-
Drugs Feb 2022Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) are antiseizure medications (ASMs) approved for adjunctive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) are antiseizure medications (ASMs) approved for adjunctive treatment of focal-onset seizures. So far, no randomised controlled trial directly compared the efficacy and safety of these drugs.
OBJECTIVE
We estimated the comparative efficacy and safety of these ASMs for the treatment of focal-onset seizures in adults with epilepsy using a network meta-analysis (NMA).
METHODS
We systematically searched (June week 4, 2021) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ). There were no date limitations or language restrictions. Randomised, double-blinded, controlled, parallel-group, add-on studies that compared oral BRV, CNB, ESL, LCM, and PER versus any comparator over maintenance periods of at least 12 weeks and included adult patients with focal seizures uncontrolled by concomitant ASMs were identified. The efficacy outcomes were the proportions of patients with ≥ 50% and 100% reduction in baseline seizure frequency during the maintenance period. The tolerability outcomes were the proportions of participants who experienced at least one treatment-emergent adverse event (TEAE) and experienced at least one TEAE leading to discontinuation. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA).
RESULTS
Sixteen trials (BRV: n = 3, CNB: n = 1, ESL: n = 4, LCM: n = 4, PER: n = 4) were included, overall enrolling 4507 patients randomised to add-on active treatments (BRV = 803, CNB = 221, ESL =9 90, LCM = 1104, and PER = 1389) and 2246 to add-on placebo. Cenobamate was associated with a higher rate of ≥ 50% seizure frequency reduction than BRV [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.11-3.66], ESL (OR 1.93, 95% CI 1.07-3.48), LCM (OR 1.86, 95% CI 1.04-3.32), and PER (OR 2.07, 95% CI 1.16-3.70). There was a not statistically significant trend favouring CNB over ESL, LCM and PER for the seizure freedom outcome. Brivaracetam (OR 0.61, 95% CI 0.44-0.86) and LCM (OR 0.60, 95% CI 0.40-0.88) were associated with a lower proportion of participants experiencing TEAEs compared to ESL, and patients treated with PER were associated with a higher risk to experience at least one TEAE (OR 1.42, 95% CI 1.02-1.96) than BRV. According to SUCRA, CNB had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction, and BRV and LCM had the highest probabilities of being the best-tolerated treatments.
CONCLUSIONS
Cenobamate ranked best for efficacy, and BRV and LCM were best tolerated over the other comparators. Although NMAs cannot replace direct comparisons, they may support physicians in clinical decision making.
Topics: Adult; Anticonvulsants; Carbamates; Chlorophenols; Dibenzazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lacosamide; Male; Middle Aged; Network Meta-Analysis; Nitriles; Pyridones; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures; Tetrazoles
PubMed: 35061214
DOI: 10.1007/s40265-021-01661-4 -
Cells Aug 2022Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and... (Review)
Review
BACKGROUND
Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics.
AIM
To perform a systematic review of optical biomarkers to identify changes in cerebral haemodynamics and metabolism during the pre-ictal, ictal, and post-ictal phases of neonatal seizures.
METHOD
A systematic search was performed in eight databases. The search combined the three broad categories: (neonates) AND (NIRS) AND (seizures) using the stepwise approach following PRISMA guidance.
RESULTS
Fifteen papers described the haemodynamic and/or metabolic changes observed with NIRS during neonatal seizures. No randomised controlled trials were identified during the search. Studies reported various changes occurring in the pre-ictal, ictal, and post-ictal phases of seizures.
CONCLUSION
Clear changes in cerebral haemodynamics and metabolism were noted during the pre-ictal, ictal, and post-ictal phases of seizures in neonates. Further studies are necessary to determine whether NIRS-based methods can be used at the cot-side to provide clear pathophysiological data in real-time during neonatal seizures.
Topics: Brain; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Seizures; Spectroscopy, Near-Infrared
PubMed: 36010678
DOI: 10.3390/cells11162602 -
Metabolic Brain Disease Dec 2021Neonatal seizures (NS) occur in the first 28 days of life; they represent an important emergency that requires a rapid diagnostic work-up to start a prompt therapy. The... (Review)
Review
Neonatal seizures (NS) occur in the first 28 days of life; they represent an important emergency that requires a rapid diagnostic work-up to start a prompt therapy. The most common causes of NS include: intraventricular haemorrhage, hypoxic-ischemic encephalopathy, hypoglycemia, electrolyte imbalance, neonatal stroke or central nervous system infection. Nevertheless, an Inborn Error of Metabolism (IEM) should be suspected in case of NS especially if these are resistant to common antiseizure drugs (ASDs) and with metabolic decompensation. Nowadays, Expanded Newborn Screening (ENS) has changed the natural history of some IEMs allowing a rapid diagnosis and a prompt onset of specific therapy; nevertheless, not all IEMs are detected by such screening (e.g. Molybdenum-Cofactor Deficiency, Hypophosphatasia, GLUT1-Deficiency Syndrome) and for this reason neonatologists have to screen for these diseases in the diagnostic work-up of NS. For IEMs, there are not specific semiology of seizures and EEG patterns. Herein, we report a systematic review on those IEMs that lead to NS and epilepsy in the neonatal period, studying only those IEMs not included in the ENS with tandem mass, suggesting clinical, biochemical features, and diagnostic work-up. Remarkably, we have observed a worse neurological outcome in infants undergoing only a treatment with common AED for their seizures, in comparison to those primarily treated with specific anti-convulsant treatment for the underlying metabolic disease (e.g.Ketogenic Diet, B6 vitamin). For this reason, we underline the importance of an early diagnosis in order to promptly intervene with a targeted treatment without waiting for drug resistance to arise.
Topics: Epilepsy; Humans; Hypoxia-Ischemia, Brain; Infant; Infant, Newborn; Metabolism, Inborn Errors; Neonatal Screening; Seizures
PubMed: 34403026
DOI: 10.1007/s11011-021-00798-1 -
BMJ Clinical Evidence Nov 2010Simple febrile seizures are generalised in onset, last <15 minutes, and do not occur more than once in 24 hours. Complex febrile seizures are longer lasting, have focal... (Review)
Review
INTRODUCTION
Simple febrile seizures are generalised in onset, last <15 minutes, and do not occur more than once in 24 hours. Complex febrile seizures are longer lasting, have focal symptoms, and can recur within 24 hours. This review only deals with simple febrile seizures. About 2% to 5% of children in the USA and Western Europe, and 6% to 9% of infants and children in Japan will have experienced at least one febrile seizure by the age of 5 years. Simple febrile seizures may slightly increase the risk of developing epilepsy, but have no known adverse effects on behaviour, scholastic performance, or neurocognition.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments given during episodes of fever in children with one or more previous simple febrile seizures? What are the effects of long-term (daily, for >1 month) anticonvulsant treatment in children with a history of simple febrile seizures? What are the effects of treatments on reducing the risk of subsequent epilepsy in children with a history of simple febrile seizures? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants (intermittent or continuous) and antipyretic treatments (physical antipyretic measures, paracetamol, ibuprofen).
Topics: Anticonvulsants; Epilepsy; Fever; Humans; Infant; Recurrence; Seizures; Seizures, Febrile
PubMed: 21406130
DOI: No ID Found -
Neurologia May 2023No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
Topics: Humans; Meningioma; Phenytoin; Anticonvulsants; Incidence; Meningeal Neoplasms
PubMed: 35781420
DOI: 10.1016/j.nrleng.2022.03.002 -
The Turkish Journal of Pediatrics 2020Zinc has been reported to be low in children with febrile seizure compared to febrile cases without seizures, but results are inconsistent. A meta-analysis was performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Zinc has been reported to be low in children with febrile seizure compared to febrile cases without seizures, but results are inconsistent. A meta-analysis was performed to systematically evaluate the serum level of zinc in febrile children aged between 6-72 months with or without seizures.
MATERIAL AND METHODS
A systematic search of databases was performed from January 2000 to January 2019. Studies comparing the serum level of zinc in febrile children with or without seizure were selected.
RESULTS
The major outcome was serum level of zinc. Random effect model was used to calculate pooled standardized mean differences (SMD) with 95% confidence intervals (CIs). A total of 31 articles were included. Meta-analysis suggested that the serum level of zinc is lower in patients with febrile seizure versus febrile cases without seizure (SMD: -1.2, 95%CI= (-1.47, -0.93). In subgroup and sensitivity analysis no significant change was observed in pooled SMD. In meta-regression analysis sample size as a continuous variable had a significant influence on between-study variance (p= 0.02). According to cumulative analysis the difference of serum level of zinc in febrile children with or without seizure decreased with time.
CONCLUSION
This meta-result indicated a significant association of zinc deficiency with seizure in febrile children. It is suspected that decreased level of zinc may be involved in seizure occurrences and it may play a role in the pathogenesis of febrile seizure.
Topics: Child; Child, Preschool; Fever; Humans; Infant; Malnutrition; Seizures; Seizures, Febrile; Zinc
PubMed: 32558408
DOI: 10.24953/turkjped.2020.03.001 -
The Cochrane Database of Systematic... Feb 2017Cardiotocography (CTG) records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiotocography (CTG) records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of oxygen (hypoxic) to guide additional assessments of fetal wellbeing, or determine if the baby needs to be delivered by caesarean section or instrumental vaginal birth. This is an update of a review previously published in 2013, 2006 and 2001.
OBJECTIVES
To evaluate the effectiveness and safety of continuous cardiotocography when used as a method to monitor fetal wellbeing during labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 November 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials involving a comparison of continuous cardiotocography (with and without fetal blood sampling) with no fetal monitoring, intermittent auscultation intermittent cardiotocography.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility, quality and extracted data from included studies. Data were checked for accuracy.
MAIN RESULTS
We included 13 trials involving over 37,000 women. No new studies were included in this update.One trial (4044 women) compared continuous CTG with intermittent CTG, all other trials compared continuous CTG with intermittent auscultation. No data were found comparing no fetal monitoring with continuous CTG. Overall, methodological quality was mixed. All included studies were at high risk of performance bias, unclear or high risk of detection bias, and unclear risk of reporting bias. Only two trials were assessed at high methodological quality.Compared with intermittent auscultation, continuous cardiotocography showed no significant improvement in overall perinatal death rate (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.59 to 1.23, N = 33,513, 11 trials, low quality evidence), but was associated with halving neonatal seizure rates (RR 0.50, 95% CI 0.31 to 0.80, N = 32,386, 9 trials, moderate quality evidence). There was no difference in cerebral palsy rates (RR 1.75, 95% CI 0.84 to 3.63, N = 13,252, 2 trials, low quality evidence). There was an increase in caesarean sections associated with continuous CTG (RR 1.63, 95% CI 1.29 to 2.07, N = 18,861, 11 trials, low quality evidence). Women were also more likely to have instrumental vaginal births (RR 1.15, 95% CI 1.01 to 1.33, N = 18,615, 10 trials, low quality evidence). There was no difference in the incidence of cord blood acidosis (RR 0.92, 95% CI 0.27 to 3.11, N = 2494, 2 trials, very low quality evidence) or use of any pharmacological analgesia (RR 0.98, 95% CI 0.88 to 1.09, N = 1677, 3 trials, low quality evidence).Compared with intermittent CTG, continuous CTG made no difference to caesarean section rates (RR 1.29, 95% CI 0.84 to 1.97, N = 4044, 1 trial) or instrumental births (RR 1.16, 95% CI 0.92 to 1.46, N = 4044, 1 trial). Less cord blood acidosis was observed in women who had intermittent CTG, however, this result could have been due to chance (RR 1.43, 95% CI 0.95 to 2.14, N = 4044, 1 trial).Data for low risk, high risk, preterm pregnancy and high-quality trials subgroups were consistent with overall results. Access to fetal blood sampling did not appear to influence differences in neonatal seizures or other outcomes.Evidence was assessed using GRADE. Most outcomes were graded as low quality evidence (rates of perinatal death, cerebral palsy, caesarean section, instrumental vaginal births, and any pharmacological analgesia), and downgraded for limitations in design, inconsistency and imprecision of results. The remaining outcomes were downgraded to moderate quality (neonatal seizures) and very low quality (cord blood acidosis) due to similar concerns over limitations in design, inconsistency and imprecision.
AUTHORS' CONCLUSIONS
CTG during labour is associated with reduced rates of neonatal seizures, but no clear differences in cerebral palsy, infant mortality or other standard measures of neonatal wellbeing. However, continuous CTG was associated with an increase in caesarean sections and instrumental vaginal births. The challenge is how best to convey these results to women to enable them to make an informed decision without compromising the normality of labour.The question remains as to whether future randomised trials should measure efficacy (the intrinsic value of continuous CTG in trying to prevent adverse neonatal outcomes under optimal clinical conditions) or effectiveness (the effect of this technique in routine clinical practice).Along with the need for further investigations into long-term effects of operative births for women and babies, much remains to be learned about the causation and possible links between antenatal or intrapartum events, neonatal seizures and long-term neurodevelopmental outcomes, whilst considering changes in clinical practice over the intervening years (one-to-one-support during labour, caesarean section rates). The large number of babies randomised to the trials in this review have now reached adulthood and could potentially provide a unique opportunity to clarify if a reduction in neonatal seizures is something inconsequential that should not greatly influence women's and clinicians' choices, or if seizure reduction leads to long-term benefits for babies. Defining meaningful neurological and behavioural outcomes that could be measured in large cohorts of young adults poses huge challenges. However, it is important to collect data from these women and babies while medical records still exist, where possible describe women's mobility and positions during labour and birth, and clarify if these might impact on outcomes. Research should also address the possible contribution of the supine position to adverse outcomes for babies, and assess whether the use of mobility and positions can further reduce the low incidence of neonatal seizures and improve psychological outcomes for women.
Topics: Cardiotocography; Cesarean Section; Female; Heart Auscultation; Heart Rate, Fetal; Humans; Infant; Infant Mortality; Infant, Newborn; Labor, Obstetric; Pregnancy; Randomized Controlled Trials as Topic; Seizures
PubMed: 28157275
DOI: 10.1002/14651858.CD006066.pub3 -
BMJ Clinical Evidence May 2008Simple febrile seizures are generalised in onset, last less than 15 minutes, and do not occur more than once in 24 hours. Complex seizures are longer lasting, have focal... (Review)
Review
INTRODUCTION
Simple febrile seizures are generalised in onset, last less than 15 minutes, and do not occur more than once in 24 hours. Complex seizures are longer lasting, have focal symptoms, and can recur within 24 hours. This review only deals with simple febrile seizures. About 2-5% of children in the USA and Western Europe, and 6-9% of infants and children in Japan, will have experienced at least one febrile seizure by the age of 5 years. Simple febrile seizures may slightly increase the risk of developing epilepsy, but have no known adverse effects on behaviour, scholastic performance, or neurocognition.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments given during episodes of fever in children with one or more previous simple febrile seizures? What are the effects of long-term (daily, for more than 1 month) anticonvulsant treatment in children with a history of simple febrile seizures? What are the effects of treatments on reducing the risk of subsequent epilepsy in children with a history of simple febrile seizures? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants (intermittent or continuous), and antipyretic treatments (physical antipyretic measures, paracetamol, ibuprofen).
Topics: Anticonvulsants; Epilepsy; Fever; Humans; Infant; Recurrence; Seizures, Febrile
PubMed: 19450310
DOI: No ID Found -
Neurologia Sep 2020No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Review)
Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
PubMed: 32896461
DOI: 10.1016/j.nrl.2020.06.014 -
Brain and Behavior May 2021Suicide is a major public health issue and the majority of those who attempt suicide suffer from mental disorders. Beyond psychopharmacotherapy, seizure therapies and... (Review)
Review
BACKGROUND
Suicide is a major public health issue and the majority of those who attempt suicide suffer from mental disorders. Beyond psychopharmacotherapy, seizure therapies and noninvasive brain stimulation interventions have been used to treat such patients. However, the effect of these nonpharmacological treatments on the suicidal ideation and incidence of suicidality remains unclear. Here, we aimed to provide an update on the effects of seizure therapies and noninvasive brain stimulation on suicidality.
METHODS
We conducted a systematic review of the literature in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Elsevier ScienceDirect, and Wiley Online Library databases using the MeSH terms "Electroconvulsive Therapy", "Magnetic Seizure Stimulation", "repetitive Transcranial Magnetic Stimulation", "transcranial Direct Current Stimulation", "Cranial Electrostimulation" and "suicide". We included studies using seizure therapies and noninvasive brain stimulation as a main intervention that evaluated suicidality, regardless of diagnosis.
RESULTS
Among 1,019 records screened, 26 studies met the inclusion criteria using either electroconvulsive therapy (n = 14), magnetic seizure therapy (n = 2), repetitive transcranial magnetic stimulation (n = 9), or transcranial direct current stimulation (n = 1). We observed that studies reported significant results, suggesting these techniques can be effective on the suicidal dimension of mental health pathologies, but a general statement regarding their efficacy is premature due to limitations.
CONCLUSIONS
Future enquiry is necessary to address methodological limitations and evaluate the long-term efficacy of these methods both alone and in combination with pharmacotherapy and/or psychotherapy.
Topics: Brain; Humans; Seizures; Suicide; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 33838000
DOI: 10.1002/brb3.2144