Evidence of diffuse cerebellar neuroinflammation in multiple sclerosis by 11 C-PBR28 MR-PET

Activated microglia, which can be detected in vivo by C-PBR28 positron emission tomography (PET), represent a main component of MS pathology in the brain. Their role in the cerebellum is still unexplored, although cerebellar involvement in MS is frequent and accounts for disability progression. We aimed at characterizing cerebellar neuroinflammation in MS patients compared to healthy subjects by combining C-PBR28 MRI-Positron Emission Tomography (MR-PET) with 7 Tesla (T) MRI and assessing its relationship with brain neuroinflammation and clinical outcome measures. Twenty-eight MS patients and 16 healthy controls underwent C-PBR28 MR-PET to measure microglia activation in normal appearing cerebellum and lesions segmented from 7 T scans. Patients were evaluated using the Expanded Disability Status Scale and Symbol Digit Modalities Test. C-PBR28 binding was assessed in regions of interest using 60-90 minutes standardized uptake values normalized by a pseudo-reference region in the brain normal appearing white matter. Multilinear regression was used to compare tracer uptake in MS and healthy controls and assess correlations with clinical scores. In all cerebellar regions examined, MS patients showed abnormally increased tracer uptake, which correlated with cognitive and neurological disability. Neuroinflammation is widespread in the cerebellum of patients with MS and related to neurological disability and cognitive impairment.