Facioscapulohumeral dystrophy (FSHD) is the third most common inherited neuromuscular disorder. It is an autosomal dominant slowly progressive myopathy with a variable age of onset, mostly in the second or third decade of life. Its yearly incidence rate is approximately 1:20.000 [1
]. The disease primarily affects the facial muscles, the muscles of the shoulder girdle (most typically the scapula stabilizers) and various leg muscles, while pelvic and trunk muscles are eventually affected as well [2
]. The pattern of muscle weakness is often asymmetrical, and the rate and extent of progression may vary considerably with sudden periods of unexplained rapid disease progression. In a small percentage of the patients, even respiratory insufficiency may occur [5
]. Only very recently, evidence became available that there may be a selective involvement of the central nervous system as well, in terms of decreased grey matter volume [6
] and reduced intracortical inhibition [7
]. Although FSHD is associated with a partial deletion of a critical number of repetitive elements (D4Z4) on chromosome 4q35, to date no causal gene has been identified and no curative treatment is available [3
]. FSHD may eventually lead to serious disabilities of speech, swallowing, reaching, standing and walking, even in early adulthood. Twenty percent of the patients become wheelchair bound. Since no cure is available, rehabilitation is the mainstay of treatment [2
Only recently it was shown by our group that severe fatigue, defined as a score equal or higher than 35 on the subscale fatigue of the Checklist Individual Strength (CIS-fatigue), was reported by 61% of the patients with FSHD. These severely fatigued patients had more problems with physical and social functioning as well as with mental and general health than similar patients without a severe fatigue. They also had more problems with concentration, initiating and planning [10
]. As such, experienced fatigue should be clearly distinguished from muscle weakness, which is probably the most common and characteristic symptom of FSHD [11
]. In a longitudinal study, we built a model of perpetuating factors for fatigue in patients with FSHD (figure ). It appeared that lack of physical activity, sleep disturbances and pain all contributed to experienced fatigue. In addition, loss of muscle strength and pain contributed to fatigue through a lower level of physical activity. Ultimately, experienced fatigue and physical inactivity both contributed to the level of societal participation [12
]. Thus, theoretically, in order to improve societal participation one should improve muscle strength, reduce pain, optimize physical activity and alleviate experienced fatigue. In addition, falling appears to be a major problem among FSHD patients. Our group was able to show that 65% of the patients reported falling at least once a year [13
]. Since fall incidents often lead to fear of falling and avoidance behaviour, they have a serious negative impact on physical activity and participation.
Model of perpetuating factors of experienced fatigue in patients with FSHD.
Improving muscle strength by strength training and/or (anabolic) medication has shown not to be successful in patients with FSHD [14
]. Until now, only one trial has investigated low-intensity aerobic exercises, indicating that aerobic training is a safe method to increase exercise performance [14
]. Although, in general, physical activity does not appear harmful [16
], more research is needed to establish whether AET is beneficial in patients with FSHD. Besides improving physical (aerobic) capacity, it seems important to optimize physical activity and change behaviour in daily life. Indeed, symptoms and signs of muscle weakness and fatigue as well as the anticipation of a (further) decline in physical capacity may elicit an inactive life-style, which may disproportionally affect physical activity, fatigue and societal participation. From this perspective, it might be beneficial to alter illness cognitions and coping styles by means of CBT. However, evidence for the effectiveness of CBT in patients FSHD is not yet available.
The primary objective of the FACTS-2-FSHD trial is:
- to study the efficacy of AET and CBT for decreasing chronic fatigue in patients with FSHD. It is hypothesized that both AET and CBT are more effective in decreasing fatigue than usual care, which is no therapy at all or occasional (conventional) physical therapy. The improvement by AET may be obtained through enhancement of physical (aerobic) capacity, whereas beneficial effects of CBT may be achieved through changes in daily activities and behaviour. By changing illness cognitions and improving coping style, the balance between actual behaviour and physical capacity will be optimized. Since changes achieved by CBT are more 'intrinsic', possible beneficial effects of CBT may last longer than those of AET.
Secondary objectives of the FACTS-2-FSHD trial are:
- to evaluate the effects of AET and CBT on bodily functions and structures as defined by the International Classification of Functioning, Disability and Health (ICF): lower extremity muscle strength, pain, psychological well being, cardiovascular risk factors, aerobic exercise tolerance, sleeping pattern, as well as biomarkers in blood and urine and structural and metabolic muscle tissue characteristics.
- to evaluate the effects of AET and CBT on the ICF level of activities: physical activity in daily life, self perceived functional status, and fall incidence.
- to evaluate the effects of AET and CBT on the ICF level of participation: limitations in participation and autonomy and quality of life.
- to evaluate the effects of AET and CBT on environmental and personal factors as defined by the ICF: coping style, illness cognitions, concentration problems, motivation, caregiver strain, experienced fatigue of the caregiver, social support and coping of the caregiver.