RESUMO
Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12 month, longitudinal, observational study. Here, we report the baseline data. A 20 mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25 years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r = 0.517, P < 0.0001 and r = 0.764, P < 0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.
RESUMO
PURPOSE: Determine the feasibility and utility of using a battery of tests utilized, so far, to assess neurological-cognitive functions in the typical adult population and identify the spectrum of these functions in adult SBM patients. METHODS: Prospective study in which 15 participants (mean age = 28.7 ± 8.7 years, range = 19-45 years) completed the targeted battery of tests (n = 5-15/test) previously standardized to the general population. Results were compared with normative data. RESULTS: Statistically significant differences with normative means were noted in the following tests: Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), and NIH Toolbox Fine Motor (Dexterity and Grip Strength) tests. Cohort means for NIH Toolbox Fluid, Crystallized, and Cognitive Composite Scores and Timed Up and GO (TUG) were not different from normative means. CONCLUSION: All tests were successfully completed by cohort. Whereas many aspects of cognition were normal, tests assessing visual-constructural, calculation, motor, and fluency functions did show differences from population means. Numerous tests assessing multiple domains are needed and can be used in future aging studies to appreciate the spectrum of cognitive and motor abilities in adults with SBM.