Longitudinal Clinical and Brain Mri Changes in Multiple System Atrophy

Objective: To assess clinical, cognitive, and neuroimaging brain changes in patients with multiple system atrophy-parkinsonian type (MSA-p). Background: With the emergence of potential disease-modifying agents for neurodegenerative diseases, the development of new biomarkers is becoming an urgent issue in order to improve diagnostic accuracy and prognosis definition, and to monitor the efficacy of the therapeutic approaches in these conditions. Methods: We enrolled 25 MSA-p patients and 21 matched healthy controls. Patients underwent clinical and neuropsychological evaluations and MRI scan at baseline and after a mean follow-up (FU) of 1.1 years. At baseline, MRI was obtained from healthy controls. Changes in cortical thickness and diffusion tensor (DT) MRI metrics of white matter (WM) tracts were assessed in MSA-p patients. Results: During follow up, MSAp patients showed a worsening of motor impairment, cognitive deficits and behavioural changes. At baseline, MRI study did not detect significant cortical and WM abnormalities in MSA-p patients compared with controls. After 1 year, MSA-p patients showed only a subtle, focal thinning of the fronto-temporal cortices. Conversely, they showed significant, severe WM changes involving the corpus callosum, and frontotemporal and frontoparietal connections bilaterally (anterior>posterior). No longitudinal changes were observed in the infratentorial regions. In MSA-p, the progressive involvement of corpus callosum, external capsule, and long-range associative WM pathways bilaterally was associated with the worsening of cognitive deficits and behavioral changes. Conclusions: In MSA-p patients, the progression of WM microstructural damage is prominent compared to cortical damage and may explain the worsening of cognitive and behavioural symptoms. DT MRI has the potential to offer promising biomarkers for monitoring MSA-p and predicting the clinical evolution. Disclosure: Dr. Caso has nothing to disclose. Dr. Agosta has received personal compensation for activities with Biogen Idec and EXCEMED– Excellence in Medical Education. Dr. Nikolic has nothing to disclose. Dr. Jecmenica has nothing to disclose. Dr. Petrovic has nothing to disclose. Dr. Stankovic has nothing to disclose. Dr. Kostic has received personal compensation for activities with Novartis, Boehringer Ingelheim Pharmaceuticals, Merck & Co., Inc., Lundbeck Research USA, Inc., GlaxoSmithKline, Hoffman-La Roche, Alkaloid, and AbbVie as a speaker. Dr. Filippi has received personal compensation for activities for consulting services and/or speaking activities from Biogen Idec, Excemed, Novartis, and Teva Pharmaceutical Industries.