Quantitative measures detect sensory and motor impairments in multiple sclerosis

Abstract

Background

Sensory and motor dysfunction in multiple sclerosis (MS) is often assessed with rating scales which rely heavily on clinical judgment. Quantitative devices may be more precise than rating scales.

Objective

To quantify lower extremity sensorimotor measures in individuals with MS, evaluate the extent to which they can detect functional systems impairments, and determine their relationship to global disability measures.

Methods

We tested 145 MS subjects and 58 controls. Vibration thresholds were quantified using a Vibratron-II device. Strength was quantified by a hand-held dynamometer. We also recorded Expanded Disability Status Scale (EDSS) and Timed 25-Foot Walk (T25FW). t-tests and Wilcoxon-rank sum were used to compare group data. Spearman correlations were used to assess relationships between each measure. We also used a step-wise linear regression model to determine how much the quantitative measures explain the variance in the respective functional systems scores (FSS).

Results

EDSS scores ranged from 0–7.5, mean disease duration was 10.4 ± 9.6 years, and 66% were female. In relapsing-remitting MS, but not progressive MS, poorer vibration sensation correlated with a worse EDSS score, whereas progressive groups' ankle/hip strength changed significantly with EDSS progression. Interestingly, not only did sensorimotor measures significantly correlate with global disability measures (i.e., EDSS), but they had improved sensitivity, as they detected impairments in up to 32% of MS subjects with normal sensory and pyramidal FSS.

Conclusions

Sensory and motor deficits in MS can be quantified using clinically accessible tools and distinguish differences among MS subtypes. We show that quantitative sensorimotor measures are more sensitive than FSS from the EDSS. These tools have the potential to be used as clinical outcome measures in practice and for future MS clinical trials of neurorehabilitative and neuroreparative interventions.

Introduction

Multiple sclerosis (MS) is a complex and clinically heterogeneous disease of the central nervous system that often results in marked disability. The lesions that occur in MS can cause many neurological deficits, depending on their location and extent [1]. Common deficits include impairments of sensation, pyramidal tract dysfunction, and gait abnormalities. Evaluating MS disability has consistently relied on rating scales such as the Expanded Disability Status Scale (EDSS) [2], the Scripps Neurologic Rating Scale [3], the 12-item MS Walking Scale [4], and the Ambulation index [5]. These rating scales provide a good overall assessment of an individual's functional status; however, it is well-known that they are insensitive to subtle abnormalities and provide limited information about which impairments may be specifically contributing to an individual's loss of function [1], [6], [7]. Clinical rehabilitation studies could gain both statistical power and meaning from the use of more specific outcome measures that are sensitive to subtle neurological impairments [6], [7].

Quantitative functional testing devices such as the Vibratron II (for vibration sensation) and the hand-held dynamometer (for strength) have been used to evaluate impairments in sensation and strength for various neurological conditions including adrenomyeloneuropathy, cerebral palsy, traumatic brain injury, and peripheral neuropathy [8], [9], [10], [11], [12], [13], [14]. These devices are clinically accessible and have the potential for systematically quantifying specific impairments in MS; however, this has not been investigated. Using the same devices in a previous study, we found that impairments in vibration sensation and strength were significantly correlated with column-specific abnormalities in the spinal cord of MS subjects [15], [16]. What remains unclear is whether these tools can reliably differentiate MS impairments from controls, distinguish impairments between MS subtypes, and whether they are as sensitive or more sensitive than categorical rating scales in detecting impairments.

We hypothesized that the Vibratron II and the hand-held dynamometer are able to detect abnormalities of sensory and motor impairments in a heterogeneous group of MS patients and that they are more precise than their respective sensory and pyramidal functional system scores (FSS) of the EDSS (i.e., a global measures of disability in MS). The primary objectives of this study were to: 1) obtain baseline reference values for lower extremity quantitative sensorimotor measures in MS subjects, 2) examine whether these quantitative measures detect differences between MS subjects and matched controls, 3) compare these measures between MS subtypes, 4) evaluate the extent to which these measures correlate with global disability measures such as the EDSS and 5) evaluate their sensitivity compared to their respective EDSS FSS. This study provides the framework to begin validating the use and reliability of the Vibratron II and hand-held dynamometer as relevant MS clinical biomarkers of sensory and motor impairment.