Romascano D, Meskaldji DE, Bonnier G, Simioni S, Rotzinger D, Lin YC, Menegaz G, Roche A, Schluep M, Pasquier RD, Richiardi J, Van De Ville D, Daducci A, Sumpf T, Fraham J, Thiran JP, Krueger G, Granziera C. Multicontrast connectometry: A new tool to assess cerebellum alterations in early relapsing-remitting multiple sclerosis. Hum Brain Mapp. 2014. doi: 10.1002/hbm.22698. [Epub ahead of print]
Background: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. Methods: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores.
Results: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, p= 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage.
Conclusion: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage.
Some odd assumptions in the abstract aside ("cerebellar pathology occurs in late multiple sclerosis..."), the findings of this study performed in MSers are line with work by our group using post mortem brain of people who had died with MS (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277890/).
Using MRI changes are detectable in MS brain tissue outside of lesions, and the substrate of these changes may be early axonal "stress" (e.g. swelling due to changes in the phosphorylation status of neurofilaments). These "non-lesional" pathological changes in MS remain poorly explained though there is some evidence they occur as a result of lesions elsewhere in the nervous system (retro- or anterograde axonal degeneration).