Multiple sclerosis (MS) is a chronic demyelinating, inflammatory, and neurodegenerative disease of the central nervous system (CNS) that generally affects the young and working-age population. (AJ Thompson et al., 2018) The disease is typically characterized by early episodes of acute neurological worsening (relapses) with either full or only partial recovery. (AJ Thompson et al., 2018) After variable amount of disease duration (an average of 15–20 years), most people with MS (pwMS) transition into a progressive stage of the disease with gradual but constant accrual of neurological disability. (AJ Thompson et al., 2018) In a smaller and under-researched group of pwMS, the disease has a highly active, rapidly worsening course, often described as “severe MS”. (Iacobaeus et al., 2020)

The widely used Expanded Disability Status Scale (EDSS) score emphasizes mobility restriction and lacks considerations for neurological impairments such as visual problems, manual dexterity, sexual dysfunction, fatigue, depression, and/or cognitive deficiencies except in lower scores (i.e., EDSS ≤ 3.5). (Twork et al., 2010) In severely disabled pwMS, these additional symptoms and limitations influence quality of life (QoL) and the well-being of caregivers. (Borreani et al., 2014), (Freeman et al., 2020) Only a few studies have investigated pwMS with severe MS with EDSS > 8.0, who are essentially restricted to bed or chair (Edmonds et al., 2007), (Higginson et al., 2006). People with the severe MS disease phenotype are generally excluded from participation in disease-modifying treatment (DMT) trials.

The grouping of severely disabled pwMS in categories based on mobility (use of uni/bilateral walking support, wheelchair use, or restricted to bed) merges together phenotypically different pwMS. For example, wheelchair-restricted pwMS can have different QoL based on the presence of severe cognitive impairment, upper extremity limitations, dysphagia/dysarthria or bladder and bowel incontinence. Moreover, their “equal” disability scores will potentially produce discrepant results when correlated with their extent of neurodegenerative and demyelinating pathology. This “clinico-radiological” paradox is well known in the literature and represents a state where the phenotypical disability is not well represented by the MRI features of the pwMS. (Chard and Trip, 2017) In some instances, the pwMS could have substantial physical/cognitive disability with no appreciable MRI changes and some pwMS could be appear neurologically well despite evidence of considerable MRI pathology. The use of more specific disability scores that reflect disparate modes of MS disability could aid in reducing the apparent clinico-radiological discrepancy.

Based on this background, we investigated five different MS disability assessment methods/scores in a group of severely disabled pwMS. Moreover, we aimed at utilizing these measures to better understand the clinico-radiological relationship in the severe MS population. This study leverages a group of severely disabled pwMS from The Boston Home (TBH), a specialized MS care facility located in Massachusetts, United States. We hypothesized that disability measures that provide more comprehensive and granular overview of the MS limitations better reflect the underlying brain pathology as assessed by MRI.