Association of Elbow Flexor MRI Fat Fraction With Loss of Hand-to-Mouth Movement in Patients With Duchenne Muscular Dystrophy

Objective:To study the potential of quantitative MRI (qMRI) fat fraction (FF) as biomarker in non-ambulant Duchenne muscular dystrophy (DMD) patients, we assessed the additive predictive value of elbow flexor FF to age on loss of hand-to-mouth movement.Methods:Non-ambulant DMD patients (≥8 years) were included. 4-point Dixon MRI scans of the right upper arm were performed at baseline and at 12, 18 or 24 months follow-up. Elbow flexor FFs were determined from five central slices. Loss of hand-to-mouth movement was determined at study visits and by phone-calls every four months. FFs were fitted to a sigmoidal curve using a mixed model with random slope to predict individual trajectories. The added predictive value of elbow flexor FF to age on loss of hand-to-mouth movement was calculated from a Cox model with the predicted FF as a time varying covariate, yielding a hazard ratio.Results:Forty-eight MRIs of 20 DMD patients were included. The hazard ratio of a percent-point increase in elbow flexor FF for the time to loss of hand-to-mouth movement was 1.12 (95%-confidence interval 1.04-1.21; p=0.002). This corresponded to a 3.13-fold increase of the instantaneous risk of loss of hand-to-mouth movement in patients with a 10 percent-points higher elbow flexor FF at any age.Conclusion:In this prospective study, elbow flexor FF predicted loss of hand-to-mouth movement independent of age. qMRI measured elbow flexor FF can be used as surrogate endpoint or stratification tool for clinical trials in non-ambulant DMD patients.Classification of Evidence:This study provides Class II evidence that qMRI FF of elbow flexor muscles in patients with DMD predicts loss of hand-to-mouth movement independent of age.

A new approach of inducing proprioceptive illusion by transcutaneous electrical stimulation

Background Neurotraumas or neurodegenerative diseases often result in proprioceptive deficits, which makes it challenging for the nervous system to adapt to the compromised sensorimotor conditions. Also, in human machine interactions, such as prosthesis control and teleoperation, proprioceptive mismatch limits accuracy and intuitiveness of controlling active joints in robotic agents. To address these proprioceptive deficits, several invasive and non-invasive approaches like vibration, electrical nerve stimulation, and skin stretch have been introduced. However, proprioceptive modulation is still challenging as the current solutions have limitations in terms of effectiveness, usability, and consistency. In this paper, we propose a new way of modulating proprioception using transcutaneous electrical stimulation. We hypothesized that transcutaneous electrical stimulation on elbow flexor muscles will induce illusion of elbow joint extension. Method Eight healthy human subjects participated in the study to test the hypothesis. Transcutaneous electrodes were placed on different locations targeting elbow flexor muscles on human subjects and experiments were conducted to identify the best locations for electrode placement, and best electrical stimulation parameters, to maximize induced proprioceptive effect. Arm matching experiments and Pinocchio illusion test were performed for quantitative and qualitative analysis of the observed effects. One-way repeated ANOVA test was performed on the data collected in arm matching experiment for statistical analysis. Results We identified the best location for transcutaneous electrodes to induce the proprioceptive illusion, as one electrode on the muscle belly of biceps brachii short head and the other on the distal myotendinous junction of brachioradialis. The results for arm-matching and Pinocchio illusion tests showed that transcutaneous electrical stimulation using identified electrode location and electrical stimulation parameters evoked the illusion of elbow joint extension for all eight subjects, which supports our hypothesis. On average, subjects reported 6.81° angular illusion of elbow joint extension in arm-matching tests and nose elongated to 1.78 × height in Pinocchio illusion test. Conclusions Transcutaneous electrical stimulation, applied between the the synergistic elbow flexor muscles, consistently modulated elbow joint proprioception with the illusion of elbow joint extension, which has immense potential to be translated into various real-world applications, including neuroprosthesis, rehabilitation, teleoperation, mixed reality, and etc.

22 Volumetric MRI; A Potential Outcome Measure of Muscle Reinnervation

Introduction Improved outcome measures of muscle reinnervation would facilitate clinical translation of new therapies which hope to enhance human peripheral nerve repair. Valid outcome measures should be receptive to the biological process of muscle reinnervation and correlate with clinical assessments of muscular function. This study investigated the responsiveness of volumetric MRI to the biological process of muscle reinnervation and its relationship with clinical indices of muscular function. Method Twenty-five patients who underwent nerve transfer to reinnervate elbow flexor muscles were followed-up at a median time of 258 days (-86 to 1698 days) post-operatively for a mean of two (one to three) volumetric MRI assessments. Medical Research Council (MRC) grade, peak volitional force (PVF), muscular fatigue, co-contraction and Stanmore Percentage of Normal Elbow Assessment (SPONEA) was also measured at each appointment. The responsiveness of each parameter was compared using Pearson or Spearman correlation as appropriate. Results Elbow flexor muscle volume per unit BMI demonstrated responsiveness to the biological process of muscle reinnervation (R2=0.73, p < 0.001) and correlated with patient reported impairments of reinnervated muscle; co-contraction (R2=0.63, p = 0.02) and muscle fatigue (R2=0.64, p = 0.04). Conclusions Volumetric MRI may is an excellent candidate as an outcome measure of muscle reinnervation.