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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 -
Children (Basel, Switzerland) Mar 2023Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein... (Review)
Review
BACKGROUND
Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects).
PATIENTS AND METHODS
We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected.
RESULTS
497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed.
CONCLUSIONS
Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.
PubMed: 36980111
DOI: 10.3390/children10030553 -
Journal of Medical Toxicology :... Jul 2022Cannabis' effect on seizure activity is an emerging topic that remains without consensus and merits further investigation. We therefore performed a scoping review to... (Review)
Review
INTRODUCTION
Cannabis' effect on seizure activity is an emerging topic that remains without consensus and merits further investigation. We therefore performed a scoping review to identify the available evidence and knowledge gaps within the existing literature on cannabis product exposures as a potential cause of seizures in humans.
METHODS
A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews guidelines. The PubMed and Scopus databases were searched over a 20-year period from the date of the database query (12/21/2020). Inclusion criteria were (1) English language original research articles, (2) inclusion of human subjects, and (3) either investigation of seizures as a part of recreational cannabinoid use OR of exogenous cannabinoids as a cause of seizures.
RESULTS
A total of 3104 unique articles were screened, of which 68 underwent full-text review, and 13 met inclusion/exclusion criteria. Ten of 11 studies evaluating acute cannabis exposures reported a higher seizure incidence than would be expected based on the prevalence of epilepsy in the general and pediatric populations (range 0.7-1.2% and 0.3-0.5% respectively). The remaining two studies demonstrated increased seizure frequency and/or seizure-related hospitalization in recreational cannabis users and those with cannabis use disorder.
CONCLUSIONS
This scoping review demonstrates that a body of literature describing seizures in the setting of cannabis exposure exists, but it has several limitations. Ten identified studies showed a higher than expected incidence of seizures in populations exposed to cannabis products. Based on the Bradford Hill criteria, delta-9 tetrahydrocannabinol (THC) may be the causative xenobiotic for this phenomenon.
Topics: Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Child; Hallucinogens; Humans; Seizures
PubMed: 35352276
DOI: 10.1007/s13181-022-00886-3 -
The Cochrane Database of Systematic... Dec 2019Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological abnormalities, such as low serum immunoglobulin A (IgA) levels, lack of the immunoglobulin G (IgG) subclass and identification of certain types of antibodies. Intravenous immunoglobulin (IVIg) treatment may represent a valuable approach and its efficacy has important implications for epilepsy management. This is an update of a Cochrane review first published in 2011 and last updated in 2017.
OBJECTIVES
To examine the effects of IVIg on the frequency and duration of seizures, quality of life and adverse effects when used as monotherapy or as add-on treatment for people with epilepsy.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) (20 December 2018), MEDLINE (Ovid, 1946 to 20 December 2018), Web of Science (1898 to 20 December 2018), ISRCTN registry (20 December 2018), WHO International Clinical Trials Registry Platform (ICTRP, 20 December 2018), the US National Institutes of Health ClinicalTrials.gov (20 December 2018), and reference lists of articles.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of IVIg as monotherapy or add-on treatment in people with epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the trials for inclusion and extracted data. We contacted study authors for additional information. Outcomes included percentage of people rendered seizure-free, 50% or greater reduction in seizure frequency, adverse effects, treatment withdrawal and quality of life.
MAIN RESULTS
We included one study (61 participants). The included study was a randomised, double-blind, placebo-controlled, multicentre trial which compared the treatment efficacy of IVIg as an add-on with a placebo add-on in patients with drug-resistant epilepsy. Seizure freedom was not reported in the study. There was no significant difference between IVIg and placebo in 50% or greater reduction in seizure frequency (RR 1.89, 95% CI 0.85 to 4.21; one study, 58 participants; low-certainty evidence). The study reported a statistically significant effect for global assessment in favour of IVIg (RR 3.29, 95% CI 1.13 to 9.57; one study, 60 participants; low-certainty evidence). No adverse effects were demonstrated. We found no randomised controlled trials that investigated the effects of IVIg monotherapy for epilepsy. Overall, the included study was rated at low to unclear risk of bias. Using GRADE methodology, the certainty of the evidence was rated as low.
AUTHORS' CONCLUSIONS
We cannot draw any reliable conclusions regarding the efficacy of IVIg as a treatment for epilepsy. Further randomised controlled trials are needed.
Topics: Anticonvulsants; Epilepsy; Humans; Immunoglobulins, Intravenous; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome
PubMed: 31792946
DOI: 10.1002/14651858.CD008557.pub4 -
Seizure Jul 2018Febrile seizures (FSs) are the most common form of childhood seizures. During infection, both pro-inflammatory and anti-inflammatory cytokines are produced. Complex... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Febrile seizures (FSs) are the most common form of childhood seizures. During infection, both pro-inflammatory and anti-inflammatory cytokines are produced. Complex interactions among immune-inflammatory process, cytokine activation, and genetic factors are involved in the pathogenesis of FSs. The association between cytokines and FSs during childhood is inconclusive due to inconsistent results reported in different studies. We performed a systematic review and meta-analysis to determine an association between cytokines and FS in children.
METHODS
We searched PubMed, EMBASE, and Cochrane databases for studies published up to January 2017 using the following key words: ["cytokine" OR "interleukin" OR "tumor necrosis factor alpha" OR "interferon-gamma" OR "single nucleotide polymorphism"] AND ["febrile seizure" OR "febrile convulsion"] AND ["pediatric" OR "infant" OR "child"]. Standardized mead difference (SMD) and 95% confidence intervals (CI) were calculated using standard meta-analysis techniques.
RESULTS
A total of 6 studies enrolling 243 children with FS and 234 controls were included in the meta-analysis. A total of 4 different inflammatory mediators were. The results indicated that CSF IL-1β level and serum IL-6 level were significantly associated with FS (CSF IL-1β: SMD, 1.064; 95% CI, 0.217-1.611; P < 0.01, serum IL-6 SMD, 2.654; 95% CI, 2.332-2.975; P < 0.01).
CONCLUSION
The results of this meta-analysis suggest that CSF IL-1β level and serum IL-6 level are associated with an increased risk of FSs in children. Based on these results, it is expected that a therapeutic agent for specific cytokines could be developed in the future to prevent FS.
Topics: Child, Preschool; Cytokines; Humans; Infant; Seizures, Febrile
PubMed: 29727742
DOI: 10.1016/j.seizure.2018.04.023 -
The Cochrane Database of Systematic... Apr 2017Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic... (Review)
Review
BACKGROUND
Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. This is an updated version of the original Cochrane Review published in Issue 12, 2015.
OBJECTIVES
To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME.
SEARCH METHODS
For the latest update, on 21 February 2017 we searched Cochrane Epilepsy's Specialized Register, CENTRAL, MEDLINE, and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.
MAIN RESULTS
We included three studies with 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low.
AUTHORS' CONCLUSIONS
Since the last version of this review we found no new studies. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Adolescent; Anticonvulsants; Child; Fructose; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Treatment Outcome; Valproic Acid; Young Adult
PubMed: 28434203
DOI: 10.1002/14651858.CD010008.pub3 -
Frontiers in Pediatrics 2023Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of... (Review)
Review
BACKGROUND
Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE.
METHODS
We described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science.
RESULTS
Seven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1-17 months of life.
DISCUSSION
Neonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting.
CONCLUSIONS
Ketamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed.
PubMed: 37334223
DOI: 10.3389/fped.2023.1189478 -
Journal of the American Geriatrics... Jul 2021Coexistent seizures add complexity to the burden of Alzheimer's disease (AD). We aim to estimate the incidence and prevalence of coexistent seizures and AD and summarize...
BACKGROUND/OBJECTIVES
Coexistent seizures add complexity to the burden of Alzheimer's disease (AD). We aim to estimate the incidence and prevalence of coexistent seizures and AD and summarize characteristics.
DESIGN
A systematic review and meta-analysis (PROSPERO protocol registration CRD42020150479).
SETTING
Population-, community-, hospital-, or nursing home-based.
PARTICIPANTS AND MEASUREMENTS
Thirty-nine studies reporting on seizure incidence and prevalence in 21,198 and 380,777 participants with AD, respectively, and AD prevalence in 727,446 participants with seizures. When statistical heterogeneity and inconsistency (assessed by Q statistic and I ) were not shown, rates were synthesized using random effect.
RESULTS
Studies were conducted in Australia, Brazil, Finland, France, Ireland, Italy, Japan, Netherlands, Portugal, Sweden, Taiwan, United Kingdom, and United States. The incidence of seizures among people with clinically diagnosed AD ranged from 4.2 to 31.5 per 1000 person-years. Prevalence of seizures among people with clinically diagnosed AD ranged from 1.5% to 12.7% generally, but it rose to the highest (49.5% of those with early-onset AD) in one study. Meta-analysis reported a combined seizure prevalence rate among people with pathologically verified AD at 16% (95% confidence interval [CI] 14-19). Prevalence of seizure in autosomal dominant AD (ADAD) ranged from 2.8% to 41.7%. Being younger was associated with higher risk of seizure occurrence. Eleven percent of people with adult-onset seizures had AD (95%CI, 7-14).
CONCLUSION
Seizures are common in those with AD, and seizure monitoring may be particularly important for younger adults and those with ADAD.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Comorbidity; Female; Global Health; Humans; Incidence; Male; Prevalence; Seizures
PubMed: 33740274
DOI: 10.1111/jgs.17101 -
Epilepsy & Behavior : E&B May 2021In March 2020, the World Health Organization declared the SARS-CoV-2 infection-related coronavirus Disease (COVID-19) a pandemic. During the first and second waves of... (Review)
Review
PURPOSE
In March 2020, the World Health Organization declared the SARS-CoV-2 infection-related coronavirus Disease (COVID-19) a pandemic. During the first and second waves of the pandemic spread, there have been several reports of COVID-19-associated neurological manifestations, including acute seizures and status epilepticus (SE). In this systematic review, we summarized the available data on clinical features, diagnosis, and therapy of COVID-19-related SE.
METHODS
We performed a systematic search of the literature to identify data on demographics, clinical, neurophysiological, and neuroradiological data of patients with COVID-19-related SE. We used regression models (linear or logistic) with a stepwise forward method to identify features associated with mortality or severity of SE.
RESULTS
Thirty-nine articles were included with a total of 47 cases of SE associated with COVID-19. Age, time between the acute respiratory phase of SARS-CoV-2 infection and SE onset, and hospitalization correlated with a higher SE severity as assessed by quantitative validated scales.
CONCLUSIONS
SE can be a neurological manifestation of SARS-CoV-2 infection. Although a possible association between SE and COVID-19 has been reported, the exact mechanisms are still not fully understood. Systemic inflammatory syndrome due to cytokine release could play a role in COVID-19-related SE.
Topics: COVID-19; Humans; Pandemics; SARS-CoV-2; Seizures; Status Epilepticus
PubMed: 33743344
DOI: 10.1016/j.yebeh.2021.107887 -
Neuro-oncology Jul 2015There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current... (Review)
Review
There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current literature on seizure outcome after radiotherapy and chemotherapy and evaluated the association between seizure outcome and radiological response. Twenty-four studies were available, of which 10 described seizure outcome after radiotherapy and 14 after chemotherapy. All studies demonstrated improvements in seizure outcome after antitumor treatment. Eight studies reporting on imaging response in relation to seizure outcome showed a seizure reduction in a substantial part of patients with stable disease on MRI. Seizure reduction may therefore be the only noticeable effect of antitumor treatment. Our findings demonstrate the clinical relevance of monitoring seizure outcome after radiotherapy and chemotherapy, as well as the potential role of seizure reduction as a complementary marker of tumor response in low-grade glioma patients.
Topics: Brain Neoplasms; Glioma; Humans; Seizures; Treatment Outcome
PubMed: 25813469
DOI: 10.1093/neuonc/nov032