Abstract
The main aim was to explore the changes in hand-grip strength in patients with Duchenne muscular dystrophy (DMD) aged 5-29years. Secondary aims were to test the effect of mutation, ambulatory status and glucocorticoid use on grip strength and its changes over time and to compute the number of subjects needed for a clinical trial to stabilize grip strength. The analysis was performed on data collected during five international natural history studies on a cohort of DMD patients. Two hundred and two patients with genetically proven DMD were pooled from five different natural history studies. Excepting 13 patients with only one visit, the mean duration of follow-up was 2.2 ± 1.6years. A total of 977 measurement points were collected. Grip strength was measured on the dominant side with a high precision dynamometer. The analysis was performed using absolute values and normalized values expressed in percentage of predicted values for age. For absolute values, grip strength typically increased in ambulatory boys and decreased in non-ambulatory patients. However, when normalized, grip strength was already reduced at age 5years and thereafter continued to fall away from normal values. The weaker the patients, the less strength they are prone to lose over again. Grip strength constitutes a sensitive and continuous outcome measure that can be used across all stages of DMD. Its measurement is easy to standardized, can be used in ambulatory and non-ambulatory patients and does not present any floor or ceiling effect. It is thus attractive as an outcome measure in therapeutic trials.
Highlights
Duchenne Muscular Dystrophy (DMD) is a degenerative genetic muscle disease in which mutations in the dystrophin gene lead to muscle fiber degeneration and gradual replacement of muscle by fat and connective tissue
We showed that maximal grip strength expressed in percentage of predicted value counterbalances the cofounding effect of growth during childhood and can be used as continuous variable to measure the functional decline due to Duchenne muscular dystrophy across all stages of the disease
The analyses demonstrated the decrease of grip strength in a large population of Duchenne muscular dystrophy (DMD) patients aged from 5 to 30 years compared to normal values
Summary
Duchenne Muscular Dystrophy (DMD) is a degenerative genetic muscle disease in which mutations in the dystrophin gene lead to muscle fiber degeneration and gradual replacement of muscle by fat and connective tissue. Grip strength can be impaired from a young age in DMD, even long before the loss of ambulation [19, 25] It is correlated with the degree of physical disability [13, 21], is sensitive to change in the nonambulatory DMD population [21] and presents excellent reliability [22]. Maximal grip strength (MGS) measured with an appropriate handgrip dynamometer is a continuous variable that does not present any floor or ceiling effects in DMD [22]. These results have been observed on a rather limited number of patients and on a limited age range. We hypothesized that expressing MGS in percentage of predicted values rather than in absolute values could increase sensitivity to change by reducing the confounding factors of growth and maturation
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