MR-morphometry in multiple system atrophy and sporadic adult onset ataxias of unknown aetiology – different approaches

Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by neurodegeneration in basal ganglia, brainstem, cerebellum and intermediolateral cell columns of the spinal cord. Clinically, a parkinsonian (MSA-P) and a cerebellar type of MSA (MSA-C) are distinguished. Sporadic adult onset ataxias of unknown aetiology (SAOA) denote all non-hereditary degenerative adult onset ataxias distinct from MSA-C, but early differential diagnosis is often difficult. Using voxel-based morphometry (VBM) we found previously cerebellar grey and white matter loss (GML/WML) in MSA and SAOA, whereas brainstem (WML), basal ganglia and several cortical regions (GML) were only affected in MSA. To further investigate white matter pathology (WMP) in MSA and SAOA we used diffusion-tensor-imaging (DTI) and correlated changes with clinical data.

We compared 14 MSA- (m/f: 9/5, age 61.4±5.2 years (y), MSA-C/MSA-P: 10/4, disease duration (dd) 3.6±1.8y) and 18 IDCA-patients (m/f: 8/10, age 51.4±11.9y, dd 8.4±5.5y) with age- and sex-matched healthy controls (MSA controls: m/f: 9/5, age 58.7±5.1y; SAOA controls: m/f: 8/9, age 52.5±8.6y). All subjects underwent neurological and neuropsychological examinations. Diffusion weighted images were obtained using a 3T MRI scanner with 60 gradient directions and a novel registration and analysis approach (Tract Based Spatial Statistics) was applied. FSL was used for preprocessing and statistical analysis of DTI data (2-sample t tests, p<0.05, FWE-corrected).

In MSA we found significant degradation of fractional anisotropy (DFA) in infratentorial fibre tracts affecting middle CPs and pontine crossing tract. Further supratentorial DFA was found in the left corticospinal tract. In SAOA DFA was depicted in superior CPs, right inferior CP and also in the corpus callosum (CC).

DTI analyses demonstrated distinct WMP in MSA, affecting only projection fibre tracts, whereas commissural (CFTs) or association fibre tracts (AFTs) were spared. Instead, we found DFA in SAOA not only in CPs but also in CC, the largest CFT. Neuropsychological data analyses and correlation studies of brain morphometric and clinical data are currently underway. The pattern of cortical GML (VBM) with preserved CFTs (DTI) in MSA is distinct from the one found in SAOA without cortical GML but affected CFT. Detection of disease-specific morphometric pattern provides deeper insights in neuropathological differences and may improve the accuracy of clinical diagnosis.