Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors.

Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.

Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury.

OBJECTIVE Hypernatremia is independently associated with increased mortality in critically ill patients. Few studies have evaluated the impact of hypernatremia on early mortality in patients with severe traumatic brain injury (TBI) treated in a neurocritical care unit. METHODS A retrospective review of patients with severe TBI (admission Glasgow Coma Scale score ≤ 8) treated in a single neurocritical care unit between 1986 and 2012 was performed. Patients with at least 3 serum sodium values were selected for the study. Patients with diabetes insipidus and those with hypernatremia on admission were excluded. The highest serum sodium level during the hospital stay was recorded, and hypernatremia was classified as none (≤ 150 mEq/L), mild (151-155 mEq/L), moderate (156-160 mEq/L), and severe (> 160 mEq/L). Multivariate Cox regression analysis was performed to determine independent predictors of early mortality. RESULTS A total of 588 patients with severe TBI were studied. The median number of serum sodium measurements for patients in this study was 17 (range 3-190). No hypernatremia was seen in 371 patients (63.1%), mild hypernatremia in 77 patients (13.1%), moderate hypernatremia in 50 patients (8.5%), and severe hypernatremia in 90 patients (15.3%). Hypernatremia was detected within the 1st week of admission in 79.3% of patients (n = 172), with the majority of patients (46%) being diagnosed within 72 hours after admission. Acute kidney injury, defined as a rise in creatinine of ≥ 0.3 mg/dl, was observed in 162 patients (27.6%) and was significantly associated with the degree of hypernatremia (p < 0.001). At discharge, 148 patients (25.2%) had died. Hypernatremia was a significant independent predictor of mortality (hazard ratios for mild: 3.4, moderate: 4.4, and severe: 8.4; p < 0.001). Survival analysis showed significantly lower survival rates for patients with greater degrees of hypernatremia (log-rank test, p < 0.001). CONCLUSIONS Hypernatremia after admission in patients with severe TBI was independently associated with greater risk of early mortality. In addition to severe hypernatremia, mild and moderate hypernatremia were significantly associated with increased early mortality in patients with severe TBI.

Critical Care Management of the Patient with Traumatic Brain Injury.

The critical care management of patients with traumatic brain injury is complex. The primary goal is to minimize the effects of secondary injury that would otherwise serve to further worsen neurologic function. This requires an understanding of the abnormal brain physiology that is found in these patients. In this article the authors discuss this physiology and describe suggested treatment strategies for these patients based on evidence-based guidelines.

Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury.

BACKGROUND: Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. METHODS: The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. RESULTS: There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). CONCLUSION: Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. TRIAL REGISTRATION: NCT00313716 registered 4/2006.

Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial.

IMPORTANCE: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE: In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00313716.

Firearm-Related Traumatic Brain Injuries in Adults: A Scoping Review.

BACKGROUND AND OBJECTIVES: Firearm-related traumatic brain injury (TBI) has emerged as a significant public health issue in the United States, coinciding with a rapid increase in gun-related deaths. This scoping review aims to update our understanding of firearm-related TBI in adult populations. METHODS: A comprehensive search of 6 online databases yielded 22 studies that met the inclusion criteria. The reviewed studies predominantly focused on young adult men who were victims of assault, although other vulnerable populations were also affected. RESULTS: Key factors in evaluating patients with firearm-related TBI included low Glasgow Coma Scale scores, central nervous system involvement, hypotension, and coagulopathies at presentation. Poor outcomes in firearm-related TBIs were influenced by various factors, including the location and trajectory of the gunshot wound, hypercoagulability, hemodynamic instability, insurance status, and specific clinical findings at hospital admission. CONCLUSION: Proposed interventions aimed to reduce the incidence and mortality of penetrating TBIs, including medical interventions such as coagulopathy reversal and changes to prehospital stabilization procedures. However, further research is needed to demonstrate the effectiveness of these interventions. The findings of this scoping review hope to inform future policy research, advocacy efforts, and the training of neurosurgeons and other treating clinicians in the management of firearm-related TBI.

Endovascular Management of a Ruptured Aneurysm on a Posterior Inferior Cerebellar Artery with Extradural C2-Origin: Case Report and Literature Review.

Extracranial vascular pathology uncommonly causes intracranial subarachnoid hemorrhage (SAH). Among possible lesions are aneurysms at the craniocervical junction arising from a posterior inferior cerebellar artery (PICA) with an extradural origin. We describe a case of a 55-year-old female presenting with a sudden and severe headache. A computed tomography scan revealed a SAH within the fourth ventricle and cervical spinal canal, and a ruptured saccular aneurysm on a PICA with extradural C2-origin. Despite difficult access anatomy, endovascular treatment was feasible and resulted in subtotal initial occlusion and preservation of distal PICA flow. Upon 3-month follow-up, the aneurysm was completely occluded with a patent PICA. The patient's clinical status remained stable at the 1.5-year follow-up. In conclusion, we present a rare case of an aneurysm originating from a PICA with extradural C2-origin that was treated endovascularly with preservation of the PICA.

Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study.

Importance: Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. Objective: To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. Design, Setting, and Participants: This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Exposure: Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). Main Outcomes and Measures: The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. Results: A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). Conclusions and Relevance: This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study.

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. Level of evidence: IV. Trial registration number: NCT02119182.

HMG-CoA Reductase Inhibitors for Traumatic Brain Injury.

Traumatic brain injuries (TBIs) are associated with high morbidity and mortality due to both the original insult as well as the destructive biological response that follows. Medical management aims to slow or even halt secondary neurological injury while simultaneously laying the groundwork for recovery. Statins are one class of medications that is showing increased promise in the management of TBI. Used extensively in cardiovascular disease, these drugs were originally developed as competitive inhibitors within the cholesterol production pipeline. They are now used in diverse disease states due to their pleiotropic effects on other biological processes such as inflammation and angiogenesis. Preclinical studies, retrospective reviews, and randomized clinical trials have shown a variety of benefits in the management of TBI, but to date, no large-scale randomized clinical trial has been performed. Despite this limitation, statins' early promise and well-tolerated side effect profile make them a promising new tool in the management of TBIs. More bench and clinical studies are needed to delineate proper treatment regimens as well as understand their true potential.

Cerebral microdialysis and glucopenia in traumatic brain injury: A review.

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such measurements of cellular metabolism can yield critical missing information about a patient's physiologic state and help limit secondary damage. Glucose management in traumatic brain injury is still an unresolved question. As cerebral glucose metabolism may be uncoupled from systemic glucose levels due to the metabolic dysfunction, measurement of cerebral extracellular glucose concentrations could provide more predictive information and prove to be a better biomarker to avoid secondary injury of at-risk brain tissue. Based on data obtained from cerebral microdialysis, specific interventions such as ICP-directed therapy, blood glucose increment, seizure control, and/or brain oxygen optimization can be instituted to minimize or prevent secondary insults. Thus, microdialysis measurements of parenchymal metabolic function provides clinically valuable information that cannot be obtained by other monitoring adjuncts in the standard ICU setting.

The impact of a night float system on operative experience in neurosurgery residency.

OBJECTIVE: Since the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions in 2003, many residency programs have adopted a night float system to comply with time constraints. However, some surgical subspecialities have been concerned that use of a night float system deprives residents of operative experience. In this study, the authors describe their training program's transition to a night float system and its impact on resident operative experience. METHODS: The authors conducted a single-program study of resident surgical case volume before and after implementing the night float system at 3 of their 5 hospitals from 2014 to 2020. The authors obtained surgical case numbers from the ACGME case log database. RESULTS: Junior residents received a concentrated educational experience, whereas senior residents saw a significant decrease from 112 calls/year to 17. Logged cases significantly increased after implementation of the night float system (8846 vs 10,547, p = 0.04), whereas cases at non-night float hospitals remained the same. This increase was concurrent with an increase in hospital cases. This difference was mainly driven by senior resident cases (p = 0.010), as junior and chief residents did not show significant differences in logged cases (p > 0.40). Lead resident cases increased significantly after implementation of the night float system (6852 vs 8860, p = 0.04). When normalized for increased hospital cases, resident case increases were not statistically significant. CONCLUSIONS: Transitioning to a night float call system at the authors' institution increased overall resident operative cases, particularly for lead resident surgeons. Based on the results of this study, the authors recommend the use of a night float call system to consolidate night calls, which increases junior resident-level educational opportunities and senior resident cases.

Profiles of Cognitive Functioning at 6 Months After Traumatic Brain Injury Among Patients in Level I Trauma Centers: A TRACK-TBI Study.

Importance: Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known. Objective: To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers. Design, Setting, and Participants: This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023. Exposures: Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury. Main Outcomes and Measures: Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test). Results: The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups). Conclusions and Relevance: In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Neurolymphomatosis of the brachial plexus from atypical primary central nervous system lymphoma lesions: A case report and review of the literature.

Background: Primary central nervous system lymphoma (PCNSL) is an aggressive and extranodal non-Hodgkin lymphoma limited to the neuroaxis. In immunocompetent individuals, PCNSL is more common in older adults and lacks the association with the Epstein-Barr virus found in individuals with AIDS-associated PCNSL. Because the clinical presentation and radiographic findings of PCNSL are highly variable, stereotactic brain biopsy is typically required for definitive diagnosis. High-dose methotrexate, in combination with other chemotherapeutic agents with or without whole brain radiation, is the mainstay of treatment. Case Description: A 70-year-old HIV-negative woman presented with confusion, acute flaccid left arm weakness, and left hand numbness. Head computed tomography without contrast demonstrated a 1 cm hyperdense round lesion in the suprasellar cistern that prompted further evaluation. Gadolinium-enhanced brain magnetic resonance imaging demonstrated enhancing lesions with heterogeneous signal intensity in the suprasellar, pineal, and right periatrial regions that did not explain the limb weakness and numbness. Serum and cerebrospinal fluid (CSF) studies were unrevealing, and a diagnosis of PCNSL was made following stereotactic biopsy. The patient's liver cirrhosis precluded chemotherapy, but treatment with whole-brain radiation was pursued. Conclusion: The myriad clinical presentations and insidious course of PCNSL contribute to diagnostic difficulties, delays in treatment, and poor outcomes. Stereotactic brain biopsy is the primary method of PCNSL diagnosis since malignant cells are typically not detected in CSF. PCNSL should be considered in the differential diagnosis when immunocompetent elderly patients present with multiple intracranial lesions, even in the presence of lower motor neuron findings.

Racial and Socioeconomic Disparities in Patients With Meningioma: A Retrospective Cohort Study.

BACKGROUND: Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors. OBJECTIVE: To determine factors that contribute to different clinical outcomes in racial populations. METHODS: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences. RESULTS: Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival. CONCLUSION: Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes.

Intracranial Solitary Fibrous Tumor of the Skull Base: 2 Cases and Systematic Review of the Literature.

BACKGROUND: Intracranial solitary fibrous tumors (ISFTs) are rare neoplasms of mesenchymal origin that originate from the meninges. ISFTs of the skull base can be challenging to treat, as resection can be complicated by skull base anatomy. We present 2 cases of ISFT, the first manifesting with compressive cranial neuropathy from Meckel cave involvement and the second a posterior fossa lesion causing symptomatic hydrocephalus. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed database was queried with title/abstract keywords "intracranial," "solitary fibrous tumor," "hemangiopericytoma," "SFT," and "HPC." Search results were reviewed to exclude cases not involving the skull base. References from all selected articles were reviewed for potential additional cases. Patient demographic and clinical data from 58 identified skull base cases were collected for qualitative synthesis. RESULTS: Visual disturbances were the most common presenting symptom (30 cases, 52%) followed by headache (22 cases, 38%). The most common site of involvement was the sellar/parasellar region (18 cases, 31%) followed by middle fossa/temporal bone (14 cases, 24%). Resection was performed in 55 cases; gross total resection was reported in 26 cases (45%) and subtotal resection was reported in 21 cases (36%). Tumor recurrence was documented in 15 cases (26%) with median and mean follow-up periods of 16 and 29.9 months, respectively. CONCLUSIONS: We discuss presentation, imaging, histopathology, and management considerations for ISFTs while highlighting the potentially complex nature of skull base lesions and need for multidisciplinary approach to treatment.

Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study.

Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, Setting, and Participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures: TBI. Main Outcomes and Measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and Relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, Setting, and Participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main Outcomes and Measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and Relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI.

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.