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Neurocritical Care Feb 2022Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage (SAH). However, its efficacy, optimal dosing, and the adverse events associated with levetiracetam prophylaxis remain unclear.
METHODS
A systematic search of PubMed, Embase, and Cochrane central register of controlled trials (CENTRAL) database was conducted from January 1, 2000, to October 30, 2020, including articles addressing treatment with levetiracetam for seizure prophylaxis after SAH, ICH, TBI, and supratentorial neurosurgery. Non-English, pediatric (aged < 18 years), preclinical, reviews, case reports, and articles that included patients with a preexisting seizure condition or epilepsy were excluded. The coprimary meta-analyses examined first seizure events in (1) levetiracetam versus no antiseizure medication and (2) levetiracetam versus other antiseizure medications in all ICH, TBI, SAH, and supratentorial neurosurgery populations. Secondary meta-analyses evaluated the same comparator groups in individual disease populations. Risk of bias in non-randomised studies - of interventions (ROBINS-I) and risk-of-bias tool for randomized trials (RoB-2) tools were used to assess risk of bias.
RESULTS
A total of 30 studies (n = 6 randomized trials, n = 9 prospective studies, and n = 15 retrospective studies), including 7609 patients (n = 4737 with TBI, n = 701 with SAH, n = 261 with ICH, and n = 1910 with neurosurgical diseases) were included in analyses. Twenty-seven of 30 (90%) studies demonstrated moderate to severe risk of bias, and 11 of 30 (37%) studies used low-dosage levetiracetam (250-500 mg twice daily). In the primary meta-analyses, there were no differences in seizure events for levetiracetam prophylaxis (n = 906) versus no antiseizure medication (n = 2728; odds ratio [OR] 0.79, 95% confidence interval [CI] 0.53-1.16, P = 0.23, fixed-effect, I = 26%, P = 0.23 for heterogeneity) or levetiracetam (n = 1950) versus other antiseizure prophylaxis (n = 2289; OR 0.84, 95% CI 0.55-1.28, P = 0.41, random-effects, I = 49%, P = 0.005 for heterogeneity). Only patients with supratentorial neurosurgical diseases benefited from levetiracetam compared with other antiseizure medications (median 0.70 seizure events per-patient-year with levetiracetam versus 2.20 seizure events per-patient-year for other antiseizure medications, OR 0.34, 95% CI 0.20-0.58, P < 0.001, fixed-effects, I = 39%, P = 0.13 for heterogeneity). There were no significant differences in meta-analyses of patients with ICH, SAH, or TBI. Adverse events of any severity were reported in a median of 8% of patients given levetiracetam compared with 21% of patients in comparator groups.
CONCLUSIONS
Based on the current moderately to seriously biased heterogeneous data, which frequently used low and possibly subtherapeutic doses of levetiracetam, our meta-analyses did not demonstrate significant reductions in seizure incidence and neither supports nor refutes the use of levetiracetam prophylaxis in TBI, SAH, or ICH. Levetiracetam may be preferred post supratentorial neurosurgery. More high-quality randomized trials of prophylactic levetiracetam are warranted.
Topics: Adolescent; Anticonvulsants; Child; Humans; Levetiracetam; Prospective Studies; Retrospective Studies; Seizures
PubMed: 34286461
DOI: 10.1007/s12028-021-01296-z -
JAMA Oncology Nov 2016Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR)... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.
OBJECTIVE
To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM.
DATA SOURCES
Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015.
STUDY SELECTION
Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded.
DATA EXTRACTION AND SYNTHESIS
Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines.
MAIN OUTCOME AND MEASURES
Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year.
RESULTS
The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low.
CONCLUSION AND RELEVANCE
This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.
Topics: Brain; Brain Neoplasms; Disease-Free Survival; Glioblastoma; Humans; Risk; Treatment Outcome
PubMed: 27310651
DOI: 10.1001/jamaoncol.2016.1373 -
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 -
Surgical Neurology International 2022Hypertonic saline (HS) and mannitol are hyperosmolar agents that are usually used to reduce intracranial pressure (ICP) and provide a satisfactory brain relaxation. The... (Review)
Review
BACKGROUND
Hypertonic saline (HS) and mannitol are hyperosmolar agents that are usually used to reduce intracranial pressure (ICP) and provide a satisfactory brain relaxation. The aim of the study was to perform a systematic review and meta-analysis to compare the efficacy of HS and mannitol on brain relaxation intraoperatively in patient undergoing craniotomies for supra-tentorial brain tumors.
METHODS
A systematic review and meta-analysis of randomized control trials. We included randomized control trials that compared equiosmolar HS and mannitol in supratentorial tumors craniotomies and reported at least one of the following outcomes: degree of brain relaxation, ICP, central venous pressure, mean arterial pressure, perioperative fluid input, urine output, Na+ levels, and K+ levels. We searched Medline, Cochrane Central Register of Controlled Trials, and Embase using MESH terms and keywords. The bibliographic references of included studies and trial registries were also searched.
RESULTS
Seven articles were included. The degree brain of relaxation was comparable across the two groups with slight tendency toward HS (RR = 1.13, 95% CI 0.99-1.29; = 0.08). Mannitol was associated with significantly higher urine output (standardized mean difference [SMD] = -1.33, 95% CI -1.56--1.10; < 0.001). Na levels were higher in HS group (SMD = 1.47, 95% CI 0.86-2.09; < 0.001). Mannitol was associated with non-significant decrease in CVP and increase fluid input (SMD = 0.42, 95% CI 0.00-0.85 and SMD = -0.18, 95% CI -0.37-0.02, respectively).
CONCLUSION
Both HS and mannitol are associated with satisfactory brain relaxation with a non-statistically significant tendency for HS to achieve better relaxation scores with mannitol resulting in higher urine output while HS with higher Na levels.
PubMed: 35509546
DOI: 10.25259/SNI_136_2022 -
British Journal of Clinical Pharmacology Jul 2016The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients.
METHOD
A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects.
RESULTS
The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%).
CONCLUSIONS
The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.
Topics: Anticonvulsants; Craniotomy; Humans; Levetiracetam; Perioperative Care; Phenytoin; Piracetam; Seizures; Supratentorial Neoplasms; Valproic Acid
PubMed: 26945547
DOI: 10.1111/bcp.12926 -
World Neurosurgery May 2023Supratentorial hemangioblastomas are benign and highly vascularized neoplasms that appear most often in the spine and posterior cranial fossa. They can also be located... (Review)
Review
BACKGROUND
Supratentorial hemangioblastomas are benign and highly vascularized neoplasms that appear most often in the spine and posterior cranial fossa. They can also be located in the supratentorial compartment of the brain. We conducted a systematic review of the literature to better understand the clinical insights of supratentorial hemangioblastoma in adults.
METHODS
Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the authors reviewed the English-language literature in the PubMed/MEDLINE database on supratentorial hemangioblastoma in adults, published in the past 40 years. We analyzed the differences between sporadic hemangioblastomas and hemangioblastomas associated with von Hippel-Lindau disease. In addition, we compared the characteristics of supratentorial hemangioblastomas with infratentorial and spinal cord locations.
RESULTS
We reviewed 92 articles, describing 157 supratentorial hemangioblastomas in a total cohort of 148 adult patients. Most articles reporting supratentorial hemangioblastomas were published in the United States. Supratentorial hemangioblastomas occur more frequently in women than men. The median age at the time of diagnosis was 44.48 years. The sellar/parasellar region was the most commonly tumor location, while the most common morphological type was the solid type. Almost 80% of hemangioblastomas were completely resected; the outcome was favorable in more than 3 fourth of patients.
CONCLUSIONS
Given their rarity, the literature on supratentorial hemangioblastomas is limited and based mostly on case reports. Complete surgical resection is the first choice of treatment and is associated with a good treatment outcome.
Topics: Male; Adult; Humans; Female; Hemangioblastoma; Spinal Cord; von Hippel-Lindau Disease; Treatment Outcome; Brain; Spinal Cord Neoplasms; Magnetic Resonance Imaging
PubMed: 36822402
DOI: 10.1016/j.wneu.2023.02.071 -
Neurosurgical Review May 2023Neoadjuvant stereotactic radiotherapy (NaSRT) is a novel strategy for brain metastasis (BM) treatment, promising to achieve good local control, improved survival, and... (Meta-Analysis)
Meta-Analysis Review
Neoadjuvant stereotactic radiotherapy (NaSRT) is a novel strategy for brain metastasis (BM) treatment, promising to achieve good local control, improved survival, and low toxicity. This is a systematic review of available literature and meta-analysis of 8 articles eligible for inclusion after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases up to March 2023. A total of 484 patients undergoing NaSRT to treat 507 lesions were included. The median age was 60.9 (IQR 57-63) years, with a median tumor volume of 12.1 (IQR 9-14) cm. The most frequent histology was non-small-cell lung cancer (41.3%), followed by breast (18.8%), and melanoma (14.3%). Lesions had a preferred supratentorial location (77.4%). Most of the studies used a single fraction schedule (91% of patients, n = 440). Treatment parameters were homogeneous and showed a median dose of 18 (IQR 15.5-20.5) Gy at a median of 80% isodose. Surgery was performed after a median of 1.5 (IQR 1-2.4) days and achieved gross-total extent in 94% of cases. Median follow-up was 12.9 (IQR 10-15.7) months. NaSRT showed an overall mortality rate of 58% (95% CI 43-73) at the last follow-up. Actuarial outcomes rates were 60% (95% CI 55-64) for 1-year overall survival (1y-OS), 38% (95% CI 33-43) for 2y-OS, 29% (95% CI 24-34) for 3y-OS; overall 15% (95% CI 11-19) for local failure, 46% (95% CI 37-55) for distant brain failure, 6% (95% CI 3-8) for radionecrosis, and 5% (95% CI 3-8) for leptomeningeal dissemination. The median local progression-free survival time was 10.4 (IQR 9.5-11.4) months, while the median survival without distant failure was 7.4 (IQR 6.9-8) months. The median OS time for the entire cohort was 17 (IQR 14.9-17.9) months. Existing data suggest that NaSRT is effective and safe in the treatment of BMs, achieving good local control on BMs with and low incidence of radionecrosis and leptomeningeal dissemination. Distant control appears limited compared to other radiation regimens.
Topics: Humans; Middle Aged; Carcinoma, Non-Small-Cell Lung; Neoadjuvant Therapy; Lung Neoplasms; Brain Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 37256368
DOI: 10.1007/s10143-023-02031-2 -
World Neurosurgery Jul 2020Management of incidental asymptomatic brain tumors in children is controversial due to lack of clear evidence-based guidelines. We present this systematic review in an...
OBJECTIVES
Management of incidental asymptomatic brain tumors in children is controversial due to lack of clear evidence-based guidelines. We present this systematic review in an attempt to highlight an optimal treatment paradigm.
METHODS
This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Databases were searched up to August 2019 using the keywords "incidental," "brain tumor," and "pediatric." Our main focus was on brain lesions suspected for neoplasm, diagnosed incidentally on neuroimaging in an otherwise asymptomatic patient <18 years old. Cystic, vascular, and inflammatory brain lesions were excluded.
RESULTS
Fourteen studies comprising 308 patients were included. All cases were diagnosed using magnetic resonance imaging. The most common indications for imaging were headache (93; 30%) and trauma (72; 23%). Lesion distribution was supratentorial (179; 58%), infratentorial (121; 40%), and intraventricular (8; 3%). Of 308 cases, 243 (79%) were managed with neuroradiological surveillance and 57 (19%) by upfront surgical excision. Of those managed conservatively, 177 (73%) remained stable within a mean follow-up of 30 months, 54 (22%) progressed, and 12 (5%) spontaneously regressed. Meanwhile, upfront excision achieved complete remission in all 57 cases over a mean follow-up of 68.3 months.
CONCLUSION
A small body of evidence has emerged, highlighting the marked heterogeneity and contradictory results between the available studies, limiting our ability to draw solid conclusions. At this point, the decision between surgery and "watchful waiting" should be tailored on an individual patient basis depending on suspicion of malignancy, clinical or radiologic progression, and parental preference.
Topics: Adolescent; Asymptomatic Diseases; Brain Neoplasms; Child; Child, Preschool; Conservative Treatment; Disease Management; Humans; Incidental Findings; Infant; Infant, Newborn; Neurosurgery; Neurosurgical Procedures; Pediatrics; Watchful Waiting
PubMed: 32165344
DOI: 10.1016/j.wneu.2020.02.178 -
World Neurosurgery May 2023Historically, the occurrence of hemorrhage in the brainstem after an episode of supratentorial intracranial hypertension was described by Henri Duret in 1878.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Historically, the occurrence of hemorrhage in the brainstem after an episode of supratentorial intracranial hypertension was described by Henri Duret in 1878. Nevertheless, to date the eponym Duret brainstem hemorrhage (DBH) lacks systematic evidence regarding its epidemiology, pathophysiology, clinical and radiologic presentation, and outcome.
METHODS
We conducted a systematic literature review and meta-analysis using the Medline database from inception to 2022 looking for English-language articles concerning DBH, in accordance with the PRISMA guidelines.
RESULTS
The research yielded 28 articles for 32 patients (mean age, 50 years; male/female ratio, 3:1). Of patients, 41% had head trauma causing 63% of subdural hematoma, responsible for coma in 78% and mydriasis in 69%. DBH appeared on the emergency imaging in 41% and on delayed imaging in 56%. DBH was located in the midbrain in 41% of the patients, and in the upper middle pons in 56%. DBH was caused by sudden downward displacement of the upper brainstem secondary to supratentorial intracranial hypertension (91%), intracranial hypotension (6%), or mechanical traction (3%). Such downward displacement caused the rupture of basilar artery perforators. Brainstem focal symptoms (P = 0.003) and decompressive craniectomy (P = 0.164) were potential favorable prognostic factors, whereas an age >50 years showed a trend toward a poor prognosis (P = 0.0731).
CONCLUSIONS
Unlike its historical description, DBH appears as a focal hematoma in the upper brainstem caused by the rupture of anteromedial basilar artery perforators after sudden downward displacement of the brainstem, regardless of its cause.
Topics: Humans; Male; Female; Middle Aged; Cerebral Hemorrhage; Hematoma, Subdural; Brain Stem Hemorrhage, Traumatic; Intracranial Hypertension
PubMed: 36868404
DOI: 10.1016/j.wneu.2023.02.110 -
Cancers Sep 2022Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed... (Review)
Review
BACKGROUND
Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs.
METHODS
PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses.
RESULTS
We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm (range, 2.9-57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7-60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1-10) post-NaSRT. Median follow-up was 19.2-months (range, 1-41.3). Actuarial post-treatment rates were 4% (95%CI: 2-6%) for symptomatic radiation necrosis, 15% (95%CI: 12-18%) and 47% (95%CI: 42-52%) for local and distant recurrences, 6% (95%CI: 3-8%) for leptomeningeal metastases, 81% (95%CI: 75-87%) and 59% (95%CI: 54-63%) for 1-year local tumor control and overall survival.
CONCLUSION
NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.
PubMed: 36077863
DOI: 10.3390/cancers14174328