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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 -
Neurology India 2022New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. (Review)
Review
BACKGROUND
New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa.
OBJECTIVE
The aim of this study was to discuss the particularities of BD diagnosis in patients with posterior fossa lesions.
MATERIALS AND METHODS
The author made a systematic review of literature on this topic.
RESULTS AND CONCLUSIONS
A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions (i.e., cerebral hypoxia), the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions (i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum) may retain intracranial blood flow and EEG activity. In this article, I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also addressed Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to "Mother Talks" stimulus, rejecting the diagnosis of BD. Jahi McMath's MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find in some cases partial recovery of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.
Topics: Brain; Brain Death; Brain Diseases; Brain Stem; Humans; Intracranial Pressure
PubMed: 35532637
DOI: 10.4103/0028-3886.344634 -
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 -
Journal of Stroke and Cerebrovascular... Mar 2022Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium.
MATERIALS AND METHODS
We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status. We included papers in any language, through a combined search from January 2010 to June 2021. Case studies with less than 20 patients, case-control studies, and randomized controlled trials were excluded. MEDLINE, EMBASE, PsycINFO, CINAHL, and Alois databases were searched. Pooled relative risks were calculated using bivariate random effects models or network meta-analysis. Methodological quality was assessed across 8 factors.
RESULTS
31 patient samples representing 8329 patients were included. Delirium was more common in patients with supratentorial lesions than infratentorial (RR [Relative Risk] 2.01, CI [Confidence Interval] 1.49-2.72); anterior circulation lesions than posterior (RR 1.41, CI 1.13-1.78); and cortical lesions than subcortical (RR 1.54, CI 1.25-1.89). Stroke side was not associated with delirium (right vs. left: RR 0.99, CI 0.77-1.28). Delirium was more common in patients with hemorrhagic strokes than ischemic (RR 1.74, CI 1.42-2.11) and patients with preexisting qualitative atrophy (RR 1.66, CI 1.21-2.27).
CONCLUSION
Several brain localizations and types of strokes were associated with delirium. Conclusions were in part limited by the heterogeneity of studies and broad or qualitative lesion descriptions. These results may assist in anticipating the risk of delirium in acute stroke and highlight brain networks and pathologies that may be involved in the pathophysiology of delirium.
Topics: Delirium; Humans; Network Meta-Analysis; Risk; Stroke
PubMed: 34954599
DOI: 10.1016/j.jstrokecerebrovasdis.2021.106270 -
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 -
International Journal of Radiation... Jun 2024Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue... (Review)
Review
PURPOSE
Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.
METHODS AND MATERIALS
A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies.
RESULTS
Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD2; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD2 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46).
CONCLUSIONS
Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD2 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.
Topics: Humans; Re-Irradiation; Necrosis; Child; Neoplasm Recurrence, Local; Central Nervous System Neoplasms; Adolescent; Brain; Brain Stem; Ependymoma; Young Adult; Child, Preschool; Medulloblastoma; Radiation Injuries
PubMed: 38300187
DOI: 10.1016/j.ijrobp.2023.12.043 -
Annals of Neurology Aug 2020The effect of surgical treatment for supratentorial spontaneous intracerebral hemorrhage (ICH) and whether it is modified by key baseline characteristics and timing... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effect of surgical treatment for supratentorial spontaneous intracerebral hemorrhage (ICH) and whether it is modified by key baseline characteristics and timing remains uncertain.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials of surgical treatment of supratentorial spontaneous ICH aimed at clot removal. We searched MEDLINE, Embase, and Cochrane databases up to February 21, 2019. Primary outcome was good functional outcome at follow-up; secondary outcomes were death and serious adverse events. We analyzed all types of surgery combined and minimally invasive approaches separately. We pooled risk ratios with 95% confidence intervals and assessed the modifying effect of age, Glasgow Coma Scale, hematoma volume, and timing of surgery with meta-regression analysis.
RESULTS
We included 21 studies with 4,145 patients; 4 (19%) were of the highest quality. Risk ratio of good functional outcome after any type of surgery was 1.40 (95% confidence interval [CI] = 1.22-1.60, I = 46%, 20 studies), and after minimally invasive surgery it was 1.47 (95% CI = 1.26-1.72, I = 47%, 12 studies). For death, the risk ratio for any type of surgery was 0.77 (95% CI = 0.68-0.85, I = 23%, 21 studies), and for minimally invasive surgery it was 0.68 (95% CI = 0.56-0.83, I = 14%, 13 studies). Serious adverse events were reported infrequently. Surgery seemed more effective when performed sooner after symptom onset (p = 0.04, 12 studies). Age, Glasgow Coma Scale, and hematoma volume did not modify the effect of surgery.
INTERPRETATION
Surgical treatment of supratentorial spontaneous ICH may be beneficial, in particular with minimally invasive procedures and when performed soon after symptom onset. Further well-designed randomized trials are needed to demonstrate whether (minimally invasive) surgery improves functional outcome after ICH and to determine the optimal time window of the treatment after symptom onset. ANN NEUROL 2020;88:239-250.
Topics: Cerebral Hemorrhage; Humans; Minimally Invasive Surgical Procedures; Neurosurgical Procedures; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32239722
DOI: 10.1002/ana.25732 -
Cerebellum (London, England) Dec 2023To date, cerebellar contribution to language is well established via clinical and neuroimaging studies. However, the particular functional role of the cerebellum in... (Meta-Analysis)
Meta-Analysis Review
To date, cerebellar contribution to language is well established via clinical and neuroimaging studies. However, the particular functional role of the cerebellum in language remains to be clarified. In this study, we present the first systematic review of the diverse language symptoms in spoken language after cerebellar lesion that were reported in case studies for the last 30 years (18 clinical cases from 13 papers), and meta-analysis using cluster analysis with bootstrap and symptom co-occurrence analysis. Seven clusters of patients with similar language symptoms after cerebellar lesions were found. Co-occurrence analysis revealed pairs of symptoms that tend to be comorbid. Our results imply that the "linguistic cerebellum" has a multiform contribution to language function. The most possible mechanism of such contribution is the cerebellar reciprocal connectivity with supratentorial brain regions, where the cerebellar level of the language network has a general modulation function and the supratentorial level is more functionally specified. Based on cerebellar connectivity with supratentorial components of the language network, the "linguistic cerebellum" might be further functionally segregated.
Topics: Humans; Language; Cerebellum; Language Disorders; Linguistics; Brain; Magnetic Resonance Imaging
PubMed: 36205825
DOI: 10.1007/s12311-022-01482-5