We aim to describe the outcomes after chronic subdural hematoma drainage (CSDH) management in a large cohort of patients on antithrombotic drugs, either antiplatelets or anticoagulants, at presentation and to inform clinical decision making on the timing of surgery and recommencement of these drugs. We used data from a previous UK-based multi-center, prospective cohort study. Outcomes included recurrence within 60 days, functional outcome at discharge, and thromboembolic event during hospital stay. We performed Cox regression on recurrence and multiple logistic regression on functional outcome. There were 817 patients included in the analysis, of which 353 (43.2%) were on an antithrombotic drug at presentation. We observed a gradual reduction in risk of recurrence for patients during the 6 weeks post-CSDH surgery. Neither antiplatelet nor anticoagulant drug use influenced risk of CSDH recurrence (hazard ratio, 0.93; 95% confidence interval [CI], 0.58-1.48; p = 0.76) or persistent/worse functional impairment (odds ratio, 1.08; 95% CI, 0.76-1.55; p = 0.66). Delaying surgery after cessation of antiplatelet drug did not affect risk of bleed recurrence. There were 15 in-hospital thromboembolic events recorded. Events were more common in the group pre-treated with antithrombotic drugs (3.3%) compared to the non-antithrombotic group (0.9%). Patients on an antithrombotic drug pre-operatively were at higher risk of thromboembolic events with no excess risk of bleed recurrence or worse functional outcome after CSDH drainage. The data did not support delaying surgery in patients on antithrombotic therapy. In the absence of a randomized controlled trial, early surgery and early antithrombotic recommencement should be considered in those at high risk of thromboembolic events.

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (Ktrans, ve and vp) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p < 0.001) and mean diffusivity (p < 0.001, repeated-measures ANOVA) with marked decreases in tumour microvascular parameters (p < 0.001, repeated-measures ANOVA). This study presents the first in vivo evaluation of alterations in the VS tumour microenvironment following SRS, demonstrating that changes in tumour sodium homeostasis and microvascular parameters can be imaged as early as 2 weeks following treatment. Future studies should seek to investigate these clinically relevant MRI metrics as early biomarkers of SRS response.

BACKGROUND:There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target.OBJECTIVE:To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS.METHODS:Immunostaining for Iba1 (macrophages), CD31 (endothelium), and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte-specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS.RESULTS:The Iba1+ cell count was significantly higher in growing as compared with static VS (592 vs 226/×20 HPF, P=<0.001). Similarly, the CD31+ % surface area was higher in growing VS (2.19% vs 1.32%, P = .01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2 = 0.263, P=<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS.CONCLUSION:There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a colinear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism.