Strength training and albuterol in facioscapulohumeral muscular dystrophy E.L. van der Kooi, MD; O.J.M. Vogels, MD, PhD; R.J.G.P. van Asseldonk; E. Lindeman, MD, PhD; J.C.M. Hendriks, PhD; M. Wohlgemuth, MD; S.M. van der Maarel, PhD; and G.W. Padberg, MD, PhD Abstract—Background: In animals and healthy volunteers 2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) albuterol may exert anabolic effects. The authors evaluated the effect of strength training and albuterol on muscle strength and volume in FSHD. Methods: Sixty-five patients were randomized to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks albuterol (sustained-release, 8 mg BID) was added in a randomized, double-blind, placebo-controlled design. Primary outcome was maximum voluntary isometric strength (MVIC) at 52 weeks. Secondary outcomes comprised dynamic strength and muscle volume. Results: Training and albuterol were well tolerated. Training of elbow flexors did not result in a significant effect on MVIC, but dynamic strength improved significantly. Elbow flexor MVIC strength increased significantly in albuterol vs placebo treated patients. Ankle dorsi- flexor strength decreased in all groups. Eleven out of twelve non-trained muscles in the albuterol group showed a positive effect on MVIC compared to the placebo group (p  0.05 in seven muscle groups). Muscle volume decreased in the placebo-treated, and increased in the albuterol-treated patients. No synergistic or antagonistic effects were observed between training and albuterol. Conclusions: In FSHD strength training and albuterol appear safe interventions with limited positive effect on muscle strength and volume. Consequences of prolonged use are presently unclear, which precludes routine prescription. NEUROLOGY 2004;63:702–708 With its estimated prevalence of 1 per 20,000, fa- cioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy after Duchenne dystrophy and myotonic dystrophy. 1 Al- though its association with a reduction in number of D4Z4 repeat units at 4q35 was recognized in 1991, 2,3 the pathogenic mechanisms relating this deletion to the phenotype are unclear. The decline in muscle strength and mass is progressive over years and fol- lows a general pattern of clinically affected muscles, but there is a large, unexplained, interindividual variability in rate of progression, even within those sharing the same mutation. 1 The variable course within families and the typical asymmetric weakness led to the hypothesis that daily exertion might be responsible for disease progression. 4,5 Four published studies on the effects of strength training in neuro- muscular disorders included as few as 13 FSHD patients. 6-9 Data on muscle strength in these FSHD patients suggest a positive effect of strength training and do not point toward susceptibility to muscle in- jury. However, limitations in design of these studies preclude firm conclusions. The benefit of strength training in FSHD patients is not defined. In animals and healthy volunteers 2-adrenergic agonists, such as clenbuterol and albuterol, increase muscle strength and muscle mass through their influ- ence on muscle protein metabolism and contractile ac- tivity. 10 In a pilot study and a subsequent randomized, controlled trial in FSHD patients albuterol induced a moderate gain in isometric muscle strength and lean body mass when used for 12 to 26 weeks. 11,12 After 52 weeks of medication lean body mass was still in- creased, but patients failed to retain the gain in strength. These findings suggest an anabolic effect that wears off with prolonged use. The strength-increasing effect of 2-adrenergic agonists might be augmented when the 2-sympathicomimetic is administered in combination with resistance exercise. 13-16 Because we expected an additive effect of training on the effect of the 2-adrenergic agonist albuterol, we undertook a trial to evaluate the efficacy of strength training, albuterol, and the combination of Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Con- tents for the August 24 issue to find the title link for this article. From Neuromuscular Center Nijmegen (Drs. van der Kooi, Wohlgemuth, and Padberg, and R.J.G.P. van Asseldonk) and Department of Epidemiology & Biostatistics (Dr. Hendriks), University Medical Center Nijmegen; Department of Neurology (Dr. Vogels), St Antonius Hospital, Nieuwegein; Rehabilitation Center De Hoogstraat and Rudolf Magnus Institute of Neuroscience (Dr. Lindeman), Rehabilitation Section, University Medical Center, Utrecht; and Department of Human and Clinical Genetics (Dr. van der Maarel), Leiden University Medical Center, Leiden, The Netherlands. Supported by a government grant of the Health Research and Development Council of the Netherlands (ZON-MW), the Prinses Beatrix Fonds, the Dutch Public Fund for Neuromuscular Disorders (VSN), and the Dutch FSHD Foundation. Received November 12, 2003. Accepted in final form April 29, 2004. Address correspondence and reprint requests to Dr. E.L. van der Kooi, Neuromuscular Center Nijmegen, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands; e-mail: e.vanderkooi@neuro.umcn.nl 702 Copyright © 2004 by AAN Enterprises, Inc.