Gait and Quality of Life in DM1
Disturbances of gait are an important component of the burden of disease in DM1—a patient/family member survey conducted in conjunction with the Myotonic Dystrophy Voice of the Patient Report identified difficulty with mobility as the second most impactful symptom affecting quality of life. Quantitative assessment of gait disturbances is viewed as a means of improving patient management (Bachasson et al., 2016; Pucillo et al., 2018) and is being incorporated as an outcome measure in interventional clinical trials (Bassez et al., 2018). Given the multifactorial regulation of gait, the understanding of contributing mechanisms, functional consequences, and potential therapeutic strategies represents an important unmet need for DM1.
Moving Beyond Muscle Weakness in Understanding Gait Disturbances
In a new publication (Naro et al., 2019), it is posited that a ‘simple’ explanation for disturbances of gait and balance—that both are directly related to the degree of muscle weakness—is viewed as misleading. Instead, Dr. Rocco Salvatore Calabrò (IRCCS Centro Neurolesi Bonino Pulejo) and colleagues have tested the hypothesis that gait disruptions in DM1 are a consequence of deterioration of CNS-skeletal muscle network, disrupting the synergy of muscle group activation.
In this study, the research team utilized time-frequency spectral coherence analysis of surface EMG readouts from eight lower limb muscles during walking. Using this approach, they could assess the status of multiple muscle group/network coordination as it relates to the disturbances in gait—muscle impairment versus CNS damage was evaluated. The group also assessed the link between postural control and gait disturbance using electronic baropodometry.
The research team assessed seven adult DM1 patients and ten controls. Assessment of muscle activation during ambulation was measured using surface emg recordings bilaterally from four proximal and distal lower limb muscles. A gait quality index was calculated from accelerometer data. Electronic baropodometer analysis informed quality of stance control.
All DM1 patients exhibited gait disturbances—gait cycles were longer, step cadence lower, and pace slower than controls—and disrupted balance. Muscle network pattern analysis showed disruption of the connectivity between distal muscles both within and between legs in DM1 versus healthy controls. Analysis of signal synergy in DM1 showed that muscle activation patterns varied from one gait cycle to another versus consistent activation patterns across cycles in controls. While muscle weakness correlated with stability of stance (postural control), there was no correlation between weakness and muscle connectivity or synergy data.
Modeling the Etiology of Gait Disturbances in DM1
Taken together, the research team utilized a novel muscle connectivity analytic approach and showed that patients with DM1 exhibit: deteriorated muscle network organization at temporal and spatial levels, reflecting disruption at a central neural network level; greater network integration but reduced network segregation, which they suggest may reflect reduced CNS ability to segregate signals to distinct motor control modules; and, overall, a reduced availability of motor repertoires resulting in greater gait cycle variability.
Importantly, the team found no correlation between muscle weakness and a disruption of muscle connectivity characteristic of DM1—instead DM1 appears to be characterized by deterioration of neuromuscular networks unrelated to the development of individual muscle weakness.
Based upon a model that is emerging from these studies, an understanding of neuromuscular network changes, particularly that originating from signal synergy deterioration in the CNS that underlie gait disturbances, is essential to development of effective rehabilitation programs for patients living with DM1. This understanding also may be critical to how we view DM1 in the development of candidate therapies and design of interventional clinical trials.
Relationship between muscle impairments, postural stability, and gait parameters assessed with lower-trunk accelerometry in myotonic dystrophy type 1.
Bachasson D, Moraux A, Ollivier G, Decostre V, Ledoux I, Gidaro T, Servais L, Behin A, Stojkovic T, Hébert LJ, Puymirat J, Eymard B, Bassez G, Hogrel JY.
Neuromuscul Disord. 2016 Jul;26(7):428-35. doi: 10.1016/j.nmd.2016.05.009. Epub 2016 May 12.
Modified dynamic gait index and limits of stability in myotonic dystrophy type 1.
Pucillo EM, Mcintyre MM, Pautler M, Hung M, Bounsanga J, Voss MW, Hayes H, Dibella DL, Trujillo C, Dixon M, Butterfield RJ, Johnson NE.
Muscle Nerve. 2018 Nov;58(5):694-699. doi: 10.1002/mus.26331. Epub 2018 Sep 23.
Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial.
Bassez G, Audureau E, Hogrel JY, Arrouasse R, Baghdoyan S, Bhugaloo H, Gourlay-Chu ML, Le Corvoisier P, Peschanski M.
Brain. 2018 Oct 1;141(10):2855-2865. doi: 10.1093/brain/awy231.
Paving the way for a better understanding of the pathophysiology of gait impairment in myotonic dystrophy: a pilot study focusing on muscle networks.
Naro A, Portaro S, Milardi D, Billeri L, Leo A, Militi D, Bramanti P, Calabrò RS.
J Neuroeng Rehabil. 2019 Sep 18;16(1):116. doi: 10.1186/s12984-019-0590-0.