Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients.

Multiple sclerosis is a neuroinflammatory disease of the CNS that is associated with significant irreversible neuro-axonal loss, leading to permanent disability. There is thus an urgent need for in vivo markers of axonal loss for use in patient monitoring or as end-points for trials of neuroprotective agents. Advanced diffusion MRI can provide markers of diffuse loss of axonal fibre density or atrophy within specific white matter pathways. These markers can be interrogated in specific white matter tracts that underpin important functional domains such as sensorimotor function. This study aimed to evaluate advanced diffusion MRI markers of axonal loss within the major sensorimotor tracts of the brain, and to correlate the degree of axonal loss in these tracts to precise kinematic measures of hand and foot motor control and gait in minimally disabled people with multiple sclerosis. Twenty-eight patients (Expanded Disability Status Scale < 4, and Kurtzke Functional System Scores for pyramidal and cerebellar function ≤ 2) and 18 healthy subjects underwent ultra-high field 7 Tesla diffusion MRI for calculation of fibre-specific measures of axonal loss (fibre density, reflecting diffuse axonal loss and fibre cross-section reflecting tract atrophy) within three tracts: cortico-spinal tract, interhemispheric sensorimotor tract and cerebello-thalamic tracts. A visually guided force-matching task involving either the hand or foot was used to assess visuomotor control, and three-dimensional marker-based video tracking was used to assess gait. Fibre-specific axonal markers for each tract were compared between groups and correlated with visuomotor task performance (force error and lag) and gait parameters (stance, stride length, step width, single and double support) in patients. Patients displayed significant regional loss of fibre cross-section with minimal loss of fibre density in all tracts of interest compared to healthy subjects (family-wise error corrected p-value < 0.05), despite relatively few focal lesions within these tracts. In patients, reduced axonal fibre density and cross-section within the corticospinal tracts and interhemispheric sensorimotor tracts were associated with larger force tracking error and gait impairments (shorter stance, smaller step width and longer double support) (family-wise error corrected p-value < 0.05). In conclusion, significant gait and motor control impairments can be detected in minimally disabled people with multiple sclerosis that correlated with axonal loss in major sensorimotor pathways of the brain. Given that axonal loss is irreversible, the combined use of advanced imaging and kinematic markers could be used to identify patients at risk of more severe motor impairments as they emerge for more aggressive therapeutic interventions.

Functional correlates of motor control impairments in multiple sclerosis: A 7 Tesla task functional MRI study.

Upper and lower limb impairments are common in people with multiple sclerosis (pwMS), yet difficult to clinically identify in early stages of disease progression. Tasks involving complex motor control can potentially reveal more subtle deficits in early stages, and can be performed during functional MRI (fMRI) acquisition, to investigate underlying neural mechanisms, providing markers for early motor progression. We investigated brain activation during visually guided force matching of hand or foot in 28 minimally disabled pwMS (Expanded Disability Status Scale (EDSS) < 4 and pyramidal and cerebellar Kurtzke Functional Systems Scores ≤ 2) and 17 healthy controls (HC) using ultra-high field 7-Tesla fMRI, allowing us to visualise sensorimotor network activity in high detail. Task activations and performance (tracking lag and error) were compared between groups, and correlations were performed. PwMS showed delayed (+124 s, p = .002) and more erroneous (+0.15 N, p = .001) lower limb tracking, together with lower cerebellar, occipital and superior parietal cortical activation compared to HC. Lower activity within these regions correlated with worse EDSS (p = .034), lower force error (p = .006) and higher lesion load (p < .05). Despite no differences in upper limb task performance, pwMS displayed lower inferior occipital cortical activation. These results demonstrate that ultra-high field fMRI during complex hand and foot tracking can identify subtle impairments in lower limb movements and upper and lower limb brain activity, and differentiates upper and lower limb impairments in minimally disabled pwMS.

What speech can tell us: A systematic review of dysarthria characteristics in Multiple Sclerosis.

IMPORTANCE: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression. OBSERVATIONS: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis. CONCLUSION AND RELEVANCE: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials.

Technologies for Advanced Gait and Balance Assessments in People with Multiple Sclerosis.

Subtle gait and balance dysfunction is a precursor to loss of mobility in multiple sclerosis (MS). Biomechanical assessments using advanced gait and balance analysis technologies can identify these subtle changes and could be used to predict mobility loss early in the disease. This update critically evaluates advanced gait and balance analysis technologies and their applicability to identifying early lower limb dysfunction in people with MS. Non-wearable (motion capture systems, force platforms, and sensor-embedded walkways) and wearable (pressure and inertial sensors) biomechanical analysis systems have been developed to provide quantitative gait and balance assessments. Non-wearable systems are highly accurate, reliable and provide detailed outcomes, but require cumbersome and expensive equipment. Wearable systems provide less detail but can be used in community settings and can provide real-time feedback to patients and clinicians. Biomechanical analysis using advanced gait and balance analysis technologies can identify changes in gait and balance in early MS and consequently have the potential to significantly improve monitoring of mobility changes in MS.

Sagittal plane lumbar loading when navigating an obstacle and carrying a load.

The current study quantified lumbar loading while carrying an anterior load mass and navigating an obstacle. Eight healthy male participants walked down a walkway and crossed an obstacle under three randomised LOAD conditions; empty-box (2 KG), five kilogram (5 KG) and ten kilogram (10 KG). Each walk was assessed at two events: left foot mid-stance (LMS) and right toe-crossing (TC) to characterise any changes from approach to crossing. Measures of interest included: trunk pitch, L4/L5 joint moment, compression, joint anterior-posterior shear and erector spinae activation. Findings demonstrate that obstacle crossing extended posture by 50, 41, 44%, respectively for each carried load magnitude. Further, these results indicate that shear rather than compressive loading may be an important consideration during crossing due to increase by 8, 9, 22% from LMS to TC for each load magnitude tested. These results provide insight into sagittal lumbar loading when navigating an obstacle while carrying a load. Practitioner Summary: The risk of carrying while navigating obstacles on the lumbar spine is not completely understood. The forces at the lumbar spine while simultaneously carrying and obstacle crossing were analysed. Data indicate that carrying and obstacle crossing influence lumbar shear loads, thereby moderately increasing the relative risk at lumbar spine.

Organisation of the motor cortex differs between people with and without knee osteoarthritis.

INTRODUCTION: The aim of this study was to investigate possible differences in the organisation of the motor cortex in people with knee osteoarthritis (OA) and whether there is an association between cortical organisation and accuracy of a motor task. METHODS: fMRI data were collected while 11 participants with moderate/severe right knee OA (6 male, 69 ± 6 (mean ± SD) years) and seven asymptomatic controls (5 male, 64 ± 6 years) performed three visually guided, variable force, force matching motor tasks involving isolated isometric muscle contractions of: 1) quadriceps (knee), 2) tibialis anterior (ankle) and, 3) finger/thumb flexor (hand) muscles. fMRI data were used to map the loci of peak activation in the motor cortex during the three tasks and to assess whether there were differences in the organisation of the motor cortex between the groups for the three motor tasks. Root mean square of the difference between target and generated forces during muscle contraction quantified task accuracy. RESULTS: A 4.1 mm anterior shift in the representation of the knee (p = 0.03) and swap of the relative position of the knee and ankle representations in the motor cortex (p = 0.003) were found in people with knee OA. Poorer performance of the knee task was associated with more anterior placement of motor cortex loci in people with (p = 0.05) and without (p = 0.02) knee OA. CONCLUSIONS: Differences in the organisation of the motor cortex in knee OA was demonstrated in relation to performance of knee and ankle motor tasks and was related to quality of performance of the knee motor task. These results highlight the possible mechanistic link between cortical changes and modified motor behavior in people with knee OA.

Proprioceptive impairments associated with knee osteoarthritis are not generalized to the ankle and elbow joints.

The mechanisms for proprioceptive changes associated with knee osteoarthritis (OA) remain elusive. Observations of proprioceptive changes in both affected knees and other joints imply more generalized mechanisms for proprioceptive impairment. However, evidence for a generalized effect remains controversial. This study examined whether joint repositioning proprioceptive deficits are localized to the diseased joint (knee) or generalized across other joints (elbow and ankle) in people with knee OA. Thirty individuals with right knee OA (17 female, 66±7 [mean±SD] years) of moderate/severe radiographic disease severity and 30 healthy asymptomatic controls of comparable age (17 female, 65±8years) performed active joint repositioning tests of the knee, ankle and elbow in randomised order in supine. Participants with knee OA had a larger relative error for joint repositioning of the knee than the controls (OA: 2.7±2.1°, control: 1.6±1.7°, p=.03). Relative error did not differ between groups for the ankle (OA: 2.2±2.5°, control: 1.9±1.3°, p=.50) or elbow (OA: 2.5±3.3°, control: 2.9±2.8°, p=.58). These results are consistent with a mechanism for proprioceptive change that is localized to the knee joint. This could be mediated by problems with mechanoreceptors, processing/relay of somatosensory input to higher centers, or joint-specific interference with cognitive processes by pain.

Postural response to vibration of triceps surae, but not quadriceps muscles, differs between people with and without knee osteoarthritis.

Although proprioceptive impairments are reported in knee osteoarthritis (OA), there has been little investigation of the underlying causes. Muscle spindles make an important contribution to proprioception. This study investigated whether function of quadriceps, triceps surae, and tibialis anterior muscle spindles is altered in individuals with knee OA. Thirty individuals with knee OA (17 females, 66 ± 7 [mean ± SD] years) and 30 healthy asymptomatic controls (17 females, 65 ± 8 years) stood comfortably and blindfolded on a force plate. Mechanical vibration (60 Hz) was applied bilaterally over the quadriceps, triceps surae, or tibialis anterior muscles for the middle 15 s (Vibration) of a 45 s trial (preceded and followed by 15 s Baseline and Recovery periods). Two trials were recorded for each muscle site. Mean anterior-posterior displacement of centre of pressure was analysed. Although there were no differences between groups for trials with vibration applied to the quandriceps or tibialis anterior, participants with knee OA were initially perturbed more by triceps surae vibration and accommodated less to repeated exposure than controls. This indicates that people with knee OA have less potential to detect or compensate for disturbed input to triceps surae, possibly due to an inability to compensate using muscles spindles in the quadriceps muscle.

A comparison of RULA, REBA and Strain Index to four psychophysical scales in the assessment of non-fixed work.

OBJECTIVES: The objective of this study was to evaluate the efficacy of three ergonomic assessment tools (EATs) (RULA, REBA and Strain Index (SI)) in the assessment of non-fixed work through comparison to four occupationally relevant Borg 10 psychophysical scales: Lifting Effort, Grasping Effort, Wrist Discomfort, and Low Back Discomfort. PARTICIPANTS: Fourteen male rodworkers participated in this study. The participants had at least six months experience and had no musculoskeletal injuries in the six months preceding their participation. METHODS: Psychophysical scale and video data were collected while participants performed non-fixed work on construction sites. Psychophysical and EAT outcome measure scores were calculated for a shortlist of tasks. RESULTS: It was found that the perceived Grasping Effort and Wrist Discomfort scales differentiated between the WMSD risks associated with rodworking tasks and SI was found to be more effective than RULA and REBA in the assessment of non-fixed work WMSD risks. CONCLUSIONS: Based on the findings of this study, it is suggested that SI be further evaluated for its ability to assess WMSD risks associated with non-fixed work tasks. SI presents results that have practical application to non-fixed occupations and differentiate between tasks based on the WMSD risks associated with the tasks.

Attentional demands associated with obstacle crossing while carrying a load.

The extent to which different locomotor tasks require cognitive control is not well characterized. In this article, the authors consider the potential increase in attentional demands associated with carrying an anterior load while clearing an obstacle. Nine healthy male volunteers participated in 80 walking trials, 20 in each of 4 conditions: 1 no load condition (NL) and 3 carrying conditions (2KG, 5KG, and 10KG). Of the 20 trials in each condition, 12 included a probe reaction time (PRT) test during lead limb obstacle crossing, which was used to measure cognitive load. A load-dependent increase in PRT was observed, with PRT in the 2KG condition being significantly greater than in the NL condition, and PRT in the 5KG and 10KG conditions being significantly greater than in the 2KG condition. These results suggested that cognitive load was increased when: (a) the obstacle was occluded from vision by the load, and (b) the magnitude of load was increased.