Accelerometric outcomes of motor function related to clinical evaluations and muscle involvement in dystrophic dogs

PLoS One. 2018 Dec 11;13(12):e0208415. doi: 10.1371/journal.pone.0208415. eCollection 2018.

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by primary muscle degeneration. Patients with DMD reveal progressive muscle weakness leading to ambulatory dysfunction. Novel outcome measures are needed for more sensitive evaluation of therapeutic effects in clinical trials. Multiple parameters of acceleration and angular velocity are used as efficient indicators to quantify the motion of subjects, and these parameters have been recently applied for evaluation of motor function in DMD. In the present study, we evaluated gait in a dystrophic dog model, CXMDJ, by measuring three-axial acceleration and angular velocity over the course of months. Hybrid sensors were placed on the dorsal thoracic and lumbar regions of dogs to detect a wide range of acceleration (±8 G) and angular velocity (±1000 degrees per second). Multiple parameters showed lower values in dystrophic dogs compared to wild-type (WT) dogs, and declined over the course of months. Acceleration magnitude (AM) at the thoracic region in dystrophic dogs was prominently lower compared with WT dogs, even at the age of 2 months, the onset of muscle weakness, whereas AM at the lumbar region drastically declined throughout the disease course. The angular velocity index in the vertical direction in the lumbar region increased in dystrophic dogs, suggesting waddling at the girdle. These parameters also accordingly decreased with exacerbation of clinical manifestations and a decrease in spontaneous locomotor activity. The AM of dystrophic dogs was analyzed with magnetic resonance imaging to look for a correlation with crus muscle involvement. Results showed that acceleration and angular velocity are multifaceted kinematic indices that can be applied to assess outcomes in clinical trials for hereditary neuromuscular disorders including DMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Accelerometry* / methods
  • Accelerometry* / veterinary
  • Animals
  • Disease Models, Animal
  • Dog Diseases* / diagnosis
  • Dog Diseases* / physiopathology
  • Dogs
  • Female
  • Gait / physiology
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / veterinary
  • Male
  • Motor Activity / physiology
  • Muscle, Skeletal* / diagnostic imaging
  • Muscle, Skeletal* / physiopathology
  • Muscular Dystrophy, Animal* / diagnosis
  • Muscular Dystrophy, Animal* / physiopathology
  • Muscular Dystrophy, Duchenne / diagnosis
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / physiopathology
  • Predictive Value of Tests
  • Prognosis

Grants and funding

This study was supported by Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry intramural research grants 25-5 to Dr. Shin’ichi Takeda, Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry intramural research grants 28-6 to Dr. Shin’ichi Takeda, Japan Agency for Medical Research and Development (JP) 16ek0109154h0002 to Dr. Shin’ichi Takeda, Japan Agency for Medical Research and Development (JP) 18ek0109239h0002 to Dr. Yoshitsugu Aoki, and JSPS KAKENHI 18K07544 to Dr. Yoshitsugu Aoki. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.