Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.

BACKGROUND: Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival. METHODS: Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays. RESULTS: High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas. CONCLUSIONS: GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.

Homology Modeling, Molecular Dynamics Simulation, and Prediction of Bovine TLR2 Heterodimerization.

Toll-like receptor 2 (TLR2) is a major membrane-bound receptor with ligand and species specificity that activates the host immune response. Heterodimerization of TLR2 with TLR1 (TLR2/1) or TLR6 (TLR2/6), triggered by ligand binding, is essential to initiating the signaling pathway. Bovine TLR2 (bTLR2) heterodimerization has not been defined yet compared with human and mouse TLR2s (hTLR2 and mTLR2). The aim of the present study was to model bovine TLRs (TLRs 1, 2 and 6) and create the heterodimeric forms of the bovine TLR2 using molecular dynamics (MD) simulations. We compared the intermolecular interactions in bTLR2/1-PAM3 and bTLR2/6-PAM2 with the hTLR2 and mTLR2 complexes through docking simulations and subsequent MD analyses. The present computational findings showed that bTLR2 dimerization could have a biological function and activate the immune response, similar to hTLR2 and mTLR2. Agonists and antagonists that are designed for hTLR2 and mTLR2 can target bTLR2. However, the experimental approaches to comparing the functional immune response of TLR2 across species were missing in the present study. This computational study provides a structural analysis of the bTLR2 interaction with bTLR1 and bTLR6 in the presence of an agonist/antagonist and reveals the three-dimensional structure of bTLR2 dimerization. The present findings could guide future experimental studies targeting bTLR2 with different ligands and lipopeptides.

Lesion network mapping of ectopic craniopharyngioma identifies potential cause of psychosis: a case report.

We report the case of a patient with craniopharyngioma who demonstrated ectopic spread to the right temporal lobe and concurrent local recurrence, 10 years after her initial diagnosis. The patient additionally demonstrated new-onset psychotic symptoms of uncertain etiology during her admission. Lesion network mapping identified the ectopic lesion as a putative cause for her psychosis. These findings were substantiated after the resection of the ectopic lesion and subsequent resolution of her psychiatric symptoms. This report adds to the rare accounts of ectopic craniopharyngioma, while highlighting the utility of network-based analyses in peri-operative tumor evaluation and the assessment of atypical neuropsychiatric phenomena.

Atonic seizures in children: a meta-analysis comparing corpus callosotomy to vagus nerve stimulation.

PURPOSE: Atonic seizures are associated with a particularly poor response to medical treatment. We performed a systematic review and meta-analysis to compare the efficacy of corpus callosotomy (CC) and vagus nerve stimulation (VNS) in the management of atonic seizures in the pediatric population. METHODS: A literature search was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations, focusing on atonic seizures, CC, and VNS in pediatric populations. Pertinent clinical data were extracted and analyzed. Pooled effects between groups were calculated as standardized error (SE) with 95% confidence intervals (CIs). To assess for statistical significance, the Z-test was performed, using the pooled effect size (ES) and 95% CI for each intervention. RESULTS: A total of 31 studies met the inclusion criteria, with 24 studies encompassing 425 children treated with CC and 7 studies encompassing 108 children treated with VNS. Twenty-four studies were included in a meta-analysis. There was a statistically significant difference in the primary outcome of atonic seizure control in favor of CC (overall effect size (ES) 0.73, 95% CI 0.69-0.77 for CC, ES 0.4, 95% CI 0.28-0.51 for VNS, p = 0.003). There was a higher rate of complications requiring reoperation in the CC cohort (6.6% vs. 3.8%) and a 14% rate of symptomatic disconnection syndrome. CONCLUSIONS: While both techniques are safe, CC provides a much higher chance of effectively managing this morbid seizure type albeit with a higher risk of re-operation and disconnection syndrome.

Cross-national disparities contribute to heterogeneity in patient outcomes following invasive monitoring: A hierarchical mixed-effects analysis.

There is substantial variability in outcomes following invasive monitoring and surgical treatment of drug-resistant epilepsy (DRE). Patients with DRE are uniquely vulnerable to cross-national health care disparities, as their epilepsy is difficult to treat and requires extensive resources. In a large cross-national database of patients undergoing invasive monitoring for epilepsy surgery, we sought to evaluate the association between social, economic, and educational indicators of the country of treatment and patient outcomes following invasive monitoring. We performed a mixed-effects analysis of an individual patient database of 595 subjects enrolled in 33 studies encompassing 25 neurosurgical centers in 10 countries of invasive monitoring for epilepsy from 1996 to 2019. Upon preliminary univariate analysis, significant nation-level predictors of seizure outcome following either stereoelectroencephalography or subdural electrodes were hospital beds per 100,000 population, physician density, gross domestic product (GDP) growth, male and female educational attainment, and unemployment rate. On multivariate mixed-effects logistic regression, physician density (ß = -0.5112, P<.00697) and GDP growth (ß = 0.53822, P<.00404) were the only nation-level covariates of significance associated with seizure outcome. A higher physician density was associated with lesser seizure freedom rates, whereas higher GDP growth was associated with greater seizure freedom rates. Although patient-specific variables were the primary determinant of seizure outcomes, cross-national disparities also contribute to heterogeneities. Our findings highlight the importance of a systems-level dialogue to improve surgical outcomes for DRE patients.

Patient phenotypes and clinical outcomes in invasive monitoring for epilepsy: An individual patient data meta-analysis.

OBJECTIVE: Invasive monitoring provides valuable clinical information in patients with drug-resistant epilepsy (DRE). However, there is no clear evidence indicating either stereoelectroencephalography (SEEG) or subdural electrodes (SDE) as the optimal method. Our goal was to examine differences in postresection seizure freedom rates between SEEG- and SDE-informed resective epilepsy surgeries. Additionally, we aimed to determine potential clinical indicators for SEEG or SDE monitoring in patients with drug-resistant epilepsy. METHODS: A systematic literature review was performed in which we searched for primary articles using keywords such as "electroencephalography", "intracranial grid", and "epilepsy." Only studies containing individual patient data (IPD) were included for analysis. A one-stage IPD meta-analysis was performed to determine differences in rates of seizure freedom (International League Against Epilepsy (ILAE) guidelines and Engel classification) and resection status between SEEG and SDE patients. A Cox proportional-hazards regression was performed to determine the effect of time on seizure freedom status. Additionally, a principal component analysis was performed to investigate primary drivers of variance between these two groups. RESULTS: This IPD meta-analysis compared differences between SEEG and SDE invasive monitoring techniques in 595 patients from 33 studies. Our results demonstrate that while there was no difference in seizure freedom rates regardless of resection (p = 0.0565), SEEG was associated with a lower rate of resection compared with SDE (82.00% SEEG, 92.74% SDE, p = 0.0002). Additionally, while SDE was associated with a higher rate of postresection seizure freedom (54.04% SEEG, 64.32% SDE, p = 0.0247), the difference between seizure freedom rates following SEEG- or SDE-informed resection decreased with long-term follow-up. A principal component analysis showed that cases resulting in SEEG were associated with lower risk of morbidity than SDE cases, which were strongly collinear with multiple subpial transections, anterior temporal lobectomy, amygdalectomy, and hippocampectomy. SIGNIFICANCE: In this IPD meta-analysis of SEEG and SDE invasive monitoring techniques, SEEG and SDE were associated with similar rates of seizure freedom at latest follow-up. The former was associated with lower rates of resection. Furthermore, the clinical phenotypes of patients undergoing SEEG monitoring was associated with lower rates of complications. Future long-term prospective registries of IPD are promising options for clarifying the differences in these intracranial monitoring techniques as well as the unique patient phenotypes that may be associated with their indication.

The Cost-Effectiveness of 5-ALA in High-Grade Glioma Surgery: A Quality-Based Systematic Review.

BACKGROUND: High-grade gliomas (HGGs) are aggressive tumors that inevitably recur due to their diffusely infiltrative nature. Intraoperative adjuncts such as 5-aminolevulinic acid (5-ALA) have shown promise in increasing extent of resection. As the prospect of increased use of 5-ALA rises, a systematic overview of the health economics of this adjunct is critical. METHODS: Medline, EMBASE, Centre for Reviews and Dissemination, EconPapers, and Cochrane databases were searched for keywords relating to glioma, cost-effectiveness, and 5-ALA. Primary studies reporting on the health economics or cost-effectiveness of 5-ALA compared to white light surgery in HGG were included. Quality was assessed using the British Medical Journal guidelines. RESULTS: Three studies were identified. All were European and conducted from the perspective of national healthcare systems. Two studies demonstrated the cost-utility of 5-ALA compared to white light (C$12,817 and C$13,508/quality-adjusted life-years (QALYs)). One assessed the cost-utility per gross total resection (C$6,813). Both these values were below the national cost-effectiveness thresholds for each respective study. The third study demonstrated no significant difference in cost of 5-ALA in glioblastoma resection (C$14,732) compared to prior to its routine use (C$15,936). The quality of these studies ranged from moderate to average. None of these studies considered patient perspective or indirect costs in their analysis. CONCLUSIONS: Growing evidence exists examining the health economic benefit of 5-ALA as an intraoperative adjunct for HGG resection. Additional studies within the Canadian context using 5-ALA, specifically incorporating patient and societal perspectives into the cost-utility analyses, are necessary to solidify this line of evidence.

Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure: A Systematic Review and Meta-analysis.

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485).

Method of invasive monitoring in epilepsy surgery and seizure freedom and morbidity: A systematic review.

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.

Exploring the expectation-actuality discrepancy: a systematic review of the impact of preoperative expectations on satisfaction and patient reported outcomes in spinal surgery.

Quality in healthcare is increasingly graded through a patient-centric lens, using reports of satisfaction and self-perceived outcome. Preestablished expectations have been recognized to influence these measures. With this review, we aim to examine the impact of expectations on satisfaction and patient-reported outcomes (PRO) for individuals undergoing elective spine surgery. We systematically searched MEDLINE, EMBASE, CINAHL, and Cochrane Library electronic databases from inception to July 2015 for studies examining the relationship between expectations and satisfaction/PROs in the context of elective spinal surgery. Qualitative synthesis centered around three key questions: (1) Does the magnitude of preoperative expectations impact patient satisfaction and/or PRO after surgery? (2) Does the underlying spinal pathology influence this relationship? (3) What is the impact of unmet expectations on satisfaction? A total of 1489 citations were retrieved. Nineteen met our inclusion criteria. These comprised 3383 patients; 3200 had lumbar and only 183 had cervical spine surgery. Three findings prevailed: (1) high preoperative expectations appear to be associated with higher satisfaction and PROs after surgery for focal lumbar disc herniation, but not for lumbar spinal stenosis; (2) patient expectations frequently exceed actual outcome, creating an "expectation-actuality discrepancy" (E-AD); and (3) high-quality studies suggest a larger E-AD portends lower satisfaction. Limitations to the data include heterogeneous study populations and surgical indications, along with the use of non-validated assessment tools, particularly for satisfaction. Our findings highlight the potential importance of establishing realistic expectations prior to surgery and may serve to direct future research efforts.

Neurofibromatosis Clinic: A Report on Patient Demographics and Evaluation of the Clinic.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common single-gene disorder. A multidisciplinary approach to the management of NF1 patients is necessitated by the heterogeneity of clinical manifestations. Although multidisciplinary paediatric clinics have been well established, there is a dearth of such resources for adults with NF1. Herein we report our one-year institutional experience with a multidisciplinary adult NF1 clinic. METHODS: A multidisciplinary team was assembled, and an NF Patient Registry Initiative questionnaire was adapted to collect patient-reported data during clinics. Multiple databases were searched to identify publications pertaining to the experience of other multidisciplinary NF1 clinics focusing on adult patients. Data on patient epidemiology and clinical staff were compared to our data. RESULTS: A total of 77 patients were scheduled, and 68 attended the clinic, of whom 66 completed the intake questionnaire. The demographic and clinical data from this Canadian population are mostly consistent with previous reports, with some exceptions. Clinical data related to immune system involvement such as asthma, airway/breathing-related difficulties or allergies were striking in our NF1 population. Six relevant published reports of other NF1 clinics were identified. Reports from these studies pertained to periods ranging from 10 to 38 months, and the number of adults assessed ranged from 19 to 177 patients. CONCLUSIONS: The structure of our clinic and the patient volume are comparable to those of other established centres found in the literature. Our data offer valuable cross-sectional prevalence statistics in the Canadian population. The patient-reported data concerning involvement of the immune system contribute to an emerging recognized medical concern within the NF1 population and warrant further clinical and basic investigation.

National Perspectives on the Training of Neurosurgery Residents in Stereotactic Radiosurgery.

BACKGROUND: Despite the critical role played by neurosurgeons in performing radiosurgery, neurosurgery residents in Canada have limited exposure to radiosurgery during their training. A survey of neurosurgery residents and faculty along with radiation oncology faculty was conducted to analyze perspectives regarding incorporating formal radiosurgery training into the neurosurgery residency curriculum Methods: An online survey platform was employed. Descriptive statistics were used to summarize center and respondent characteristics. Categorical variables were compared using odds ratios and corresponding 95% confidence intervals. The chi-squared test was utilized to assess statistical significance. A value of p<0.05 was considered significant Results: The response rate was 31% (119/381); 87% (102/119) of respondents were from the neurosurgical specialty and 13% (17/119) from radiation oncology. Some 46% of residents (18/40) were "very uncomfortable" with radiosurgery techniques, and 57% of faculty (42/73) believed that dedicated radiosurgery training would be beneficial though impractical. No respondents felt that "no training" would be beneficial. A total of 46% of residents (19/41) felt that this training would be beneficial and that time should be taken away from other rotations, if needed, while 58% of faculty (42/73) and 75% (28/41) of residents believed that either 1 or 1-3 months of time dedicated to training in radiosurgery would suffice Conclusions: Canadian neurosurgeons are actively involved in radiosurgery. Despite residents anticipating a greater role for radiosurgery in their future, they are uncomfortable with the practice. With the indications for radiosurgery expanding, this training gap can have serious adverse consequences for patients. Considerations regarding the incorporation and optimal duration of dedicated radiosurgery training into the Canadian neurosurgery residency curriculum are necessary.

The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review.

5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society.

Cervical spine clearance in obtunded patients after blunt traumatic injury: a systematic review.

BACKGROUND: Cervical spine clearance protocols are controversial for unconscious patients after blunt traumatic injury and negative findings on computed tomography (CT). PURPOSE: To review evidence about the utility of different cervical spine clearance protocols in excluding significant cervical spine injury after negative CT results in obtunded adults with blunt traumatic injury. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library were searched from January 2000 through November 2014. STUDY SELECTION: English-language studies that examined patients with negative CT results having confirmatory routine testing with magnetic resonance imaging (MRI), dynamic radiography, or clinical examination and that reported outcome measures of missed cervical spine injury, need for operative stabilization, or prolonged use of cervical collars. DATA EXTRACTION: Independent reviewers evaluated the quality of studies and abstracted the data according to a predefined protocol. DATA SYNTHESIS: Of 28 observational studies (3627 patients) that met eligibility criteria, 7 were prospective studies (1686 patients) with low risk of bias and well-interpreted, high-quality CT scans. These 7 studies showed that 0% of significant injuries were missed after negative CT results. The overall studies using confirmatory routine testing with MRI showed incidence rates of 0% to 1.5% for cervical spine instability (16 studies; 1799 patients), 0% to 7.3% for need for operative fixation (17 studies; 1555 patients), and 0% to 29.5% for prolonged collar use (16 studies; 1453 patients). LIMITATIONS: Most studies were retrospective. Approaches to management of soft tissue changes with collars varied markedly. CONCLUSION: Cervical spine clearance in obtunded adults after blunt traumatic injury with negative results from a well-interpreted, high-quality CT scan is probably a safe and efficient practice. PRIMARY FUNDING SOURCE: None.

A Propensity Score-Matched Study of the Use of Non-steroidal Anti-inflammatory Agents Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Inflammation may contribute to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Here, we compared outcomes among propensity score-matched cohorts who did and did not receive non-steroidal anti-inflammatory drug (NSAID) use after aSAH. METHODS: Propensity score-matched analysis of 413 subjects enrolled in the Clazosentan to Overcome Neurological iSChemia and Infarction OccUring after Subarachnoid hemorrhage (CONSCIOUS-1) study. Propensity score matching was performed on the basis of age, sex, baseline National Institutes of Health Stroke Scale score, World Federation of Neurological Societies grade on admission, procedure used for securing aneurysm, and SAH clot burden. RESULTS: 178 patients were matched (89 received NSAIDs, 89 did not). Propensity score matching was considered acceptable. Patients who had received NSAIDs during their hospital stay had significantly lower mortality rate, and reduced duration of intensive care unit stay and total length of hospital stay (P = 0.035, P = 0.009, and P = 0.053, respectively). At 6 weeks, 80.9 % of patients treated with NSAIDs had good functional outcome compared to 68.5 % of matched controls (P = 0.083). There was no significant difference in the proportions of patients who developed delayed ischemic neurological deficits, angiographic vasospasm, or required rescue therapy. CONCLUSIONS: Inflammation may play a crucial role in the poor outcomes after SAH, and that NSAIDs may be a useful therapeutic option, once validated by larger prospective studies.

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the quality of design/reporting of RCTs in neuro-oncology persist. Quality improvement is necessary. Consideration of alternative strategies should be considered.

Clinical outcomes of MR-guided laser interstitial thermal therapy corpus callosum ablation in drug-resistant epilepsy: a systematic review and meta-analysis.

OBJECTIVE: The goal of this systematic review and meta-analysis was to provide an updated analysis of studies investigating outcomes, morbidity, and mortality associated with MR-guided laser interstitial thermal therapy (MRgLITT) corpus callosum ablation (CCA). METHODS: Study inclusion criteria for screening required that studies report on human subjects only, including patients aged 1-52 years diagnosed with drug-resistant epilepsy who underwent CCA. Sixteen articles published between 2016 and 2023 were included for the systematic review and analysis, including 4 case reports, 11 case series, and 1 case-control study. Altogether, 85 pediatric and adult patients undergoing CCA were included in the systematic review (46 patients younger and 39 patients older than 21 years). The main outcome of seizure freedom was measured using the decrease in the frequency of atonic seizures following surgery, percentage of atonic seizure freedom following surgery, and percentage of overall seizure freedom following surgery. These measurements were made using data from the last follow-up for patients with at least 6 months of follow-up post-CCA. RESULTS: The extent of CCA differed across the pooled cohorts, including anterior two-thirds CCA (38.89%, n = 35) and posterior one-third CCA for completion of a prior partial CCA (22.22%, n = 20), complete CCA (27.78%, n = 25), or CCA of residual white matter in the case of subtotal initial ablation (5.56%, n = 5). Overall, 12.94% of the patients undergoing CCA experienced operational complications. The most common operative complications across 90 CCA operations were probe malpositioning (n = 6), hemorrhage (n = 5), off-target extension of splenium ablation to the thalamus (n = 1), infection (n = 1), and postoperative CSF leak (n = 1). Neurological deficits following CCA were reported as transient in 18.82% and permanent in 4.71% of patients across all studies. The most common neurological deficits were disconnection syndrome (n = 4) or transient hemiplegia (supplementary motor area-like syndrome; n = 4). The 6-month overall seizure freedom rate was 18.87% of 53 patients, and the atonic seizure freedom rate was 46.28% of 52 patients postoperatively. CCA resulted in an average decrease in atonic seizure rate from 8.30 to 1.65 atonic seizures per day (average decrease 80.12%). CONCLUSIONS: CCA is associated with an acceptable complication profile, and most patients experience a meaningful reduction in target seizure semiologies. Accurate MRgLITT probe placement is likely important for maximizing CCA while avoiding collateral damage. Avoidable complications of CCA include off-target ablation (and associated deficits), hemorrhage, and future surgery for residual CCA to palliate continued seizures.

The Prevalence of Seizures in Brain Metastasis Patients on Anticonvulsant Prophylaxis: A Systematic Review and Meta-Analysis.

BACKGROUND: Brain metastasis (BM) prognosis is incredibly poor and is often associated with considerable morbidity. Seizures are commonly present in these patients, and their biopsychosocial impact can be dangerous. The use of antiepileptic drugs (AEDs) as primary prophylaxis remains controversial. This systematic review and meta-analysis aim to evaluate the efficacy of AED prophylaxis in patients with BM. METHODS: MEDLINE via PubMed, Web of Science, EMBASE, and Cochrane were searched for articles pertinent to AED prophylaxis use in patients with BM. Patients with BM previously treated for cancer who were seizure naive at the time of inclusion were included. Data regarding patient characteristics, type of AED, prior treatments, and groups at a high risk of seizure were extracted. Seizure prevalence was obtained. RESULTS: Eight studies were included in this systematic review and meta-analysis; 1902 total patients with BM were included, with 381 receiving antiepileptic prophylaxis, and 1521 receiving no prophylaxis. Although the odds of a seizure in the treatment group was found to be 1.158 times the odds of a seizure in the control group, the odds ratio was not statistically significant (t-statistic = 0.62, P value = 0.5543). CONCLUSIONS: There was no significant difference in the odds of seizure development in control groups compared to patients receiving prophylactic antiepileptic therapy. As patients with BM present with heterogeneity in tumor characteristics and receive various treatment modalities, future research is needed to identify groups that may benefit more significantly from AED prophylaxis.