Longitudinal evaluation of fatigue in adult patients with spinal muscular atrophy and the impact of disease-modifying drugs

Fatigue is a frequent and under-recognized symptom in adults with spinal muscular atrophy (SMA). Although motor scales can detect disease progression, they may be insufficiently sensitive over short observation periods, particularly in patients with slower progression.To assess the prevalence and longitudinal course of fatigue in adult SMA patients using validated instruments. General perceived fatigue was assessed using the Fatigue Severity Scale (FSS), while the Modified Fatigue Impact Scale (MFIS) was used to evaluate multidimensional fatigue-comprising the physical, cognitive, and psychosocial domains. Additionally, we explored associations with motor function, neurophysiological parameters, and treatment status.Twenty-five adults with genetically confirmed SMA were evaluated at baseline and after one year using the FSS and MFIS. Motor function was measured by the Hammersmith Functional Motor Scale - Expanded, Revised Upper Limb Module (RULM), and Motor Function Measurement (MFM); neurophysiological assessment included Compound Muscle Action Potential (CMAP), Motor Unit Number Index (MUNIX) and repetitive nerve stimulation. Patients were stratified by fatigue status and use of disease-modifying therapies.Significant fatigue (FSS > 4) was observed in 60% of patients at baseline and 56% at follow-up. After 1 year, the prevalence of fatigue was significantly lower in treated patients (33.3%) compared to untreated ones (75%; <i>p</i> = 0.04). The MFIS scores remained stable across the physical, cognitive, and psychosocial domains. No associations were found between fatigue severity and age, disease duration, motor scale scores, or neurophysiological parameters.Fatigue is highly prevalent in adults with SMA and does not correlate with disease severity or motor/neurophysiological measures. Patients receiving disease-modifying therapies showed lower fatigue frequency, reinforcing the relevance of fatigue as a meaningful patient-reported outcome in this population.