Evidence for inflammation in normal appearing brain regions in patients with growing sporadic vestibular schwannoma: a PET study

Non-auditory symptoms can be a prominent feature in patients with sporadic vestibular schwannoma (VS), but the cause of these symptoms is unknown. Inflammation is hypothesized to play a key role in the growth and symptomatic presentation of sporadic VS, and in this study we investigated through translocator protein (TSPO) PET whether inflammation occurred within the ‘normal appearing’ brain of such patients and its association with tumor growth. Dynamic PET datasets from fifteen patients with sporadic VS (8 static, 7 growing) who had been previously imaged using the TSPO tracer [11C](R)-PK11195 were included. Parametric images of [11C](R)-PK11195 binding potential (BPND) and the distribution volume ratio (DVR) were derived and compared across VS growth groups within both contralateral and ipsilateral grey (GM) and white-matter (WM) regions. Voxel-wise cluster analysis was additionally performed to identify anatomical regions of increased [11C](R)-PK11195 binding. Compared with static tumors, growing VS demonstrated significantly higher cortical (GM, 1.070 vs 1.031, p = 0.03) and whole brain (GM&WM,1.045 vs 1.006, p = 0.03) [11C](R)-PK11195 DVR values. Voxel-wise analysis supported the region-based analysis and revealed clusters of high TSPO binding within the precentral, postcentral, and prefrontal cortex in patients with growing VS. We present the first in vivo evidence of increased TSPO expression and inflammation within the brains of patients with growing sporadic VS. These results provide a potential mechanistic insight into the development of non-auditory symptoms in these patients and highlight the need for further studies interrogating the role of neuroinflammation in driving VS symptomatology.