Our data show that we can validly quantify lower extremity vibration sensation and strength in individuals with MS using clinically accessible tools and that these tools can detect differences among MS subtypes (i.e., RRMS, SPMS, and PPMS) and healthy controls. Vibration sensation and strength were significantly correlated to MS subtype and we found significant differences that were dependent on disease duration. Overall, all MS subtypes had significantly worse vibration sensation and strength when compared to matched controls. As expected, the RRMS group had better sensation, were stronger, walked more quickly than the progressive groups, and had the lowest EDSS scores. More importantly, our quantitative sensorimotor measures significantly correlated with global disability measures (i.e. EDSS, FSS, and T25FW) and remarkably these quantitative measures were able to detect abnormalities in MS subjects with documented normal sensory and pyramidal FSS.
Since MS is a heterogeneous and unpredictable disease with very limited medical and neurorehabilitation interventions, many investigators have emphasized the need for more sensitive and responsive functional outcome measures [6
]. An international task force was formed by the National MS Society to address this need which led to the development of the Multiple Sclerosis Functional Composite (MSFC) [25
]. The MSFC is a composite measure that evaluates cognition, arm function, and walking and has been shown to have excellent intra-rater and inter-rater reliability [27
]. As a result, the MSFC is now widely used and has been incorporated into many clinical trials as an outcome measure [21
]. In this study, we used quantitative tools that measure specific sensory and motor impairments that correlate with functional tract specific MRI pathology in MS [15
]. These quantitative measures might be more sensitive in evaluating specific and subtle impairments compared to the commonly used rating scales. They offer additional advantages in that they are precise, objective, , and remain more cost-effective and transportable than tools such as an isokinetic device.
Up to this point, it has been very difficult to quantify subtle vibration sensation loss, which often occurs early in MS. Neurological exams which include tuning fork vibration testing is variable and often subjective [29
]. The Vibratron II measures vibration sensation in a more objective fashion, and it uses a constant frequency, an adjustable magnitude, and a systematic data collection paradigm [8
]. Our data show differences among the MS subtypes along with a significant correlation between vibration sensation and the EDSS in the RRMS group. By contrast, this was not seen within the progressive groups. Vibration sensation dysfunction in RRMS may be a marker for early disease progression and suggests that this is less appreciated in more advanced, progressive disease. Additionally, irrespective of disease subtype, we found that almost 30% of MS subjects who had a normal
sensory FSS actually had abnormal quantitative vibration sensation (i.e., at least 2.5 standard deviations outside of age-matched controls). We suggest that the Vibratron II has the potential to be a useful clinical outcome measure in MS.
Similar to vibration sensation, traditional strength testing has been reliant on insensitive rating scales and subjective clinical exams. We used a hand-held dynamometer because it is faster to use and clinically more accessible than other devices available [8
]. In our cohort, the majority of individuals with RRMS and all individuals with SPMS and PPMS were found to have significantly weaker ankle dorsiflexion and hip flexion than matched controls. We also found that the early PPMS group had significantly stronger hip flexion compared to the late PPMS group. This difference corresponds with previous natural history studies as PPMS typically presents with a progressive myelopathy [30
]. Currently, there are few outcome measures that detect subtle clinical abnormalities in individuals with progressive MS making it difficult to evaluate possible treatments [32
]. Irrespective of disease subtype, we found that strength was detected as abnormal in 32% and 4% of MS subjects who had a normal pyramidal FSS (for ankle dorsiflexion and hip flexion, respectively). These findings suggest that quantitative measures might detect even small deficits that are missed by rating scales and that ankle dorsiflexion weakness is an early deficit that is often overlooked. We suggest that quantitative strength testing could be an effective clinical outcome measure, especially for progressive MS.
Walking is an important functional goal for individuals with MS. Gait abnormalities can often present early in MS without obvious functional impairment [33
]. Despite this observation, very little research has focused on the details of what may be contributing to these gait problems. Perhaps this is because in MS the clinical gold standard has been to use rating scales or timed walk tests to evaluate global problems with walking [2
]. However, our data show that we can measure lower extremity vibration sensation and strength in a more quantitative fashion than what has been done in the past and that these functions are deficient relative to a control cohort. Previous studies have shown that poor sensation and poor strength result in an increased number of falls and slower walking speeds in individuals with MS [35
]. As such, our results provide a basis for future studies to evaluate walking in relation to quantitative sensory and motor impairments. We propose that the tools in this study have the potential to assist in predicting who might have future ambulation problems and therefore allow us to intervene earlier with strategic rehabilitation approaches and MS drug therapies.
There are several limitations to our study. We performed a cross-sectional study which does not allow for definitive conclusions about the sensitivity and validity of the quantitative devices used over time. To address this we plan to use baseline values from this study in a prospective, longitudinal study. Our measure of vibration sensation is valid and more objective than the tuning fork; however, the Vibratron device can only be used for testing at the great toe and index finger. Ideally, one would like to evaluate vibration sensation at multiple points. Our measure of strength is valid and objective [8
]; however, we only tested two muscle actions. We chose ankle dorsiflexion and hip flexion strength because clinically these are common sites of weakness in MS. Also, this accounts for proximal and distal impairments, both of which are important in walking [8
]. Lastly, quantitative strength testing methods requires examiners to be trained for proper testing technique and assumes the patient is participating with their full effort. To control for this we had one experienced tester (K.M.Z.) train and monitor all testers using the same testing technique.
Abnormalities of sensation and strength are common deficits that affect many people who suffer from MS. Our data demonstrate that we can quantify abnormalities in vibration sensation and strength in MS and distinguish differences among MS subtypes and controls using clinically accessible tools. More broadly, this study shows that sensory and motor impairments can be measured using the Vibratron device and a hand-held dynamometer. We suggest that these tools could be used to evaluate impairments in the upper extremity as well as the lower extremity. Our impairment data strongly correlated with the commonly used EDSS and T25FW, and detected abnormalities in up to 32% of MS subjects with “normal” sensory and pyramidal FSS. These observations support the notion that the Vibratron device and hand-held dynamometer have the potential to be used as outcome measures in future MS clinical trials of neurorehabilitative and neuroreparative interventions. Use of these tools in a longitudinal study would allow for the quantification of early deficits and improve prediction of future changes in functional measures such as ambulation.