CSF β-amyloid predicts early cerebellar atrophy and is associated with a poor prognosis in multiple sclerosis

Abstract

Background: Neurodegeneration is present from the earliest stages of multiple sclerosis (MS) and is critically involved in MS related clinical disability. Aim of the present study was to assess the connection between amyloid burden and early cerebellar grey matter (GM) atrophy compared to early brain GM atrophy in MS patients.

Methods: Forty newly diagnosed relapsing-remitting (RR-) MS patients were recruited. β-amyloid1-42 (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all subjects. All participants underwent neurological examination and brain magnetic resonance imaging (MRI) at baseline. Twenty-nine out of 40 patients repeated a brain MRI at 1-year follow-up. T1-weighted scans were segmented using the Voxel-Based Morphometry (VBM) protocol and the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12).

Results: Between-group comparison of cerebellar parenchymal fraction (GM+WM/total cerebellar volume%) showed significant differences between Aβ^high and Aβ^low at baseline (p < 0.0001) and follow-up (p = 0.02). Similarly, a between-group comparison of cerebellar GM fraction (GMF) showed significant differences between Aβ^high and Aβ^low at baseline (p = 0.002) and follow-up (p = 0.04). The multiple regression analysis showed CSF Aβ concentration as the best predictor of GMF both at baseline and over time (β = 0.505, β=0.377; p < 0.05). No significant results were found regarding global brain atrophy and CSF Aβ concentration.

Conclusions: Early cerebellar atrophy seems to be crucial in predicting a poor prognosis in MS, more than early global brain atrophy.

Keywords: Cerebellum; Multiple sclerosis; Progression; β-amyloid.