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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 We contacted the manufacturer of stiripentol and epilepsy experts to identify published, unpublished and ongoing trials.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 -
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 -
Maedica Dec 2023ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic...
ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic acidosis. A systematic review was conducted with the aim to evaluate the effect of STAN method compared with isolated CTG on perinatal and neonatal outcomes. A search of electronic databases (PubMed, Cochrane, Scopus) was conducted to identify randomized controlled trials (RCTs) in English language. Outcomes considered operative deliveries, fetal blood sampling (FBS), metabolic acidosis, perinatal and neonatal death, neonatal seizures, neonatal encephalopathy, transfer to the neonatal intensive care unit (NICU) and Apgar score. Seven RCTs were included in the present review. The first two RCTs showed that the combination of STAN and CTG was a better option than using CTG alone, because there was a documented reduction in the rate of operative deliveries due to fetal distress and metabolic acidosis. The following studies showed no statistically significant changes with the combination of methods, except from a reduction in FBS. The findings from the RCTs were inconclusive. Most studies did not demonstrate a superiority of the combination regarding operative deliveries and neonatal outcomes but there were many methodological differences between the trials.
PubMed: 38348066
DOI: 10.26574/maedica.2023.18.4.684 -
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 -
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 -
Frontiers in Human Neuroscience 2023The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no... (Review)
Review
BACKGROUND
The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no uniform treatment guidelines.
OBJECTIVE
To summarize the clinical characteristics of patients with anti-NMDAR encephalitis and to analyze the factors affecting the disease prognosis.
METHODS
A systematic analysis of medical records was conducted, and PubMed, Embase, and Cochrane Library were searched from January 1, 2011, to December 31, 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
This study included 472 case reports. Most patients had prodromal symptoms of about 2 weeks, including psychiatric symptoms (53.2%), flu-like symptoms (51.5%), and seizures (23.9%), among others. Poor prognoses were associated with patients who had autonomic instability ( = 0.010), central hypoventilation ( = 0.014), and ICU support ( = 0.002). Patients with a higher age of onset were more likely to develop central hypoventilation (OR 1.024, CI 1.006-1.042, = 0.009), cognitive impairment (OR 1.023, CI 1.009-1.037, = 0.001), and memory impairment (OR 1.034, CI 1.017-1.050, < 0.001), whereas patients with a lower age were more likely to have seizures (OR 0.979, CI 0.965-0.993, = 0.003). In this study, 97.0% of patients received immunotherapy, with the most commonly used treatment regimen being intravenous methylprednisolone (IVGC) and intravenous immunoglobulin (IVIG). When compared with other treatment regimens, the IVGC+IVIG regimen ( < 0.001) resulted in better prognoses.
CONCLUSION
When encountering patients with fever, headache, and initial psychiatric symptoms of unknown etiology, clinicians should test their CSF for antibodies to distinguish autoimmune encephalitis. Patients with autonomic instability, central hypoventilation, and ICU support had poorer prognoses. Clinicians should be aware that older patients are more likely to develop central hypoventilation, cognitive impairment, and memory impairment, while younger patients are more likely to develop seizures. The IVGC+IVIG treatment regimen has better prognoses than others. This study includes case reports, which have obvious selection bias, and there are no unified standards to measure the severity of the disease. Therefore, in the future, larger samples and randomized controlled trials are needed to evaluate the efficacy of different treatment regimens.
PubMed: 38053649
DOI: 10.3389/fnhum.2023.1261638 -
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