Is contact sport participation associated with chronic traumatic encephalopathy or neurodegenerative decline? A systematic review and meta-analysis.

INTRODUCTION: We sought to evaluate a potential association between contact vs. non-contact sport participation and long-term neurologic outcomes and chronic traumatic encephalopathy (CTE). EVIDENCE ACQUISITION: PubMed/Embase/PsycINFO/CINAHL databases were queried for studies between 1950-2020 with contact and non-contact sports, longitudinal assessment >10 years, and long-term neurologic outcomes in four-domains: I) clinical diagnosis; II) CTE neuropathology; III) neurocognition; and IV) neuroimaging. EVIDENCE SYNTHESIS: Of 2561 studies, 37 met inclusion criteria, and 19 contained homogenous outcomes usable in the meta-analysis. Domain I: Across six studies, no significant relationship was seen between contact sport participation and antemortem diagnosis of neurodegenerative disease or death related to such a diagnosis (RR1.88, P=0.054, 95%CI0.99, 3.49); however, marginal significance (P<0.10) was obtained. Domain II: Across three autopsy studies, no significant relationship was seen between contact sport participation and CTE neuropathology (RR42.39, P=0.086, 95%CI0.59, 3057.46); however, marginal significance (P<0.10) was obtained. Domain III: Across five cognitive studies, no significant relationship was seen between contact sport participation and cognitive function on the Trail Making Test (TMT) scores A/B (A:d=0.17, P=0.275,95% CI-0.13, 0.47; B:d=0.13, P=0.310, 95%CI-0.12, 0.38). Domain IV: In 10 brain imaging-based studies, 32% comparisons showed significant differences between those with a history of contact sport vs. those without. CONCLUSIONS: No statistically significant increased risk of neurodegenerative diagnosis, CTE neuropathology, or neurocognitive changes was found to be associated with contact sport participation, yet marginal significance was obtained in two domains. A minority of imaging comparisons showed differences of uncertain clinical significance. These results highlight the need for longitudinal investigations using standardized contact sport participation and neurodegenerative criteria.

Predictors of Recurrence After Sub-total or Near-total Resection of Vestibular Schwannoma: Importance of Tumor Volume and Ventral Extension.

OBJECTIVE: To evaluate the predictors of remnant tumor regrowth and need for salvage therapy after less than gross total resection (GTR) of vestibular schwannoma (VS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary neurotologic referral center. PATIENTS: Patients who underwent VS resection between 2008 and 2019 either with GTR, near total resection (NTR), and subtotal resection (STR). INTERVENTIONS: Microsurgical resection, salvage radiosurgery. MAIN OUTCOME MEASURES: Regrowth free interval, salvage free interval, tumor doubling rate. RESULTS: Three hundred eighty five cases (GTR = 236, NTR = 77, and STR = 71) from 2008 to 2019 were included. STR cohort had much larger and complex tumors with significant differences in tumor volume, ventral extension and brainstem compression (p  < 0.001). On single predictor analysis, tumor volume, ventral extension, brainstem compression as well as STR strategy was associated with significant increased risk of regrowth and need for salvage therapy. Multivariate analysis revealed STR strategy as significant predictor of regrowth (hazard ratio 3.79, p  < 0.0005). Absolute remnant volume and extent of resection (EOR) did not predict regrowth. A small proportion of cases (NTR = 4%, STR = 15%) eventually needed salvage radiosurgery with excellent ultimate local tumor control with no known recurrence to date. CONCLUSIONS: Conservative surgical strategy employing NTR or STR can be employed safely in large and complex VS. While there is increased risk of regrowth in the STR cohort, excellent local control can be achieved with appropriate use of salvage radiosurgery. No disceret radiologic or operative predictors of regrowth were identified.

Impact of postoperative dexamethasone on survival, steroid dependency, and infections in newly diagnosed glioblastoma patients.

BACKGROUND: We examined the effect of dexamethasone prescribed in the initial 3 postoperative weeks on survival, steroid dependency, and infection in glioblastoma patients. METHODS: In this single-center retrospective cohort analysis, we electronically retrieved inpatient administration and outpatient prescriptions of dexamethasone and laboratory values from the medical record of 360 glioblastoma patients. We correlated total dexamethasone prescribed from postoperative day (POD) 0 to 21 with survival, dexamethasone prescription from POD30 to POD90, and diagnosis of an infection by POD90. These analyses were adjusted for age, Karnofsky performance status score, tumor volume, extent of resection, IDH1/2 tumor mutation, tumor MGMT promoter methylation, temozolomide and radiotherapy initiation, and maximum blood glucose level. RESULTS: Patients were prescribed a median of 159 mg [109-190] of dexamethasone cumulatively by POD21. Every 16-mg increment (4 mg every 6 hours/day) of total dexamethasone associated with a 4% increase in mortality (95% confidence interval [CI] 1%-7%, P < .01), 12% increase in the odds of being prescribed dexamethasone from POD30 to POD90 (95% CI 6%-19%, P < .01), and 10% increase in the odds of being diagnosed with an infection (95% CI, 4%-17%, P < .01). Of the 175 patients who had their absolute lymphocyte count measured in the preoperative week, 80 (45.7%) had a value indicative of lymphopenia. In the POD1-POD28 period, this proportion was 82/167 (49.1%). CONCLUSIONS: Lower survival, steroid dependency, and higher infection rate in glioblastoma patients associated with higher dexamethasone administration in the initial 3 postoperative weeks. Nearly half of the glioblastoma patients are lymphopenic preoperatively and up to 1 month postoperatively.

Predicting Discharge Disposition Following Meningioma Resection Using a Multi-Institutional Natural Language Processing Model.

BACKGROUND: Machine learning (ML)-based predictive models are increasingly common in neurosurgery, but typically require large databases of discrete variables for training. Natural language processing (NLP) can extract meaningful data from unstructured text. OBJECTIVE: To present an NLP model that predicts nonhome discharge and a point-of-care implementation. METHODS: We retrospectively collected age, preoperative notes, and radiology reports from 595 adults who underwent meningioma resection in an academic center from 1995 to 2015. A total of 32 algorithms were trained with the data; the 3 best performing algorithms were combined to form an ensemble. Predictive ability, assessed by area under the receiver operating characteristic curve (AUC) and calibration, was compared to a previously published model utilizing 52 neurosurgeon-selected variables. We then built a multi-institutional model by incorporating notes from 693 patients at another center into algorithm training. Permutation importance was used to analyze the relative importance of each input to model performance. Word clouds and non-negative matrix factorization were used to analyze predictive features of text. RESULTS: The single-institution NLP model predicted nonhome discharge with AUC of 0.80 (95% CI = 0.74-0.86) on internal and 0.76 on holdout validation compared to AUC of 0.77 (95% CI = 0.73-0.81) and 0.74 for the 52-variable ensemble. The multi-institutional model performed similarly well with AUC = 0.78 (95% CI = 0.74-0.81) on internal and 0.76 on holdout validation. Preoperative notes most influenced predictions. The model is available at http://nlp-home.insds.org. CONCLUSION: ML and NLP are underutilized in neurosurgery. Here, we construct a multi-institutional NLP model that predicts nonhome discharge.

Investigating Predictors of Increased Length of Stay After Resection of Vestibular Schwannoma Using Machine Learning.

OBJECTIVE: To evaluate the predictors of prolonged length of stay (LOS) after vestibular schwannoma resection. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Patients who underwent vestibular schwannoma resection between 2008 and 2019. INTERVENTIONS: Variables of interest included age, body mass index, comorbidities, symptoms, previous intervention, microsurgical approach, extent of resection, operative time, preoperative tumor volume, and postoperative complications. Predictive modeling was done through multivariable linear regression and random forest models with 80% of patients used for model training and the remaining 20% used for performance testing. MAIN OUTCOME MEASURES: LOS was evaluated as the number of days from surgery to discharge. RESULTS: Four hundred one cases from 2008 to 2019 were included with a mean LOS of 3.0 (IQR = 3.0-4.0). Postoperatively, 14 (3.5%) of patients had LOS greater than two standard deviations from the mean (11 days). In a multivariate linear regression model (adjusted R2 = 0.22; p < 0.001), preoperative tumor volume (p < 0.001), coronary artery disease (p = 0.002), hypertension (p = 0.029), and any major complication (p < 0.001) were associated with increased LOS (by 0.12, 3.79, 0.87, and 3.20 days respectively). A machine learning analysis using a random forest identified several potential nonlinear relationships between LOS and preoperative tumor dimensions (length, volume) and operative time that were not captured on regression. The random forest model had lower prediction error compared to the regression model (RMSE 5.67 vs. 44.59). CONCLUSIONS: Tumor volume, coronary artery disease, hypertension, and major complications impact LOS. Machine learning methods may identify nonlinear relationships worthy of targeted clinical investigation and allow for more accurate patient counseling.

Antiepileptic Drugs in the Management of Cerebral Metastases.

Seizures represent a common and debilitating complication of central nervous system metastases. The use of prophylactic antiepileptic drugs (AEDs) in the preoperative period remains controversial, but the preponderance of evidence suggests that it is not helpful in preventing seizure and instead poses a significant risk of adverse events. Studies of postoperative seizure prophylaxis have not shown substantial benefit, but this practice remains widespread. Careful analysis of the risk of seizure based on patient-specific factors, such as tumor location and primary tumor histology, should guide the physician's decision on the initiation and cessation of prophylactic AED therapy.

Secondary malignancy following stereotactic radiosurgery for benign neurologic disease: A cohort study and review of the literature.

Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife® or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.

Deep brain stimulation in pediatric dystonia: a systematic review.

While deep brain stimulation (DBS) treatment is relatively rare in children, it may have a role in dystonia to reduce motor symptoms and disability. Pediatric DBS studies are sparse and limited by small sample size, and thus, outcomes are poorly understood. Thus, we performed a systematic review of the literature including studies of DBS for pediatric (age < 21) dystonia. Patient demographics, disease causes and characteristics, motor scores, and disability scores were recorded at baseline and at last post-operative follow-up. We identified 19 studies reporting DBS outcomes in 76 children with dystonia. Age at surgery was 13.8 ± 3.9 (mean ± SD) years, and 58% of individuals were male. Post-operative follow-up duration was 2.8 ± 2.8 years. Sixty-eight percent of patients had primary dystonia (PD), of whom 56% had a pathological mutation in DYT1 (DYT1+). Across all patients, regardless of dystonia type, 43.8 ± 36% improvement was seen in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (-M) scores after DBS, while 43.7 ± 31% improvement was observed in BFMDRS disability (-D) scores. Patients with PD were more likely to experience ≥ 50% improvement (56%) in BFMDRS-M scores compared to patients with secondary causes of dystonia (21%, p = 0.004). DYT1+ patients were more likely to achieve ≥ 50% improvement (65%) in BFMDRS-D than DTY1- individuals (29%, p = 0.02), although there was no difference in BFMDRS-M ≥ 50% improvement rates between DYT1+ (66%) or DYT1- (43%) children (p = 0.11). While DBS is less common in pediatric patients, individuals with severe dystonia may receive worthwhile benefit with neuromodulation treatment.