Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function

Abstract

Background and purpose Extent 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 into the evolution of brain perfusion and its association with disability in primary progressive MS (PPMS) over several years. Methods Seventy‐seven persons with PPMS were followed over up to 5 years. Visits included a 3‐T magnetic resonance imaging with pulsed arterial spin labelling 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 on cortical and deep grey matter, the change over time, and associations with disability on the regional and global levels. 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), whereas 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 20 grey matter regions. In contrast, better SDMT performance correlated with lower perfusion (p < 0.001) in seven predominantly frontal regions, indicating a functional maladaptation. Conclusions 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.

Characteristics of cerebral blood flow in an Eastern sample of multiple sclerosis patients: A potential quantitative imaging marker associated with disease severity

“…3) Relative CBF images were calculated by general kinetic modelling using the BASIL FSL toolbox ( 16 ). 4) Absolute CBF was calibrated by surrogate M 0 images calculated from the averaged control images ( 17 ).…”

Symbol Digit Modalities Test in progressive multiple sclerosis

“…It was also demonstrated that hypoperfusion in the superior medial frontal cortex and subcortical grey matter of SPMS subjects correlates the most closely with SDMT among the utilised batteries, although the results were ambiguous [46]. In contrast, a prospective observational cohort study (PPMS n = 77) demonstrated that lower perfusion in several brain regions (including left pars triangularis, left lateral orbitofrontal, right medial orbitofrontal, right pars opercularis, right rostral anterior cingulate, right amygdala, and right putamen) correlated with better SDMT score, which was suggested to be a result of functional maladaptation [47].…”

“…Interesting findings came from research based on perfusion MRI [46,47]. Assessment of perfusion MRI in 45 SPMS patients revealed that among the applied neuropsychological tools, SDMT showed the best correlation with cerebral perfusion.…”

Translation, Cross-Cultural Adaptation, and Feasibility of the NHPT-E of Manual Dexterity for the Spanish Population

“…Subsequently, Mathiowetz et al, in 1985 [ 14 ], detailed the instructions for its administration [ 14 ], analyzed its psychometric properties of reliability and validity, and presented normative data [ 14 , 15 ]. The NHPT has been widely used in different populations, mostly with neurological pathologies such as Parkinson’s disease [ 16 ], multiple sclerosis [ 17 ], and stroke [ 18 ], among others. Validation studies carried out with neurological disease show that this tool presents optimal psychometric properties, with high reliability indices in terms of an interclass correlation coefficient (ICC) between 0.95 and 0.99 [ 15 , 19 , 20 ] and validity analyses correlating NHPT with hand grip and finger pinch.…”