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Journal of Tropical Pediatrics Jan 2021Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Phenobarbitone is used as a first-line drug for neonatal seizures. However, its poor short- and long-term safety profile is concerning. We aim to systematically synthesize the data on the efficacy and safety of phenobarbitone as a first-line agent and compare it against other anti-epileptic drugs (AEDs) in neonates.
METHODS
Using keywords related to the study population (neonatal seizure) and intervention (phenobarbitone), we searched CENTRAL, Embase, PubMed and Web of Science until 15 December 2020. Randomized controlled trials (RCTs) comparing phenobarbitone with any other AED as first-line therapy for seizure control in the neonates were considered eligible. The random-effect meta-analysis was done using RevMan 5.3 software.
RESULTS
We screened through 443 records and identified nine eligible studies (719 participants). Five RCTs comparing phenobarbitone with levetiracetam did not find any difference in seizure control with the first dose [risk ratio (RR) 1.43, 95% CI 0.79-2.57] or adverse effects (RR 4.66; 95% CI 0.33-65.83). Two trials comparing phenobarbitone and phenytoin also did not find any difference in seizure control with the first dose (RR 2.09; 95% CI 0.31-14.03) and other outcomes. Only one RCT compared phenobarbitone and lorazepam and found lorazepam to be more efficacious in seizure control with the first dose (RR 0.71; 95% CI 0.53-0.94). Three trials compared neurodevelopmental outcomes, in which levetiracetam was better in two, whereas one did not find any difference.
CONCLUSION
Phenobarbitone is at least as efficacious and safe as other drugs like phenytoin and levetiracetam. The data over the long-term neurodevelopmental outcome are lacking. The existing evidence is insufficient to recommend other drugs over phenobarbitone.
Topics: Anticonvulsants; Carbamazepine; Humans; Infant, Newborn; Phenobarbital; Phenytoin; Seizures
PubMed: 33598701
DOI: 10.1093/tropej/fmab008 -
World Neurosurgery Dec 2018The seizure outcomes for patients with brain arteriovenous malformations (AVM) who undergo intervention with stereotactic radiosurgery (SRS) are incompletely understood.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The seizure outcomes for patients with brain arteriovenous malformations (AVM) who undergo intervention with stereotactic radiosurgery (SRS) are incompletely understood. We sought to determine, in a systematic review and meta-analysis, the rates of seizure control after SRS for patients with AVM-associated seizures and identify predictive factors.
METHODS
We performed a systematic review of PubMed and MEDLINE databases from January 1987 to January 2018, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting post-SRS outcomes data for ≥5 patients with AVM-associated seizures were included. The seizure outcomes and factors associated with seizure freedom were evaluated using meta-analysis.
RESULTS
A total of 27 studies, comprising 4826 patients, met the inclusion criteria for analysis. One or more seizures occurred in 1456 of 4826 patients (34.7% [26.0-43.9%]), and the mean follow-up was 48 ± 7 months. Seizure control (seizure freedom or seizure improvement) was achieved in 910 of 1312 patients (73.1% [66.9-78.9%]). Seizure freedom was achieved in 597 of 1245 patients (55.7% [44.5-66.6%]). Of 259 patients with seizure freedom, cessation of antiepileptic drugs was achieved in 175 patients (67.3% [46.3-85.1%]). AVM obliteration (odds ratio [OR] 4.61; P < 0.001), shorter seizure duration (OR 6.80; P < 0.001), generalized seizure type (OR 2.27; P = 0.007), and previous AVM hemorrhage (OR 5.10; P < 0.001) were significantly associated with seizure freedom.
CONCLUSIONS
SRS affords seizure control to the majority of patients with AVM-associated seizures, and approximately two thirds of those with seizure freedom are able cease anticonvulsants. Nidal obliteration appears to improve the likelihood of seizure freedom, and thus remains the primary goal of intervention with SRS.
Topics: Anticonvulsants; Humans; Intracranial Arteriovenous Malformations; Odds Ratio; Radiosurgery; Seizures; Treatment Outcome
PubMed: 30149174
DOI: 10.1016/j.wneu.2018.08.121 -
Child's Nervous System : ChNS :... Jul 2021Several variations of functional disconnection surgery have been described for the treatment of lateralized, hemispheric, drug-resistant epilepsy in children. The... (Review)
Review
PURPOSE
Several variations of functional disconnection surgery have been described for the treatment of lateralized, hemispheric, drug-resistant epilepsy in children. The purpose of this study is to investigate the existing literature regarding patient selection, approach, and outcomes after hemispherotomy.
METHODS
A systematic review of the English literature through February 2019 was performed in accordance with the PRISMA statement. The articles were classified by level of evidence and summarized in an evidentiary table. Seizure outcomes, functional outcomes, surgical techniques, complications, and patient selection were critically analyzed.
RESULTS
A total of 173 papers were reviewed, of which 37 met criteria of inclusion and exclusion. Thirteen studies were classified as level III evidence, the remaining reached level IV. Vertical and lateral hemispherotomy achieve similar rates of seizure freedom and functional outcomes, though parasagittal and interhemispheric approaches may have shorter operative times and less blood loss. Etiology, bilateral MRI abnormalities, and nonlateralizing EEG did not predict worse seizure or functional outcomes.
CONCLUSIONS
Both vertical and lateral hemispherotomy approaches result in durable, reproducible benefits to epilepsy severity and functional status in appropriately selected pediatric patients.
Topics: Child; Drug Resistant Epilepsy; Epilepsy; Hemispherectomy; Humans; Seizures; Treatment Outcome
PubMed: 33907902
DOI: 10.1007/s00381-021-05176-x -
Clinical Neurophysiology : Official... Jul 2024Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset....
OBJECTIVE
Increasing evidence suggests that the seizure-onset pattern (SOP) in stereo-electroencephalography (SEEG) is important for localizing the "true" seizure onset. Specifically, SOPs with low-voltage fast activity (LVFA) are associated with seizure-free outcome (Engel I). However, several classifications and various terms corresponding to the same pattern have been reported, challenging its use in clinical practice.
METHOD
Following the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guideline, we performed a systematic review of studies describing SOPs along with accompanying figures depicting the reported SOP in SEEG.
RESULTS
Of 1799 studies, 22 met the selection criteria. Among the various SOPs, we observed that the terminology for low frequency periodic spikes exhibited the most variability, whereas LVFA is the most frequently used term of this pattern. Some SOP terms were inconsistent with standard EEG terminology. Finally, there was a significant but weak association between presence of LVFA and seizure-free outcome.
CONCLUSION
Divergent terms were used to describe the same SOPs and some of these terms showed inconsistencies with the standard EEG terminology. Additionally, our results confirmed the link between patterns with LVFA and seizure-free outcomes. However, this association was not strong.
SIGNIFICANCE
These results underline the need for standardization of SEEG terminology.
Topics: Humans; Electroencephalography; Seizures; Stereotaxic Techniques
PubMed: 38733701
DOI: 10.1016/j.clinph.2024.04.016 -
Seizure Nov 2022Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures.
METHODS
This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs.
RESULTS
From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I 15% and RR 2.79, 95% CI 1.58 to 4.93, I 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes.
CONCLUSION
This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.
Topics: Humans; Anticonvulsants; Treatment Outcome; Pyridones; Seizures; Epilepsy; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36206645
DOI: 10.1016/j.seizure.2022.09.020 -
The Cochrane Database of Systematic... 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 Clinical Neuroscience :... Jan 2020This systematic review and meta-analysis of randomized controlled trials (RCTs) systematically explored the effectiveness and safety of lamotrigine for absence seizures... (Meta-Analysis)
Meta-Analysis
AIMS
This systematic review and meta-analysis of randomized controlled trials (RCTs) systematically explored the effectiveness and safety of lamotrigine for absence seizures in children and adolescents.
METHODS
Keywords searches were conducted in Pubmed Embase Cochrane Central Register of Controlled Trials Wanfang CNKI from inception through March 2019. The RCTs comparing lamotrigine with other drugs and/or placebo for the treatment of absence seizures in children and adolescents were considered in this study. The study was conducted adhering to PRISMA guidelines.
RESULTS
Eight RCTs (n = 787) were included in our study. Among these studies, one study (N = 45 patients) used placebo as a control and seven studies (N = 742 patients) used positive drug controls. For effectiveness, there was significant difference between lamotrigine and valproate [OR = 0.42, 95%CI (0.28-0.63), I = 0%] or ethosuximide [OR = 0.34, 95%CI (0.22-0.53), I = 0%]. For adverse effects (AEs), there was no significant difference between lamotrigine and valproate [OR = 1.17, 95%CI (0.59, 2.32), I = 0%] or ethosuximide [OR = 0.75, 95%CI (0.47, 1.19), I = 92%], and the most common adverse effects of lamotrigine were Rash (7.88%), Fatigue (6.50%) and Headache (6.50%).
CONCLUSIONS
According to current evidence, LTG is less effective than VPA and ESM, however, based on its relative safety, LTG might be reasonably tried as initial therapy in children and adolescents at risk of significant adverse effects from VPA and ESM, and future well-designed studies are needed to confirm our findings.
Topics: Adolescent; Anticonvulsants; Child; Epilepsy, Absence; Female; Humans; Lamotrigine; Male; Seizures
PubMed: 31466903
DOI: 10.1016/j.jocn.2019.08.043 -
International Journal of Clinical... Oct 2017Background The onset of early and/or late seizures in brain injured patients is associated with worse outcome. So far, phenytoin is the most commonly used antiepileptic... (Meta-Analysis)
Meta-Analysis Review
Background The onset of early and/or late seizures in brain injured patients is associated with worse outcome. So far, phenytoin is the most commonly used antiepileptic drug to prevent seizures in this group of patients. Objective In the current metaanalysis, we aimed to compare the efficacy and safety of phenytoin versus levetiracetam for seizure prophylaxis in brain injured patients. Methods A systematic search was conducted in PubMed and Cochrane Library Database by 2 investigators. Four randomized controlled trials (RCTs) were included (295 patients). Data were extracted and the quality of each RCT was assessed. Results Levetiracetam was found to be more effective than phenytoin in seizure prophylaxis (OR = 0.23; CI 95% [0.09-0.56]; Q test p value = 0.18 and I = 38%). A trend toward less serious side effects was also found in patients treated with levetiracetam (OR = 0.27; CI 95% [0.07-1.07]; Q test p value = 0.72 and I = 0%). Conclusion Levetiracetam is more effective and safer than phenytoin for seizure prophylaxis in brain injured patients.
Topics: Anticonvulsants; Brain Injuries; Humans; Levetiracetam; Phenytoin; Piracetam; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Seizures
PubMed: 28780739
DOI: 10.1007/s11096-017-0507-6 -
Epilepsia Sep 2019Invasive monitoring is sometimes necessary to guide resective surgery in epilepsy patients, but the ideal method is unknown. In this systematic review, we assess the...
OBJECTIVE
Invasive monitoring is sometimes necessary to guide resective surgery in epilepsy patients, but the ideal method is unknown. In this systematic review, we assess the association of postresection seizure freedom and adverse events in stereoelectroencephalography (SEEG) and subdural electrodes (SDE).
METHODS
We searched three electronic databases (MEDLINE, Embase, and CENTRAL [Cochrane Central Register of Controlled Trials]) from their inception to January 2018 with the keywords "electroencephalography," "intracranial grid," and "epilepsy." Studies that presented primary quantitative patient data for postresection seizure freedom with at least 1 year of follow-up or complication rates of SEEG- or SDE-monitored patients were included. Two trained investigators independently collected data from eligible studies. Weighted mean differences (WMDs) with 95% confidence interval (CIs) were used as a measure of the association of SEEG or SDE with seizure freedom and with adverse event outcomes.
RESULTS
Of 11 462 screened records, 48 studies met inclusion criteria. These studies reported on 1973 SEEG patients and 2036 SDE patients. Our systematic review revealed SEEG was associated with 61.0% and SDE was associated with 56.4% seizure freedom after resection (WMD = +5.8%, 95% CI = 4.7-6.9%, P = .001). Furthermore, SEEG was associated with 4.8% and SDE was associated with 15.5% morbidity (WMD = -10.6%, 95% CI = -11.6 to -9.6%, P = .001). SEEG was associated with 0.2% mortality and SDE was associated with 0.4% mortality (WMD = -0.2%, 95% CI = -0.3 to -0.1%, P = .001).
SIGNIFICANCE
In this systematic review of SEEG and SDE invasive monitoring techniques, SEEG was associated with fewer surgical resections yet better seizure freedom outcomes in those undergoing resections. SEEG was also associated with lower mortality and morbidity than SDE. Clinical studies directly comparing these modalities are necessary to understand the relative rates of seizure freedom, morbidity, and mortality associated with these techniques.
Topics: Electrodes, Implanted; Electroencephalography; Epilepsy; Humans; Intraoperative Neurophysiological Monitoring; Seizures; Stereotaxic Techniques; Treatment Outcome
PubMed: 31423575
DOI: 10.1111/epi.16315 -
Journal of Neurosurgery Jun 2016OBJECT Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of... (Meta-Analysis)
Meta-Analysis Review
OBJECT Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life. METHODS The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses. RESULTS The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30-2.34); an absence of headache (OR 1.77, 95% CI 1.04-3.25); peritumoral edema (OR 7.48, 95% CI 6.13-9.47); and non-skull base location (OR 1.77, 95% CI 1.04-3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants. CONCLUSIONS Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does not support routine use of prophylactic anticonvulsants in patients without seizures. Limitations associated with systematic review and meta-analysis should be considered when interpreting these results.
Topics: Humans; Meningioma; Seizures; Supratentorial Neoplasms
PubMed: 26636386
DOI: 10.3171/2015.4.JNS142742