Fatigability in Spinal Muscular Atrophy

Spinal muscular atrophy(SMA) is a disorder characterized by degeneration of the
motor neuron. It has a wide range of severity, ranging from neonatal
respiratory insufficiency and death (SMA type 1), inability to walk
independently (SMA type 2), problems with or loss of ambulation (SMA type 3) to
mild impairments in adults (SMA type 4). Fatigability, defined as the decline
in performance during and after prolonged motor tasks, is a common symptom in
addition to weakness. Recently, it was shown that neuromuscular junction (NMJ)
dysfunction is present in 50% of patients with SMA, which may be one of the
causes of fatigability. There is no curative treatment for SMA. Possible
treatment options for fatigability are drugs that improve the function of the
NMJ or exercise training (ET) that may reverse some of the detrimental effects
of inactivity in patients with neuromuscular disorders. Intervention study
design is complicated by the lack of reliable outcome measures for fatigability
in patients with SMA. To test the efficacy of possible treatment strategies
for fatigability in SMA patients we first need to develop reliable and of valid
outcome measures to assess fatigability in SMA patients and to explore
associations between fatigability and neuromuscular dysfunction

To determine the reproducibility and validity of specific outcome measures for
skeletal and respiratory fatigability in subjects with SMA.

psychometric study on reproducibility and validity

Measurements will be distributed over three different days and will take
approximately 90 minutes each time. Two measurements will be performed at the
participant home or at the exercise laboratory, depending the subjects*
preference. One measurement (T1 figure 2) will be performed at the exercise
laboratory. All subjects will perform several tests to measure skeletal and
respiratory fatigability. They will undergo measurement of height, bodyweight,
lung function and muscle function and fill out questionnaires about fatigue and
fatigability twice at home. The risks of these tests are negligible. Similar
tests used in usual care are well tolerated in other patient groups with
neuromuscular disorders.
Patients with SMA >= 12 years will be asked to undergo a short non-invasive EMG
protocol with repetitive nerve stimulation (RNS) of the ulnar (hand muscle)
and accessory (shoulder) nerves to document dysfunction of the neuromuscular
junction. This same protocol was well-tolerated in a previous study on SMA
patients performed by our research group in this hospital1 (MET_Utrecht
10-357). RNS is also frequently used in the workup of patients with
neuromuscular disease. RNS is often experienced as a short prickling or itchy
feeling. The protocol will be limited to 2x10 minutes which includes
preparations such as attaching surface electrodes. RNS will be performed in
short runs lasting 10-20 seconds. The burden of repetitive nerve stimulation
can be considered as minor. Importantly, subjects will also be included if they
do not want to undergo an EMG. The criteria of the Nederlandse Vereniging voor
Kindergeneeskunde (Dutch association of Paediatrics) concerning research
involving children will be strictly applied.
There are no direct benefits for the participants. However, being able to
measure fatigability will enable researchers to develop drugs and exercise
training programs aimed at this specific group of children in order to reduce
fatigability and improve daily life functioning. A previous survey has
indicated that patients with neuromuscular disorders including SMA give high
priority to research aiming at investigating the effects of care, including
training in addition to research on a potential cure