Five articles (50%) reported improvement in seizure control in patients with epilepsy and two articles (20%) did not report any significant improvement. Mobile technologies have a promising role in providing health assessment, education, and other services for patients, and they also help in controlling seizures attack and improvement of epilepsy management. These technologies enjoy great attractiveness, and utilizing them will lead to patient satisfaction.
PubMed: 38023071
DOI: 10.4103/jehp.jehp_1188_22 -
Frontiers in Neurology 2023Epidemiological studies have demonstrated a comorbid association between migraine and epilepsy. However, despite the long history of this association, the exact nature...
BACKGROUND
Epidemiological studies have demonstrated a comorbid association between migraine and epilepsy. However, despite the long history of this association, the exact nature of the relationship between migraine and epilepsy remains largely unresolved. Therefore, it is crucial to conduct a meta-analysis in order to thoroughly investigate the relationship between migraine and epilepsy.
METHODS
Odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs) regarding association between migraine and epilepsy were summarized using STATA 12.0 software.
RESULTS
There was an 80% increase in the lifetime prevalence of migraine among patients with epilepsy, compared to those without epilepsy with a random effects model (OR/RR: 1.80, 95% CI: 1.35 to 2.40, I = 97.5%, < 0.001). There was an 80% increase in the lifetime prevalence of epilepsy among patients with migraine, compared to those without migraine with a random effects model (OR/RR: 1.80, 95% CI: 1.43 to 2.25, I = 80.6%, < 0.001).
CONCLUSIONS
It is important to note the comorbid association between migraine and epilepsy examined in the study.
PubMed: 38249732
DOI: 10.3389/fneur.2023.1276663 -
Epilepsy & Behavior : E&B Aug 2023Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects....
Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).
INTRODUCTION
Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders.
PURPOSE
The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology.
METHODS
A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology.
RESULTS
DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence.
CONCLUSIONS
Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.
Topics: Adult; Humans; Spain; Drug Resistant Epilepsy; Epilepsy; Treatment Outcome; Decision Support Techniques; Anticonvulsants
PubMed: 37480633
DOI: 10.1016/j.yebeh.2023.109350 -
Antioxidants (Basel, Switzerland) Jul 2023Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase... (Review)
Review
Antioxidant Therapy Reduces Oxidative Stress, Restores Na,K-ATPase Function and Induces Neuroprotection in Rodent Models of Seizure and Epilepsy: A Systematic Review and Meta-Analysis.
Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase activity and oxidative stress participation. We conducted this study to investigate the impact of antioxidant therapy on oxidative stress, Na,K-ATPase activity, seizure factors, and mortality in rodent seizure/epilepsy models induced by pentylenetetrazol (PTZ), pilocarpine (PILO), and kainic acid (KA). After screening 561 records in the MEDLINE, EMBASE, Web of Science, Science Direct, and Scopus databases, 22 were included in the systematic review following the PRISMA guidelines. The meta-analysis included 14 studies and showed that in epileptic animals there was an increase in the oxidizing agents nitric oxide (NO) and malondialdehyde (MDA), with a reduction in endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase (SO). The Na,K-ATPase activity was reduced in all areas evaluated. Antioxidant therapy reversed all of these parameters altered by seizure or epilepsy induction. In addition, there was a percentage decrease in the number of seizures and mortality, and a meta-analysis showed a longer seizure latency in animals using antioxidant therapy. Thus, this study suggests that the use of antioxidants promotes neuroprotective effects and mitigates the effects of epilepsy. The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO) CRD42022356960.
PubMed: 37507936
DOI: 10.3390/antiox12071397 -
Epilepsy & Behavior : E&B Apr 2024Children and young people with epilepsy are at higher risk of mental health disorders and atypical neurodevelopmental outcomes compared to the general population. It is... (Review)
Review
Children and young people with epilepsy are at higher risk of mental health disorders and atypical neurodevelopmental outcomes compared to the general population. It is essential to detect such comorbidities early in children with epilepsy and provide appropriate interventions, to improve clinical outcomes. We aimed to identify and evaluate the measurement properties of Patient-Reported Outcome Measures (PROMs) that have been validated specifically to measure mental health and neurodevelopmental outcomes in children and/or young people with epilepsy. We searched Embase, Medline, and PsycINFO in May 2023 for relevant studies. Mental health was defined as psychological symptoms (e.g., anxiety, depression, psychosis) and/or behavioural difficulties (e.g., conduct disorders). Neurodevelopmental outcomes included neurodevelopmental disorder traits such as attention-deficit hyperactivity disorder (ADHD) and autistic spectrum disorders. We assessed methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidance. Twelve papers were identified that psychometrically evaluated 13 relevant PROMs (two epilepsy-specific, eleven generic). The appraisal of the PROMs was limited by the availability of only one or two published articles for each, and incomplete psychometric evaluations in some cases. The tool demonstrating the strongest evidence was The Neurological Disorders Depression Inventory-Epilepsy for Youth. The ADHD Rating Scale-IV and The Paediatric Symptom Checklist -17 demonstrated good evidence in favour of at least two measurement properties. This review identified only a small number of mental health and neurodevelopmental PROMs evaluated specifically in paediatric epilepsy. There is a need for further validation of mental health and neurodevelopmental PROMs in children with epilepsy.
Topics: Adolescent; Humans; Child; Mental Health; Psychotic Disorders; Epilepsy; Anxiety Disorders; Patient Reported Outcome Measures; Quality of Life
PubMed: 38368788
DOI: 10.1016/j.yebeh.2024.109671 -
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