Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis

Abstract

Background: There is little information available on grey and white matter (GM and WM) atrophy in primary progressive multiple sclerosis (PPMS) and on their relationships with clinical and other magnetic resonance imaging (MRI) measures. Aim: To evaluate disease progression in the early phase of PPMS, focusing on axonal loss as assessed by volumetric MRI measures of WM and GM, and to determine their relationships with clinical outcomes and lesion load measures. Methods: Forty-three patients with PPMS within 5 years of symptom onset and 45 control subjects were studied. Three-dimensional brain scans were acquired and segmented into WM, GM, and cerebrospinal fluid (CSF) using SPM99. Brain parenchymal (BPF), WM (WMF), and GM fractions (GMF) normalized against total intracranial volumes were estimated. T2-weighted (T2) and enhancing lesion loads were also determined. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were recorded in all patients. Results: There were significant differences between patients and controls in BPF, WMF, and GMF values ( P < 0.001). BPF ( r = −0.469; P = 0.002) and WMF ( r = −0.532; P < 0.001) but not GMF ( r = −0.195; P = 0.2) correlated with EDSS scores. BPF ( r = 0.518; P = 0.001), WMF ( r = 0.483; P = 0.001), and GMF ( r = 0.337; P = 0.031) correlated with MSFC scores. Correlations with enhancing lesion and T2 loads were only significant for BPF and WMF. Conclusions: Brain atrophy is seen in the early stages of PPMS and affects both GM and WM. WM atrophy appears more closely related to clinical outcome and WM focal damage than GM atrophy in this patient group.