Cervical cord atrophy provides a relevant and useful marker for the characterization of clinical heterogeneity of patients with MS. The stability of this measure among different centers supports its use as potential outcome measure to monitor disease progression in multicenter trials.

We investigated the diagnostic accuracy of brainstem MRI measurements in patients with different progressive supranuclear palsy (PSP) syndromes and Parkinson's disease (PD). Using 3D T1-weighted images, midbrain, and pons areas, as well as superior (SCP) and middle cerebellar peduncle (MCP) widths were measured in 10 patients with Richardson's syndrome (PSP-RS), 10 patients with PSP-parkinsonism (PSP-P), 25 patients with PD, and 24 healthy controls. The ratio between pons and midbrain areas (pons/midbrain), that between MCP and SCP widths (MCP/SCP), and the MR parkinsonism index ([pons/midbrain]*[MCP/SCP]) were calculated. The pons/midbrain and the MR parkinsonism index allowed to differentiate PSP-RS from PD with high sensitivity (90%, 100%), specificity (96%, 92%), and accuracy (94%, 97%). Only the pons/midbrain was found to distinguish PSP-P from PD, but with a lower diagnostic accuracy (sensitivity = 60%, specificity = 96%, accuracy = 86%). Compared to PSP-RS, PSP-P experience a relatively less severe involvement of infratentorial brain. The pons/midbrain looks as a promising measure in the differentiation of individual PSP-P from PD patients.

Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.

Voxelwise assessment of DT MR index abnormalities is a rewarding strategy for understanding the heterogeneity of clinical MS phenotypes.

Both trans-synaptic degeneration secondary to optic nerve damage and Wallerian degeneration due to local T2 lesions contribute to OR damage in MS.

The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS.

Voxel-based assessment of cervical cord damage is feasible and may contribute to a better characterisation of the clinical heterogeneity of MS patients.

After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis.