Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by the degeneration of motor neurons in the anterior horn of the spinal cord, due to the absence of the SMN1 gene and the resulting lack of SMN protein. Some patients with particularly severe forms (types 0 or 1) die before the age of 2 in the absence of treatment, while others retain autonomous walking throughout their lives, with no reduction in life expectancy. Three treatments aimed at restoring SMN (TRS) protein expression have recently been approved by the US Food and Drug Administration and the European Medicines Agency (i.e. Nusinersen / Onasemnogene Abeparvovec / Risdiplam). Patients treated with TRS after the onset of symptoms (symptomatic patients) may show significant motor improvement, but retain difficulties such as muscle weakness and fatigue leading to limitations in activities of daily living. The aim of this study is to adapt a fatigability test, widely validated in its original version in different populations (QIF test), but adapted in this protocol to the motor level and low abilities of certain SMA patients. Our objectives are to determine whether these assessments are feasible in SMA patients, reproducible, and relevant for monitoring this population, either routinely or for future clinical trials.
Genetically confirmed spinal muscular atrophy
Age ≥ 6 years
No orthopaedic surgery in the 6 months prior to inclusion
Informed consent signed by the patient(s) or parent(s)/legal guardian(s) and assent of the patient
Other condition that may significantly interfere with the assessment of the SMA and which is clearly unrelated to the disease
Other associated neurological disease
Joint deformities that prevent correct and comfortable positioning with the various different measuring devices (thumb-index clamp, handgrip and QIF-test)
Contraindication to transcranial magnetic stimulation
Crossover
Thumb test
Other interventionThumb adduction test consisting of intermittent, repetitive isometric contractions lasting 5 seconds at incremental percentages of maximum force.
Grip test
Other interventionMuscle contraction gripping test, consisting of intermittent, repetitive isometric contractions lasting 5 seconds at incremental percentages of maximum force.
Quadriceps Intermittent Fatigue test (QIF test))
Other interventionQuadriceps muscle contraction test consisting of intermittent, repetitive isometric contractions lasting 5 seconds at incremental percentages of maximum force.
Feasibility of a fatigability test adapted to the motor level of the entire population of patients with spinal muscular atrophy.
Feasibility will be assessed by the patient's success in performing the fatigability test: i.e. performing at least 2 incremental steps (i.e. at least 10 contractions at 10% of their maximum strength, then 10 contractions at 20% of their maximum strength). Validation of the feasibility of the fatigability test will be obtained if at least 80% of patients are able to perform at least the first 2 stages.
Tolerance of fatigability test - Pain
The tolerance of the fatigability test will be measured by a visual analogue pain scale for adults and the FPS-R face scale for children, as recommended by the French National Authority for Health (HAS)
Tolerance of fatigability test - RPE
The tolerance of the fatigability test will be measured by perception of exertion (RPE) using the Borg scale (from 0 - rest to 10 - Maximal perceived effort).
Tolerance of fatigability test - AEs
The tolerance of the fatigability test will be measured by the recording of adverse events (AEs) such as pain, discomfort, cramp; before, at each stage and at the end of the test. Tolerability of the fatigability test will be achieved if at least 90% of patients are able to carry out the test without having to stop it early because of the occurrence of AEs.
Reproducibility of the fatigability test
The reproducibility of the fatigability test will be assessed by measuring and comparing the maximum voluntary force (MVC, en Nm) and the loss of force, assessed by the same assessor.
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