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Epilepsy & Behavior : E&B May 2023Different neurostimulation modalities are available to treat drug-resistant focal epilepsy when surgery is not an option including vagus nerve stimulation (VNS),... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Different neurostimulation modalities are available to treat drug-resistant focal epilepsy when surgery is not an option including vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). Head-to-head comparisons of efficacy do not exist between them nor are likely to be available in the future. We performed a meta-analysis on VNS, RNS, and DBS outcomes to compare seizure reduction efficacy for focal epilepsy.
METHODS
We systematically reviewed the literature for reported seizure outcomes following implantation with VNS, RNS, and DBS in focal-onset seizures and performed a meta-analysis. Prospective or retrospective clinical studies were included.
RESULTS
Sufficient data were available at years one (n = 642, two (n = 480), and three (n = 385) for comparing the three modalities with each other. Seizure reduction for the devices at years one, two, and three respectively were: RNS: 66.3%, 56.0%, 68.4%; DBS- 58.4%, 57.5%, 63.8%; VNS 32.9%, 44.4%, 53.5%. Seizure reduction at year one was greater for RNS (p < 0.01) and DBS (p < 0.01) compared to VNS.
CONCLUSIONS
Our findings indicate the seizure reduction efficacy of RNS is similar to DBS, and both had greater seizure reductions compared to VNS in the first-year post-implantation, with the differences diminishing with longer-term follow-up.
SIGNIFICANCE
The results help guide neuromodulation treatment in eligible patients with drug-resistant focal epilepsy.
Topics: Humans; Retrospective Studies; Prospective Studies; Deep Brain Stimulation; Epilepsies, Partial; Drug Resistant Epilepsy; Seizures; Vagus Nerve Stimulation; Treatment Outcome
PubMed: 36972642
DOI: 10.1016/j.yebeh.2023.109182 -
The Cochrane Database of Systematic... Oct 2023This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the... (Review)
Review
BACKGROUND
This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the population. Pharmacological treatment remains the first choice to control epilepsy. However, up to 30% of people do not respond to drug treatment, and therefore do not achieve seizure remission. Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy.
OBJECTIVES
To assess the efficacy and tolerability of immunomodulatory interventions on seizures, adverse effect profile, cognition, and quality of life, compared to placebo controls, when used as additional therapy for focal epilepsy in children and adults.
SEARCH METHODS
For the latest update, we searched the following databases on 11 November 2021: Cochrane Register of Studies (CRS Web) and Medline (Ovid) 1946 to 10 November 2021. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. We placed no language restrictions. We reviewed the bibliographies of retrieved studies to search for additional reports of relevant studies.
SELECTION CRITERIA
Randomised placebo-controlled trials of add-on immunomodulatory drug interventions, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. Eligible participants were children (aged over 2 years) and adults with focal epilepsy.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration. We assessed the following outcomes. 1. 50% or greater reduction in seizure frequency. 2. Seizure freedom. 3. Treatment withdrawal for any reason. 4. Quality of life. 5.
ADVERSE EFFECTS
We used an intention-to-treat (ITT) population for all primary analyses, and we presented results as risk ratios (RRs) with 95% confidence intervals (95% Cl).
MAIN RESULTS
We included three randomised, double-blind, placebo-controlled trials on a total of 172 participants. All trials included children and adults over two years of age with focal epilepsy. Treatment phases lasted six weeks and follow-up from six weeks to six months. One of the three included trials described an adequate method of concealment of randomisation, whilst the other two trials were rated as having an unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in all three trials. All analyses were by ITT. One trial was sponsored by the manufacturer of an immunomodulatory agent and therefore was at high risk of funding bias. Immunomodulatory interventions were significantly more effective than placebo in reducing seizure frequency (risk ratio (RR) 2.30, 95% confidence interval (CI) 1.15 to 4.60; 3 studies, 172 participants; moderate-certainty evidence). For treatment withdrawal, there was insufficient evidence to conclude that people were more likely to discontinue immunomodulatory intervention than placebo (RR 1.04, 95% CI 0.28 to 3.80; 3 studies, 172 participants; low-certainty evidence). The RR for adverse effects was 1.16 (95% CI 0.84 to 1.59; 1 study, 66 participants; low-certainty evidence). Certain adverse effects such as dizziness, headache, fatigue, and gastrointestinal disorders were more often associated with immunomodulatory interventions. There were little to no data on cognitive effects and quality of life. No important heterogeneity between studies was found for any of the outcomes. We judged the overall certainty of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals.
AUTHORS' CONCLUSIONS
Immunomodulatory interventions as add-on treatment for children and adults with focal epilepsy appear to be effective in reducing seizure frequency. It is not possible to draw any conclusions about the tolerability of these agents in children and adults with epilepsy. Further randomised controlled trials are needed.
Topics: Adult; Child; Humans; Aged; Anticonvulsants; Quality of Life; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Seizures; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic
PubMed: 37842826
DOI: 10.1002/14651858.CD009945.pub3 -
The Cochrane Database of Systematic... Oct 2023Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term... (Review)
Review
BACKGROUND
Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.
OBJECTIVES
1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials) Treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months. We report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons.
AUTHORS' CONCLUSIONS
Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.
Topics: Infant; Child; Infant, Newborn; Adult; Humans; Adolescent; Phenytoin; Levetiracetam; Epilepsy; Phenobarbital; Seizures
PubMed: 37873971
DOI: 10.1002/14651858.CD014967.pub2 -
Journal of the Neurological Sciences Sep 2021Epilepsy can be associated with significant morbidity and mortality. Seizure detection devices could be invaluable tools for both people with epilepsy, their caregivers,... (Review)
Review
IMPORTANCE
Epilepsy can be associated with significant morbidity and mortality. Seizure detection devices could be invaluable tools for both people with epilepsy, their caregivers, and clinicians as they could alert caretakers about seizures, reduce the risk of sudden unexpected death in epilepsy, and provide objective and more reliable seizure tracking to guide treatment decisions or monitor outcomes in clinical trials.
OBJECTIVE
To synthesize the characteristics of commercial seizure detection tools/devices currently available.
METHODS
We performed a systematic search utilizing a diverse set of resources to identify commercially available seizure detection products for consumer use. Performance data was obtained through a systematic review on commercially available products.
OBSERVATIONS
We identified 23 products marketed for seizure detection/alerting. Devices utilize a variety of mechanisms to detect seizures, including movement detectors, autonomic change detectors, electroencephalogram (EEG) based detectors, and other mechanisms (audio). The optimal device for a person with epilepsy depends on a variety of factors including the main purpose of the device, their age, seizure type and personal preferences. Only 8 devices have published peer-reviewed performance data and the majority for tonic-clonic seizures. An informed conversation between the clinician and the patient can help guide if a seizure detection device is appropriate.
CONCLUSIONS AND RELEVANCE
Seizure detection devices have a potential to reduce morbidity and mortality for certain people with epilepsy. Clinicians should be familiar with the characteristics of commercially available devices to best counsel their patients on whether a seizure detection device may be beneficial and what the optimal devices may be.
Topics: Autonomic Nervous System; Communication; Electroencephalography; Humans; Movement; Seizures
PubMed: 34419933
DOI: 10.1016/j.jns.2021.117611 -
The Cochrane Database of Systematic... Jul 2022This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator.
OBJECTIVES
To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform.
SELECTION CRITERIA
We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood
MAIN RESULTS
We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes.
AUTHORS' CONCLUSIONS
VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.
Topics: Adult; Anticonvulsants; Child; Cough; Drug Resistant Epilepsy; Drug Therapy, Combination; Dyspnea; Hoarseness; Humans; Pain; Paresthesia; Seizures; Vagus Nerve Stimulation
PubMed: 35833911
DOI: 10.1002/14651858.CD002896.pub3 -
Journal of Medical Virology Sep 2023Seizure aggravation following coronavirus disease 2019 (COVID-19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in... (Meta-Analysis)
Meta-Analysis Review
Seizure aggravation following coronavirus disease 2019 (COVID-19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in lower immunization rates. We systematically reviewed seizure-activity-related events in PwE following COVID-19 vaccination. We systematically searched PubMed, Web of Science, Scopus, and Cochrane Library, until January 31, 2023, and included articles reporting seizure activity-related events in PwE receiving COVID-19 vaccination. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. The protocol was registered with PROSPERO (CRD42022312475). Outcomes included pooled incidence proportions of (a) increased seizure frequency, (b) status epilepticus (SE), and (c) change in seizure type. Of the 2207 studies, 16 entered the meta-analysis. The pooled incidence proportion of increased seizure frequency (16 studies-3245 PwE) was 5% (95% CI: 3%-7%, I = 52%). Regarding increased seizure frequency, no significant difference was observed between mRNA and viral vector (OR: 1.11, 95% CI: 0.49-2.52, I = 0%), and between mRNA and inactivated virus (OR: 1.60, 95% CI: 0.27-9.37; I = 0%). The pooled incidence proportion of SE (15 studies-2387 PwE) was 0.08% (95% CI: 0.02%-0.33%, I = 0%). Ultimately, the pooled incidence proportion of change in seizure type (7 studies-1172 PwE) was 1% (95% CI: 1%-2%, I = 0%). The meta-analysis revealed post-COVID-19-vaccination increased seizure frequency in 5% of PwE, with no difference between mRNA and viral vector or inactivated virus vaccines. Furthermore, we found 0.08% and 1% incidence proportions for postvaccination SE and change in seizure type, respectively. While noteworthy, these values are far less than reports for COVID-19 infection, emphasizing vaccination importance in preventing COVID-19 consequences in PwE.
Topics: Humans; COVID-19 Vaccines; COVID-19; Seizures; Epilepsy; Status Epilepticus; RNA, Messenger
PubMed: 37732629
DOI: 10.1002/jmv.29118 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses. Catamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses. Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group. The results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life. We judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out. Our review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Menstruation; Middle Aged; Randomized Controlled Trials as Topic; Seizures; Young Adult
PubMed: 34528245
DOI: 10.1002/14651858.CD013225.pub3 -
The Journal of International Medical... Nov 2023Due to variability in reports, the aim of this meta-analysis was to evaluate the incidence and risk factors of post-stroke early seizures (ES) and post-stroke epilepsy... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Due to variability in reports, the aim of this meta-analysis was to evaluate the incidence and risk factors of post-stroke early seizures (ES) and post-stroke epilepsy (PSE).
METHODS
The MEDLINE, EMBASE and Web of Science databases were searched for post-stroke ES/PSE articles published on any date up to November 2020. Post-stroke ES included seizures occurring within 7 days of stroke, and PSE included at least one unprovoked seizure. Using random effects models, the incidence and risk factors of post-stroke ES and PSE were evaluated. The study was retrospectively registered with INPLASY (INPLASY2023100008).
RESULTS
Of 128 included studies in total, the incidence of post-stroke ES was 0.07 (95% confidence interval [CI] 0.05, 0.10) and PSE was 0.10 (95% CI 0.08, 0.13). The rates were higher in children than adults. Risk factors for post-stroke ES included hemorrhagic stroke (odds ratio [OR] 2.14, 95% CI 1.44, 3.18), severe strokes (OR 2.68, 95% CI 1.73, 4.14), cortical involvement (OR 3.09, 95% CI 2.11, 4.51) and hemorrhagic transformation (OR 2.70, 95% CI 1.58, 4.60). Risk factors for PSE included severe strokes (OR 4.92, 95% CI 3.43, 7.06), cortical involvement (OR 3.20, 95% CI 2.13, 4.81), anterior circulation infarcts (OR 3.28, 95% CI 1.34, 8.03), hemorrhagic transformation (OR 2.81, 95% CI 1.25, 6.30) and post-stroke ES (OR 7.24, 95% CI 3.73, 14.06).
CONCLUSION
Understanding the risk factors of post-stroke ES/PSE may identify high-risk individuals who might benefit from prophylactic treatment.
Topics: Adult; Child; Humans; Incidence; Seizures; Stroke; Epilepsy; Risk Factors
PubMed: 38008901
DOI: 10.1177/03000605231213231 -
Epilepsy & Behavior : E&B Sep 2023Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence and predictive risk factors for drug-resistant IGE.
METHODS
We systematically searched three databases (PubMed, Embase, and Cochrane Library) in November 2022 and included 12 eligible studies which reported long-term outcomes (mean = 14.05) after antiseizure medications (ASMs) from 2001 to 2020. We defined drug resistance as the persistence of any seizure despite ASMs treatment (whether as monotherapies or in combination) given the criteria of drug resistance varied in original studies. A random-effects model was used to evaluate the prevalence of refractory IGE. Studies reporting potential poor prognostic factors were included for subsequent subgroup meta-analysis.
RESULTS
The pooled prevalence of drug resistance in IGE cohorts was 27% (95% CI: 0.19-0.36). Subgroup analysis of the risk factors revealed that the psychiatric comorbidities (odds ratio (OR): 4.87, 95% confidence interval (CI): 2.97-7.98), combined three seizure types (absences, myoclonic jerks, and generalized tonic-clonic seizures) (OR: 5.37, 95% CI: 3.16-9.13), the presence of absence seizure (OR: 4.38, 95% CI: 2.64-7.28), generalized polyspike trains (GPT) (OR: 4.83, 95% CI: 2.42-9.64), sex/catamenial epilepsy (OR: 3.25, 95% CI: 1.97-5.37), and status epilepticus (OR: 5.94, 95% CI: 2.23-15.85) increased the risk of poor prognosis. Other factors, including age onset, family history, and side effects of ASMs, were insignificantly associated with a higher incidence of refractory IGE.
CONCLUSION
Drug resistance is a severe complication of IGE. Further standardized research about clinical and electroencephalography factors is warranted.
Topics: Humans; Anticonvulsants; Prevalence; Epilepsy, Generalized; Seizures; Drug Resistant Epilepsy; Risk Factors; Immunoglobulin E
PubMed: 37523796
DOI: 10.1016/j.yebeh.2023.109364 -
Epileptic Disorders : International... Apr 2022Stroke is the commonest cause of epileptic seizures in older adults. Risk factors for post-stroke seizure (PSS) are well known, however, predicting PSS risk is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Stroke is the commonest cause of epileptic seizures in older adults. Risk factors for post-stroke seizure (PSS) are well known, however, predicting PSS risk is clinically challenging. This study aimed to evaluate the predictive accuracy of PSS risk prediction models developed to date.
METHODS
We performed a systematic review and meta-analysis of studies using MEDLINE and EMBASE from database inception to 28 December 2020. The search criteria included all peer-reviewed research articles, in which PSS risk prediction models were developed or validated for ischaemic and/or haemorrhagic stroke. Random-effects meta-analysis was used to generate summary statistics of model performance and receiver operating characteristic curves. Quality appraisal of studies was conducted using PROBAST.
RESULTS
Thirteen original studies involving 182,673 stroke patients (mean age: 38-74.9 years; 29.4-60.9% males), reporting 15 PSS risk prediction models were included. The incidence of early PSS (occurring ≤one week from stroke onset) and late PSS (occurring >one week from stroke onset) was 4.5% and 2.1%, respectively. Cortical involvement, functional deficits, increasing lesion size, early seizures, younger age, and haemorrhage were the commonest predictors across the models. SeLECT demonstrated greatest predictive accuracy (AUC 0.77 [95% CI: 0.71-0.82]) for late PSS following ischaemic stroke, and CAVE for predicting late PSS following haemorrhagic stroke (AUC 0.81 [0.76-0.86]). Fourteen of 15 studies demonstrated a high risk of bias, with lack of model validation and reporting of performance measures on calibration and discrimination being the commonest reasons.
SIGNIFICANCE
Although risk factors for PSS are widely documented, this review identified few multivariate models with low risk of bias, synthetising single variables into an individual prediction of seizure risk. Such models may help personalise clinical management and serve as useful research tools by identifying stroke patients at high risk of developing PSS for recruitment into studies of anti-epileptic drug prophylaxis.
Topics: Adult; Aged; Brain Ischemia; Female; Hemorrhagic Stroke; Humans; Male; Middle Aged; Prognosis; Seizures; Stroke
PubMed: 34874273
DOI: 10.1684/epd.2021.1391