Factors Affecting Outcomes in Geriatric Traumatic Subdural Hematoma in a Neurosurgical Intensive Care Unit.

BACKGROUND AND OBJECTIVE: Geriatric patients (age ≥65 years) who sustain a traumatic brain injury have an increased risk of poor outcomes and higher mortality compared with younger cohorts. We aimed to evaluate the risk factors for discharge outcomes in a geriatric traumatic subdural hematoma population, stratified by age and pretraumatic medical comorbidities. This was a single-center retrospective cohort study of geriatric patients (N = 207). METHODS: Patient charts were evaluated for factors including patient characteristics, comorbidities, injury-related and seizure-related factors, neurosurgical intervention, and patient disposition on discharge. RESULTS: Bivariate and multivariate analyses showed that age was nonpredictive of patient outcomes. Underlying vasculopathic comorbidities were the primary determinant of posttraumatic seizure, surgical, and discharge outcomes. Multifactor analysis showed that patients who went on to develop status epilepticus (n = 11) had a higher frequency of vasculopathic comorbidities with strong predictive power in poor patient outcomes. CONCLUSIONS: Our findings suggest a need to establish unique prognostic risk factors based on patient outcomes that guide medical and surgical treatment in geriatric patients.

Refractory Elevated Intracranial Pressure (ICP) in the Setting of a Traumatic Cerebral Sinus Venous Thrombosis (CSVT).

The management of patients with elevated intracranial pressure (ICP) requires a systematic approach. After the failure of tier zero, tier one, and tier two therapies, all potential secondary causes of elevated ICP must be reviewed. Up to 28% of patients with blunt traumatic brain injury (TBI) develop cerebral sinus venous thrombosis (CSVT), among these, patients up to 55% have occlusive thrombi. A literature review revealed a dearth of specific treatment guidelines in this scenario. Here, we present one such case of refractory elevated ICP due to occlusive CSVT secondary to skull fractures. Initial CT venogram (CTV) on admission showed an occlusive CSVT; however, subsequent CTV on the post-trauma day (PTD) 4 and 6 showed non-occlusive thrombi only. The risks of worsening acute TBI-related hemorrhage with systemic anticoagulation versus the benefit of treating an occlusive CSVT are discussed here. In cases of occlusive CSVT with refractory elevated ICP and stable intracranial hemorrhage, the benefit of anticoagulation may outweigh the overall risks of hemorrhage expansion as prolonged uncontrolled ICP elevation is inevitably fatal. In this case, anticoagulation started on PTD 6, led to the resolution of ICP elevation and an excellent outcome for the patient, who was discharged to an acute rehab center, subsequently discharged home with no residual motor deficits, and was able to resume employment. Further prospective trials are necessary to develop guidelines for the management of occlusive CSVT in patients with severe TBI and to determine which patient populations are likely to benefit from early initiation of therapeutic anticoagulation.

Phase 2 trial of hypoxia activated evofosfamide (TH302) for treatment of recurrent bevacizumab-refractory glioblastoma.

Evofosfamide (Evo or TH302) is a hypoxia-activated prodrug which is reduced leading to the release of alkylating agent bromo-isophosphoramide mustard, which has shown safety and signals of efficacy in a prior phase 1 study in recurrent glioblastoma. We performed a dual center single-arm Phase II study to expand on the safety and efficacy of Evo plus bevacizumab in bevacizumab refractory glioblastoma. 33 patients with bevacizumab refractory GBM received Evo 670 mg/m2 in combination with Bevacizumab 10 mg/kg IV every 2 weeks. Assessments included adverse events, response, and survival. Median age of patients was 47 (range 19-76) and 24 (69%) were male. At the time of study entry, 9 (26%) had ongoing corticosteroid use. ECOG performance status was 0 or 1 in 83% of patients. Patients were mostly heavily pretreated with 77% have three or more prior regimens. A total of 12 patients (36%) suffered grade 3-4 drug associated adverse event (AE); no grade 5 AE were reported. Of the 33 evaluable patients, best response was PR in 3 (9%), SD in 14 (43%), and PD in 16 (48%) with responses confirmed by a second reviewer. Median time to progression of disease was 53 days (95% CI 42-113) and Median time to death was 129 days (95% CI 86-199 days). Progression free survival at 4 months (PFS-4) on Evo-Bev was 31%, which was a statistically significant improvement over the historical rate of 3%. The median overall survival of patients receiving Evo-Bevacizumab was 4.6 months (95% CI 2.9-6.6). The progression free survival of patients on Evo-Bevacizumab met the primary endpoint of progression free survival at 4 months of 31%, although the clinical significance of this may be limited. Given the patient population and Phase II design, these clinical outcomes will need further validation.