Upper Cervical Cord Atrophy Predicts Disability Through Motor Clinical Impairment in Multiple Sclerosis Patients
Matteo Albergoni1, Chiara Dallari1, Paola Valsasina1, Monica Margoni2, Martina Rubin3, Massimo Filippi4, Maria Rocca3
1Neuroimaging Research Unit, Division of Neuroscience, 2Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; and Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, 3Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, 4Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University
Objective:
To understand if the association between upper cervical cord atrophy and disability is direct or indirectly mediated by motor clinical impairment in multiple sclerosis (MS) patients.
Background:
MS is one of the most common causes of neurological disability in young adults and it is characterized by several motor symptoms, among which, impaired walking capacity and manual dexterity. In MS, structural damage of the cervical spinal cord is frequent and already present from early disease stages. Mean upper cervical cord area (MUCCA) measurement can be used to quantify cervical cord atrophy and it seem to be directly associated with disability, walking capacity and manual dexterity in MS.
Design/Methods:
In this cross-sectional study, expanded disability status scale (EDSS), timed 25-foot walk (T25FW), six-minute walk test (6MWT), timed up and go (TUG) test, finger tapping (FT), nine-hole peg test (9HPT) and MUCCA measure (derived from 3D T1-weigthed brain images) were collected for 60 MS patients and 36 healthy controls (HC). In MS, the associations between MUCCA and clinical variables were explored. Then focusing on the relation between MUCCA and EDSS, we performed a mediation analysis to understand the potential role of clinical impairment as mediator.
Results:
In MS, lower MUCCA was associated with higher EDSS (R=-0.47, p<0.001) and lower values of inverse TUG (R=0.41, p=0.002), inverse T25FW (R=0.38, p=0.003), 6MWT (R=0.38, p=0.004) and FT (R=0.39, p=0.003). Within the mediation model, there was no direct effect of MUCCA on EDSS (β=-0.02, 95%CI [-0.05;0.01]), but there was a significant total indirect effect acting through T25FW, 6MWT, TUG and FT (β=-0.06, 95%CI [-0.10;-0.03]). Singularly, none of the clinical impairment seems to act as mediator.
Conclusions:
In MS, in accordance with the ICF system, upper cervical cord atrophy predicts disability, but this relation is indirectly mediated by the overall impact of impairment in walking capacity, balance and manual dexterity domains.