An integrated approach in a case of facioscapulohumeral dystrophy

Selective muscle atrophy with weakness and early fatigue [1] are main features of facioscapulohumeral dystrophy (FSHD), the third most common muscular dystrophy (MD).

No therapy is available for FSHD. Nevertheless, patients usually report some improvement related to physical exercise and the use of nutritional supplements (NS). These effects are not currently substantiated by appropriate investigations. In particular the effect of exercise training has not been fully examined mainly due to concerns that it may trigger disease progression. However recent observations suggest that in FSHD post-exercise creatine kinase (CK) elevation (indicator of muscle damage) normalizes within one day compared with the pre-exercise values [2].

Again, the role of NS in MD remains to be elucidated. Recent observations suggest that among supplements creatine and Branched Chain Amino Acids (BCAA) may exert positive effects as they may act by limiting exercise-induced injury [3]. The positive changes due to creatine appear to be safely enhanced by coadministration of conjugated linoleic acid (CLA) [4].

The aim of this case report is to show the effects of a controlled exercise training and NS in a FSHD patient.

A 43-year-old wheelchair-bound woman from 2006, affected by FSHD, underwent 6-month exercise therapy associated with NS to study metabolic and possible changes in motor function related to the program.

The patient was born from uneventful pregnancy and delivery to non-consanguineous parents, with family history negative for MD.

The patient carries a “de novo” D4Z4 reduced allele with 2 repeats (14 kb).

When she was 2 yrs her parents noted difficulty of walking and waddling gait. At 4 she was diagnosed having a muscle disease. At 11 she was clinically diagnosed with a progressive MD. At 30 neurological examination revealed left steppage gait, facial weakness, atrophy of shoulder girdle muscles with bilateral scapular winging, atrophy of bilateral pectoralis, infraspinatus and supraspinatus muscles, moderate biceps brachii and severe deltoid weakness, foot extensor weakness and proximal hip weakness, lumbar hyperlordosis; lower extremities tendon reflexes were absent, sensory examination was normal. In 1982 a muscle biopsy revealed myopathic changes compatible with FSHD.

Presently she presents severe muscle hypotrophy and proximal-distal weakness leading to loss of ambulation in 2006 and severe lumbar hyperlordosis (FSHD score 12 according to Lamperti et al. [5]).

In 2001 respiratory function assessment first revealed mild respiratory restrictive insufficiency (%pred: VC 75.9; FVC 82.3; FEV1 88.50; FEV1%/VCmax 133, see Figure 1).

The patient (180 cm, 71.4 Kg) participated in the study after providing written informed consent. Procedures were conducted according to the Declaration of Helsinki. The protocol had a duration of 6 mo, 4 days/week. Before and after exercise and nutrition intervention the following evaluations were performed:

At the end of the protocol we observed an improvement of the patient’s nutritional status as demonstrated by significant improvement of anthropometric (BMI, FFM) and biochemical (serum proteins) parameters. In particular a reduction of body mass (−13.17%) associated with reduced fat mass (FM, −8%) and improved fat free mass (FFM +8%) was found (Table 1). Indeed beneficial changes in biochemical blood parameters included increased total protein concentration, albumin percentage, and albumin/globulin ratio which were reported to normal values (Table 1). Functionally a modest increase of peak force was observed only in shoulder abductors bilaterally whereas no change was observed in elbow flexors and extensors (Table 1). An amelioration of peak oxygen consumption (VO_2peak), ventilation exchange, and an improvement of Borg score during submaximal exercise suggested the appearance of a certain degree of muscular adaptation to training and possibly an amelioration of the oxidative metabolism (Table 1). This was demonstrated by increased time/power to exhaustion during incremental test. Finally after intervention substantial steadiness of several PFTs in comparison with initial evaluation (FVC before: 69.6, after 67.4; VC: 68.7 before, 70.4 after; FEV1 before 68.2; after 68.5; FEV1/FVC% before 104.9, after 108.8) was observed (Figure 1).

Results from our report suggest that a specific exercise therapy and supplementation program can be safely used in selected FSHD patients but the relative contribution of the adopted interventions, exercise and dietary supplementation, and whether their synergy may contribute to the observed improvements remains unknown and deserves future controlled studies.

Physical exercise may represent one possible way to counteract atrophy and fatigue in FSHD but its effects have not been fully investigated due to concerns that it may ultimately trigger disease progression. Recent meta analysis suggests that moderate-intensity strength training does not appear to harm individuals with FSHD, but there is insufficient evidence that it provides benefits [12]. However initial observations have shown that at least aerobic training is beneficial [13].

The concept that NS might have effects in prevention or treatment of MD is experiencing a new revival [11]. However the lack of unequivocal results and flaws in the choice of supplements and protocols to be adopted leads to an assumption mostly based on empirical attitude. Among supplements creatine and BCAA may exert positive effects as they act by limiting load-induced muscle injury. In particular creatine improves muscle mass and performance in combination with strength training [14] and attenuates exercise-induced alteration of markers of cell death/lysis [15] whereas BCAA may act by maximizing protein synthesis [4]. Actually, the only creatine trial in MD, including FSHD, showed a small but significant improvement of 3% in muscle strength and 10% in daily life activities [16]. No clinical BCAA trials are currently available.

These very preliminary indications suggest positive effects of training and selected supplements in muscle disease [4], therefore we applied an integrated approach based on endurance/strength and respiratory training combined with NS with BCAA and creatine + CLA for six months.

In this context, here we compared the results of this approach on physical capacity and blood profile of a 43y old wheelchair bound FSHD patient with severe proximal and distal muscular impairment, and moderate restrictive respiratory insufficiency.

In particular, our study revealed an improvement of blood protein profile, body mass and composition, and an amelioration of peak oxygen consumption whereas no change in resting energy expenditure was observed. Furthermore after initiation of the exercise nutrition intervention, several PFTs demonstrated stable values. Importantly, the program was well tolerated by the patient as no muscle soreness, change in CK serum levels or intolerance to supplements were observed.

The participant signed a consent approved by which informed the participant that the data would be published in medical journals without personally identifiable information. A copy of the signed informed consent is available for review upon request.