Myotonic dystrophy type 1 alters muscle twitch properties, spinal reflexes, and perturbation‐induced trans‐cortical reflexes
Authors: Shields Richard K. , Dudley-Javoroski Shauna A. , Lee Jinhyun , Dubey Olga , McCue Patrick M. , Johnson Kristin A. , Buelow Aaron , Petrie Michael Arlyn , Cross Stephen , Gutmann Laurie , Nopoulos Peggy 
Published: April 2020

Myotonic dystrophy type 1 (DM1) is a common inherited muscular dystrophy in adults involving a mutation of DM1 protein kinase (DMPK) with widespread effects in skeletal muscle, cardiac muscle, and the central nervous system. There are significant knowledge gaps regarding neuromuscular physiology in people with DM1. Clinically, people with DM1 are characterized by a muscle impairment scale (MIRS); however, there is no gold standard for the neurophysiologic assessment of disease severity for people with DM1. Our goal is to establish new neurophysiologic measures that correlate with neuromotor task performance in people with DM1. These assessment can provide insight into how therapeutic agents may yield tangible functional outcomes for people living with DM1.PurposeThe purpose of this study is to characterize muscle twitch properties, spinal segmental reflexes (H‐reflexes), and trans‐cortical reflexes (LLRs) during visuomotor tracking task in a cohort with clinically‐mild to moderate DM1.Methods24 and 25 people with and without DM1 participated in this study. H‐reflexes were measure by delivering 2 stimulus pulses (H1 and H2) 500ms apart to the tibial nerve and monitoring soleus muscle responses. A single and doublet (160Hz) pulses were delivered by surface electrodes over the calf muscle. Quadriceps LLRs were elicited by delivering an unexpected perturbation during a single‐limb squat (SLS) visuomotor tracking task. Assessments were correlated to DM1 diagnosis from genetic testing using CTG Allele 1 repeat number. All participants provided written consent approved by the University of Iowa Institutional Review Board in compliance with the Declaration of Helsinki.ResultsDM1 was associated with partial loss of H‐reflex homosynaptic depression. H2 was significantly larger as a function of H1 for the DM1 group compared to the control group (p=0.05). Doublet stimulation was enhanced, yielding an elevated double‐single twitch ratio (DSR) (p=0.034) in DM1 group. A significant relationship existed between DSR and the MIRS score for people with DM1 (p<0.001, R2=0.625). Participants with DM1 demonstrated greater error during the SLS task(p<0.001). DM1 individuals with the least‐robust LLR responses showed the greatest loss of spinal H‐reflex depression (p=0.05, R2=0.248).ConclusionsNeurophysiologic assessments of DM1 impairment are needed to link the pathomechanisms of the disease to clinical measures of physical function. DM1 is associated with abnormalities of muscle twitch properties suggestive of excitation‐contraction uncoupling. Co‐occurring alterations of spinal and trans‐cortical reflex properties underscore the central nervous system manifestations of this disorder. H‐reflex homosynaptic depression and spinal trans‐cortical reflexes are clinically feasible to test and they warrant further investigation as correlates of motor function in DM1. These assessments will be essential tools to gauge the efficacy of future therapies upon the CNS manifestations of DM1.Support or Funding InformationThis study was supported in part by NIH Grants R01 NS094387, R01 HD084645, R01 HD082109, and CTSA UL1TR002537.