Combining Magnetization Transfer Ratio MRI and Quantitative Measures of Walking Improves the Identification of Fallers in MS

Abstract

Multiple sclerosis (MS) impacts balance and walking function, resulting in accidental falls. History of falls and clinical assessment are commonly used for fall prediction, yet these measures have limited predictive validity. Falls are multifactorial; consideration of disease-specific pathology may be critical for improving fall prediction in MS. The objective of this study was to examine the predictive value of clinical measures (i.e., walking, strength, sensation) and corticospinal tract (CST) MRI measures, both discretely and combined, to fall status in MS. Twenty-nine individuals with relapsing-remitting MS (mean ± SD age: 48.7 ± 11.5 years; 17 females; Expanded Disability Status Scale (EDSS): 4.0 (range 1–6.5); symptom duration: 11.9 ± 8.7 years; 14 fallers) participated in a 3T brain MRI including diffusion tensor imaging and magnetization transfer ratio (MTR) and clinical tests of walking, strength, sensation and falls history. Clinical measures of walking were significantly associated with CST fractional anisotropy and MTR. A model including CST MTR, walk velocity and vibration sensation explained >31% of the variance in fall status (R2 = 0.3181) and accurately distinguished 73.8% fallers, which was superior to stand-alone models that included only MRI or clinical measures. This study advances the field by combining clinical and MRI measures to improve fall prediction accuracy in MS.

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance

“…33 Surveys show that mobility impairment is a top symptom of importance to people with MS. [16][17][18][19] Greater walking impairment, and more severe overall impairment, is experienced in the progressive compared with the relapsing remitting phase, with indications of greater impairments in primary compared with secondary progressive MS. 33 As mobility impairment increases, functional limitations can lead to safety concerns with increased likelihood of falls, and greater barriers to participation in rehabilitation. 34 Mobility studies investigating the biological mechanisms of impairment and recovery at molecular, cellular, and synaptic levels are encouraging; some focus exclusively on progressive MS. 35 These provide preliminary evidence of the potential impact of exercise on neuroprotection and regeneration in animal models 36 and humans. 10,37 While these mechanistic studies vary in methodological quality, these inter-disciplinary collaborations provide a foundation for future work to inform the design of rehabilitation interventions.…”

“…33 Surveys show that mobility impairment is a top symptom of importance to people with MS. 16–19 Greater walking impairment, and more severe overall impairment, is experienced in the progressive compared with the relapsing remitting phase, with indications of greater impairments in primary compared with secondary progressive MS. 33 As mobility impairment increases, functional limitations can lead to safety concerns with increased likelihood of falls, and greater barriers to participation in rehabilitation. 34…”

“…imaging measures of brain volume or white matter tracts) into rehabilitation trials. Although biomarkers have improved the understanding of how treatments may work and supported development of algorithms to inform clinical decision-making in MS, 34,39 there is very little evidence validating biomarkers in progressive MS, highlighting an important gap in our knowledge.…”

Cerebellar volume measures may differentiate multiple sclerosis fallers from non-fallers

“…Our lab has demonstrated associations between neuroimaging metrics and fall risk [9], including the utility of combining clinical measures with quantitative imaging metrics to improve identi cation of fallers in PwMS [10][11]. Given the complexity and diversity of factors associated with fall risk, it is likely that several brain regions are contributing to fall risk as well.…”

Associations between myelin water imaging and measures of fall risk and functional mobility in multiple sclerosis

“…Specifically, DTI studies have shown lower fractional anisotropy in the corticospinal tract (CST), superior cerebellar peduncles (SCP), and corpus callosum (CC) relating to worse walking performance in PwMS 6–8 . Similarly, MTR studies have demonstrated correlations between lower MTR values and worse motor function 6,9 in PwMS. Yet, DTI and MTR imaging exhibit limited specificity to the interpretation of results 10 .…”