Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis

Abstract

IMPORTANCE Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians. OBJECTIVE To determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019. EXPOSURES MWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS. MAIN OUTCOMES AND MEASURES The association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest-the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum-were selected a priori according to their known involvement in MS-related cognitive impairment. RESULTS For the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Fortyeight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test

GABABR agonist baclofen promotes central nervous system remyelination

“…Interestingly, it has been highlighted that intrathecal Bac administration in MS patients is linked to improved cognitive performance (Farrel et al, 2021). Notably, higher cognitive performance in patients with MS has been associated to quantitative improvements in myelin water imaging (Abel et al, 2020). Here, we show that Bac administration stimulates myelin protein synthesis and remyelination ex vivo and in vivo .…”

Modern Technology in Multi-Shell Diffusion MRI Reveals Diffuse White Matter Changes in Young Adults With Relapsing-Remitting Multiple Sclerosis

“…The role of myelin damage in MS-related cognitive dysfunction has been demonstrated by other imaging techniques, like myelin water imaging ( Abel et al, 2020 ), but there’s increasing evidence that gray matter damage plays a major role. Studies using DTI and conventional MRI measures showed that gray matter atrophy of various cortical and subcortical regions was associated with a reduction in PASAT performance ( Uher et al, 2014 ; Riccitelli et al, 2019 ).…”

Clinical Applications of Myelin Plasticity for Remyelinating Therapies in Multiple Sclerosis

“…41,42 Sequences such as myelin water imaging (MWI), magnetization transfer imaging (MT), and direct ultrashort echo time (UTE) are also potential modalities that are theorized to capture myelin more specifically on the basis of their interaction with its unique biophysical properties. 44,45,46 However, empirical validation of these techniques, such as through correlating signal changes with demyelinating lesions in MS patients in whom there is extensive axonal damage, edema, inflammatory infiltration, and gliocytosis, demonstrate only partial histological associations and are profoundly subject to the same confounders as DTI. 43,45,46 Positron emission tomography (PET) utilizes radiotracers, such as stilbene derivatives, that can be targeted toward myelin with molecular specificity, and has been deployed to track disease progression in MS, but PET technology is costly and not widely available.…”

“…Abnormalities of MWI in MS patients and decreased myelination in mouse models correlate with cognitive deficits, and there is preliminary evidence that cognitive exercises and rehabilitation alleviate these symptoms in a clinical setting. 44,56,[63][64][65][66][67] However, as with physical rehabilitation and noninvasive neuromodulation approaches, the development of neuroimaging biomarkers of remyelination and their application in prospective trials as a primary outcome will be critical in determining the degree to which these clinical benefits are mediated through myelin repair. Moreover, future studies should be designed with longer follow-up times to demonstrate more robust and long-term effects prior to the consideration of clinical trials.…”