Testud B, Delacour C, El Ahmadi AA, Brun G, Girard N, Duhamel G, Heesen C, Häußler V, Thaler C, Has Silemek AC, Stellmann JP

Background: Extend and dynamic of neurodegeneration in progressive Multiple Sclerosis (MS) might be reflected by global and regional brain perfusion, an outcome at the intercept between structure and function. Here, we provide a first insight in the evolution of brain perfusion and its association with disability in primary progressive MS (PPMS) over several years. Methods: 77 persons with PPMS were followed over up to 5 years. Visits included a 3T MRI with pulsed Arterial spin labelling (ASL) perfusion, the Timed-25-Foot-Walk, 9-Hole-Peg-Test (NHPT), Symbol-Digit-Modalities-Test (SDMT) and Expanded Disability Status Scale (EDSS). We extracted regional cerebral blood flow surrogates and compared them to 11 controls. Analyses focused in cortical and deep gray matter, the change over time and associations with disability on regional and global level. Results: Baseline brain perfusion of patients and controls was comparable for the cortex (p=0.716) and deep grey matter (p=0.095). EDSS disability increased mildly (p=0.023) while brain perfusion decreased during follow up (p<0.001) and with disease duration (p=0.009). Lower global perfusion correlated with higher disability as indicated by EDSS, NHPT and Timed-25-Foot-Walk (p<0.001). The motor task NHPT showed associations with twenty gray matter regions. In contrast, better SDMT performance correlated with lower perfusion (p<0.001) in seven predominantly frontal regions indicating a functional maladaptation. Conclusion: Decreasing perfusion indicates a putative association with MS disease mechanisms such as neurodegeneration, reduced metabolism, and loss of resilience. A low alteration rate limits its use in clinical practice, but regional association patterns might provide a snapshot of adaptive and maladaptive functional reorganization

Eur J Neurol. 2022 Jun;29(6):1741-1752.

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