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Seizure Oct 2021Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated antibodies, and AE-related seizures are still unclear.
AIMS
This research evaluated the relationship between AE, AE-related seizures, and neuronal antibodies, as well as the morbidity of AE with early incidence.
METHODS
The PubMed, Embase, Cochrane, and Web of Science databases were searched. Pooled estimates and 95% confidence intervals (CIs) were calculated using a random-effects model.
RESULTS
Of the 4,869 citations identified, 100 articles were reviewed in full, and 42 subgroups were analyzed. The overall incidence of AE patients with seizures was 42% (95% CI: 0.40-0.44), and among them, the incidence of epilepsy in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients was 73% (95% CI: 0.70-0.77). Subsequently, we found that the prevalence of AE as the cause of epilepsy within the pooled period was 1% (95% CI: 0.01-0.02), while the overall positive rate of neuronal antibodies in epilepsy patients was 4% (95% CI: 0.03-0.05). Additionally, the detection rates of different antibodies among epilepsy patients were as follows: anti-NMDAR, 1%; anti-leucine-rich glioma inactivated 1 (LGI1), 1%; anti-contactin-associated protein-like 2 (CASPR2), 2%.
CONCLUSION
Based on our findings, neuronal antibodies may serve as a bridge to study AE and immune-related epilepsy. To further understand the differences in outcomes following different treatment measures, and to provide more information for public health policy and prevention, more research is needed to improve the accuracy of estimations.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Encephalitis; Epilepsy; Hashimoto Disease; Humans
PubMed: 34284303
DOI: 10.1016/j.seizure.2021.07.005 -
Neurological Sciences : Official... Sep 2023Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common... (Review)
Review
BACKGROUND AND AIMS
Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%). To date, 44 patients with FDXR mutations have been reported. We describe here on two new patients, siblings, who presented with a quite different phenotype compared to previously described patients.
METHODS
Clinical, neurophysiological, and genetic features of two siblings and a systematic literature review focused on the clinical spectrum of the disease are described.
RESULTS
Both patients presented with an acute-sub-acute onset of peripheral neuropathy and only in later stages of the disease developed the typical features of FDXR-associated disease.
INTERPRETATION
The peculiar clinical presentation at onset and the evolution of the disease in our patients and in some cases revised from the literature shed lights on a new possible phenotype of FDXR-associated disease: a peripheral neuropathy which can mimic an acute inflammatory disease.
Topics: Humans; Ataxia; Cerebellar Ataxia; Diagnosis, Differential; Mutation; Peripheral Nervous System Diseases; Phenotype; Ferredoxin-NADP Reductase
PubMed: 37046037
DOI: 10.1007/s10072-023-06790-0 -
Epilepsia Aug 2022This study was undertaken to review the reported performance of noninvasive wearable devices in detecting epileptic seizures and psychogenic nonepileptic seizures (PNES). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study was undertaken to review the reported performance of noninvasive wearable devices in detecting epileptic seizures and psychogenic nonepileptic seizures (PNES).
METHODS
We conducted a systematic review and meta-analysis of studies reported up to November 15, 2021. We included studies that used video-electroencephalographic (EEG) monitoring as the gold standard to determine the sensitivity and false alarm rate (FAR) of noninvasive wearables for automated seizure detection.
RESULTS
Twenty-eight studies met the criteria for the systematic review, of which 23 were eligible for meta-analysis. These studies (1269 patients in total, median recording time = 52.9 h per patient) investigated devices for tonic-clonic seizures using wrist-worn and/or ankle-worn devices to measure three-dimensional accelerometry (15 studies), and/or wearable surface devices to measure electromyography (eight studies). The mean sensitivity for detecting tonic-clonic seizures was .91 (95% confidence interval [CI] = .85-.96, I = 83.8%); sensitivity was similar between the wrist-worn (.93) and surface devices (.90). The overall FAR was 2.1/24 h (95% CI = 1.7-2.6, I = 99.7%); FAR was higher in wrist-worn (2.5/24 h) than in wearable surface devices (.96/24 h). Three of the 23 studies also detected PNES; the mean sensitivity and FAR from these studies were 62.9% and .79/24 h, respectively. Four studies detected both focal and tonic-clonic seizures, and one study detected focal seizures only; the sensitivities ranged from 31.1% to 93.1% in these studies.
SIGNIFICANCE
Reported noninvasive wearable devices had high sensitivity but relatively high FARs in detecting tonic-clonic seizures during limited recording time in a video-EEG setting. Future studies should focus on reducing FAR, detection of other seizure types and PNES, and longer recording in the community.
Topics: Accelerometry; Electroencephalography; Epilepsy; Humans; Psychogenic Nonepileptic Seizures; Seizures; Wearable Electronic Devices
PubMed: 35545836
DOI: 10.1111/epi.17297 -
Epilepsia May 2021Absence seizures (AS), presenting as short losses of consciousness with staring spells, are a common manifestation of childhood epilepsy that is associated with... (Meta-Analysis)
Meta-Analysis
Absence seizures (AS), presenting as short losses of consciousness with staring spells, are a common manifestation of childhood epilepsy that is associated with behavioral, emotional, and social impairments. It has also been suggested that patients with AS are more likely to suffer from mood disorders such as depression and anxiety. This systematic review and meta-analysis synthesizes human and animal models that investigated mood disorders and AS. Of the 1019 scientific publications identified, 35 articles met the inclusion criteria for this review. We found that patients with AS had greater odds of developing depression and anxiety when compared to controls (odds ratio = 4.93, 95% confidence interval = 2.91-8.35, p < .01). The included studies further suggest a strong correlation between AS and depression and anxiety in the form of a bidirectional relationship. The current literature emphasizes that these conditions likely share underlying mechanisms, such as genetic predisposition, neurophysiology, and anatomical pathways. Further research will clarify this relationship and ensure more effective treatment for AS and mood disorders.
Topics: Animals; Anxiety; Depression; Epilepsy, Absence; Humans; Seizures
PubMed: 33751566
DOI: 10.1111/epi.16862 -
The Cochrane Database of Systematic... Oct 2019Epilepsy affects approximately 1% of the population, with up to 30% of patients continuing to have seizures, despite antiepileptic drug treatment. Clobazam is a... (Review)
Review
BACKGROUND
Epilepsy affects approximately 1% of the population, with up to 30% of patients continuing to have seizures, despite antiepileptic drug treatment. Clobazam is a 1,5-benzodiazepine and is commonly used as an add-on treatment for drug-resistant epilepsy. This review is an updated version of the original Cochrane Review, first published in 2008, and examines the most current literature regarding clobazam as an add-on for drug-resistant epilepsy.
OBJECTIVES
To assess the efficacy, effectiveness and tolerability of clobazam as an add-on therapy for drug-resistant generalised-onset and focal-onset seizures, with or without secondary generalisation, in adults and children.
SEARCH METHODS
For the latest update, we searched the following databases on 9 October 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) 1946 to 8 October, 2018, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). For some previous updates we also searched SCOPUS, DARE, and BIOSIS Previews, but these are no longer needed. (SCOPUS was searched as a substitute for EMBASE, but randomised and quasi-randomised controlled trials in EMBASE are now included in CENTRAL; DARE ceased operation at the end of March 2015; BIOSIS Previews yielded no relevant items that were not found in the other databases).
SELECTION CRITERIA
Randomised trials of add-on clobazam, with adequate methods of allocation concealment, recruiting patients with drug-resistant focal or generalised-onset seizures, with a minimum treatment period of eight weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: 50% or greater reduction in seizures, seizure freedom, treatment withdrawal and adverse events.
MAIN RESULTS
Four double-blind, placebo-controlled, cross-over studies, representing 197 participants, were included in the review. All four studies were assessed as having unclear risk of bias due to the unavailability of methodological details. The studies demonstrated significant methodological heterogeneity and differences in outcome measures were noted. Consequently, it was not possible to summarise the data in a meta-analysis. Instead, findings were summarised in a narrative data synthesis, Only two of the studies reported 50% or greater seizure reduction. They respectively reported that 57.7% and 52.4% of participants receiving add-on clobazam experienced a 50% or greater reduction in seizure frequency, although publication bias needs to be considered (2 RCTs, n = 47, very low-quality evidence). Seizure freedom was reported by three of the included studies. Collectively, 27 out of 175 patients were seizure-free during treatment with clobazam (3 RCTs, n = 175, very low-quality evidence). Two studies specifically stated that seizure freedom was not observed in any of the participants receiving add-on placebo. Treatment withdrawal was reported by all four studies. There was a slightly higher incidence of treatment withdrawal associated with receiving clobazam, although the overall incidence was still fairly low (4 RCTs, n = 197, very low-quality evidence). Adverse events were only described in two of the studies, reportedly 36% and 85% of participants experienced one or more adverse events whilst receiving clobazam. The most commonly reported adverse event was drowsiness.
AUTHORS' CONCLUSIONS
Clobazam as an add-on treatment may reduce seizure frequency and may be most effective in focal-onset seizures. It is important to recognise that this finding has been derived from very low-quality evidence and from studies judged to have an unclear risk of bias. It remains unclear which population demographic will best benefit from clobazam and over what time-frame. A large-scale, randomised controlled trial, conducted over a greater period of time, incorporating subgroups with differing seizure types, is required to effectively inform clinical practice.
PubMed: 31638272
DOI: 10.1002/14651858.CD004154.pub5 -
Frontiers in Neurology 2022Identifying the predictors for seizure outcome in autoimmune encephalitis (AE) and investigating how to prevent persistent seizures would have major clinical benefits...
BACKGROUND
Identifying the predictors for seizure outcome in autoimmune encephalitis (AE) and investigating how to prevent persistent seizures would have major clinical benefits effectively. Thus, we aimed to perform a systematic review and meta-analysis to examine seizure outcome-related factors in AE patients.
METHODS
PubMed and EMBASE were systematically searched from inception to 10 June 2022 for studies investigating seizure outcome-related factors in AE. The pooled effect estimates, including standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs), were calculated to estimate the effect of each included factor on the seizure outcome.
RESULTS
A total of 10 studies were included in the meta-analysis. Our pooled results of this meta-analysis showed that five factors were found to increase the risk of persistent seizures in AE patients, including onset with seizures (OR = 2.106, 95% CI = 1.262-3.514, = 0.004), status epilepticus (OR = 3.017, 95% CI = 1.995-4.563, < 0.001), EEG abnormalities (OR = 1.581, 95% CI = 1.016-2.46, = 0.042), MRI abnormalities (OR = 1.554, 95% CI = 1.044-2.283, = 0.03), and longer time from clinical onset to immunotherapy (SMD = 1.887, 95% CI = 0.598-3.156, = 0.004).
CONCLUSION
Our meta-analysis indicated that onset with seizures, status epilepticus, EEG abnormalities, MRI abnormalities, and longer time from clinical onset to immunotherapy were risk factors for persistent seizures in AE patients.
PubMed: 36408506
DOI: 10.3389/fneur.2022.991043 -
Seizure Nov 2022Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures.
METHODS
This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs.
RESULTS
From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I 15% and RR 2.79, 95% CI 1.58 to 4.93, I 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes.
CONCLUSION
This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.
Topics: Humans; Anticonvulsants; Treatment Outcome; Pyridones; Seizures; Epilepsy; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36206645
DOI: 10.1016/j.seizure.2022.09.020 -
The Cochrane Database of Systematic... Sep 2022This is an updated version of the Cochrane Review first published in 2014 and last updated in 2020. For nearly 30% of people with epilepsy, current treatments do not... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review first published in 2014 and last updated in 2020. For nearly 30% of people with epilepsy, current treatments do not control seizures. Stiripentol is an antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 as an adjunctive therapy with valproate and clobazam for the treatment of Dravet syndrome.
OBJECTIVES
To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with drug-resistant focal epilepsy who are taking AEDs.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE on 28 March 2022. We contacted the manufacturer of stiripentol and epilepsy experts to identify published, unpublished and ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of add-on stiripentol in people with drug-resistant focal epilepsy.
DATA COLLECTION AND ANALYSIS
Review authors independently selected trials for inclusion and extracted data. We investigated outcomes including 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life.
MAIN RESULTS
On the basis of our selection criteria, we included no new studies in the present review update. We included only one study from the original review (32 children with focal epilepsy). This study adopted a responder-enriched design and found no clear evidence of a reduction of 50% or more in seizure frequency (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82; low-certainty evidence) and no clear evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43; low-certainty evidence) when comparing add-on stiripentol with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47; low-certainty evidence). When we considered specific adverse effects, CIs were very wide and showed the possibility of substantial increases and small reductions in risks of neurological adverse effects (RR 2.65, 95% CI 0.88 to 8.01; low-certainty evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47; low-certainty evidence), which was high in both groups (53.3% in placebo group and 35.3% in stiripentol group; low-certainty evidence). The external validity of this study was limited because only responders to stiripentol (i.e. participants experiencing a decrease in seizure frequency of 50% or greater during an open prerandomisation phase compared with baseline) were included in the randomised, add-on, placebo-controlled, double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole may occur more often with add-on stiripentol than with add-on placebo.
AUTHORS' CONCLUSIONS
We have found no new studies since the last version of this review was published. Hence, we have made no changes to the conclusions as presented in previous versions. We can draw no conclusions to support the use of stiripentol as add-on treatment for drug-resistant focal epilepsy. Additional large, randomised, well-conducted trials are needed.
Topics: Anticonvulsants; Child; Dioxolanes; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Quality of Life; Randomized Controlled Trials as Topic; Seizures
PubMed: 36066395
DOI: 10.1002/14651858.CD009887.pub6 -
International Journal of Preventive... 2021Seizure and epilepsy are among the initial symptoms of multiple sclerosis (MS), yet different prevalence rates are reported for them in the previous studies. The goal of... (Review)
Review
BACKGROUND
Seizure and epilepsy are among the initial symptoms of multiple sclerosis (MS), yet different prevalence rates are reported for them in the previous studies. The goal of this systematic review is to estimate the pooled prevalence of seizure and epilepsy in patients with MS.
METHODS
We searched PubMed, Scopus, EMBASE, Web of Science, google scholar, and gray literature including references from identified studies and conference abstracts published up to October 2019. The search strategy included the MeSH terms and text words as ((Epilepsies OR Seizure Disorder OR Seizure Disorders OR Awakening Epilepsy OR Epilepsy, Awakening OR Epilepsy, Cryptogenic OR Cryptogenic Epilepsies OR Cryptogenic Epilepsy OR Epilepsies, Cryptogenic OR epilepsy OR seizure) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating).
RESULTS
The literature review resulted in 4860 articles; 2593 articles remained after eliminating the duplicates. For the final analysis, 39 articles were included, 9 of which were conference abstracts. The pooled prevalence of seizure in MS cases was 2%, 95% confidence interval (CI)(1%-3%) (I = 91.8%, < 0.001). The pooled prevalence of epilepsy in MS cases was 3%, 95% CI (2%-4%) (I2 = 92.9%, < 0.001). The pooled prevalence of epilepsy in Asia, Europe, and America was 6%, 3%, and 3%, respectively. The level of heterogeneity decreased after subgroup analysis in Asian and American subgroups. Meta-regression analysis showed continent is not a source of heterogeneity (coefficient = -0.007, = 0.6).
CONCLUSIONS
The result of this systematic review shows that the pooled prevalence of seizure and epilepsy among MS patients is 2% and 3%, respectively.
PubMed: 34084311
DOI: 10.4103/ijpvm.IJPVM_75_20 -
The Cochrane Database of Systematic... Jan 2022The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs... (Review)
Review
BACKGROUND
The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term adverse effects. Hence, when a person with epilepsy is in remission, it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review examines the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on seizure recurrence. This is an updated version of the Cochrane Review previously published in 2020.
OBJECTIVES
To quantify risk of seizure recurrence after rapid (tapering period of three months or less) or slow (tapering period of more than three months) discontinuation of antiepileptic drugs in adults and children with epilepsy who are in remission, and to assess which variables modify the risk of seizure recurrence.
SEARCH METHODS
For the latest update, on 8 November 2021, we searched: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid), and SCOPUS. There were no language restrictions. CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), CENTRAL, and the Specialized Registers of Cochrane Review Groups including Epilepsy.
SELECTION CRITERIA
Randomized controlled trials that evaluated withdrawal of AEDs in a rapid or slow tapering after varying periods of seizure control in people with epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure freedom after one, two, or five years of AED withdrawal; time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure, such as injuries, fractures, and aspiration pneumonia; and quality of life (assessed by validated scale).
MAIN RESULTS
There are two included studies in this review. One study randomized 57 children with epilepsy with seizure freedom for at least two years to taper down the AED over one or six months. The study was not blinded and there were no details of randomization. Over the period of 54 months of follow-up, 20/30 participants in the one-month group remained seizure-free compared to 15/27 participants in the six-month group (no evidence of a difference). There was no information on time of seizure recurrence for each group to allow a comparison. The other study involved 149 children. There was a non-significant trend towards a lower risk of seizure recurrence after one year of AED withdrawal in participants allocated to slow tapering (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 1.01; P = 0.06; very low-certainty evidence). At the end of two years, 30 participants were seizure free in the rapid-tapering group and 29 participants in the slow-tapering group (RR 0.87, 95% CI 0.58 to 1.29; P = 0.48; very low-certainty evidence). At the end of five years, 10 participants were seizure free in the rapid-tapering group and six participants in the slow-tapering group (RR 1.40, 95% CI 0.54 to 3.65; P = 0.49; very low-certainty evidence). There were no data for the other outcomes. Due to the methodological heterogeneity and the difference in the duration of tapering, we did not perform a quantitative synthesis of these studies. Currently, one Italian trial is ongoing that is investigating if a slow or a rapid withdrawal schedule of AEDs influences return of seizures (relapse) in adults with focal or generalized epilepsy who have been seizure free for at least two years (no preliminary results available).
AUTHORS' CONCLUSIONS
In view of methodological deficiencies, and small sample size of the two included studies, we cannot draw any reliable conclusions regarding the optimal rate of tapering of AEDs. Using GRADE, we assessed the certainty of the evidence as very low for outcomes for which data were available. We judged both studies to be at an overall high risk of bias. Further studies are needed in adults and children to investigate the optimal rate of withdrawal of AEDs and to study the effects of variables such as seizure types, aetiology, intellectual disability, electroencephalography abnormalities, presence of neurological deficits, and other comorbidities on the rate of tapering.
Topics: Adult; Anticonvulsants; Child; Epilepsy; Epilepsy, Generalized; Humans; Quality of Life; Seizures
PubMed: 35005782
DOI: 10.1002/14651858.CD005003.pub4