Perceived Fatigue in Spinal Muscular Atrophy: A Pilot Study

Abstract

Background: Fatigue is a common complaint in spinal muscular atrophy (SMA). Fatigability is well described in ambulatory SMA but the relationship to perceived fatigue has not been evaluated. Understanding this relationship has proven challenging for most disorders. Objective: To assess the relationship of perceived fatigue to fatigability, function, and quality of life in SMA. Methods: Thirty-two participants with SMA (21.9% type 2, 78.1% type 3) were recruited. Perceived fatigue and fatigability, function, and quality of life were assessed using standardized questionnaires and assessments. Associations were analyzed using Pearson correlation coefficients (p = 0.05). Also, the effects of age, type, and ambulatory status were determined on perceived fatigue. Results: All SMA participants reported fatigue. Perceived fatigue was not associated with function, quality of life, or fatigability in ambulatory SMA patients. Neither age, type, nor ambulatory status influenced perceived fatigue. Conclusions: Perceived fatigue can be quantified in SMA. Interestingly, perceived fatigue did not correlate with fatigability or function, suggesting that cognitive, homeostatic, or psychologic factors may be more relevant as co-morbid factors. Clinical trials targeting perceived fatigue in SMA should focus on these patient-reported assessments. A multilevel approach is required to separate the various mechanisms involved in perceived fatigue.

An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment

“…The MFI, on the other hand, addresses the perceived physical condition in general rather than fatigue following exercise and might, therefore, be more sensitive in SMA patients (for example item 2: "Physically I feel only able to do a little" or item 14: "Physically I feel I am in a bad condition"). In accordance with previous reports regarding fatigue in general [14,21,25], physical fatigue did not correlate with disease severity or motor function in our cohort. Nevertheless, it was associated with deteriorated HRQOL as previously described for fatigue in motor neuron diseases [49], while HRQOL itself correlated positively with measures of motor function.…”

“…As fatigue is dependent on age and gender [46,47], which in part was also applicable in our cohort, prevalence estimation might be more accurate using those age-and gender-adjusted cut-off values and the estimated prevalence of 75% via MFI seems to be more precise. This is in line with the previously reported prevalence of fatigue of 81-100% in spinobulbar muscular atrophy (SBMA) and SMA patients assessed via FSS and PedsQL™ Multidimensional Fatigue Scale [24,25]. Regarding the development in fatigue over the course of 14 months, both instruments depict a similar relative change for general fatigue, which indicates their suitability to measure the same construct in the long term.…”

“…In SMA, fatigue was described early [22] and, from our clinical experience, is a frequent and burdening symptom. Surprisingly, there is little and sometimes even contradicting information on prevalence of and factors associated with fatigue in SMA [23][24][25]. Studies focusing on the several dimensions of fatigue and its impact on SMA patients, particularly in adults, are lacking.…”

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

“…Three of the 19 studies found an association between less severe physical limitations, for example ambulation, and more emotional distress [105,111,113]. Perceptions of fatigue were universal and not associated with physical function, health related quality of life or fatigability in another study [115]. For adults with poorer physical function, engagement with a patients' association was associated with greater psychosocial wellbeing [114].…”

Nusinersen: Evidence of sustained clinical improvement and lessened fatigue in older ambulatory patients with spinal muscular atrophy

“…The observation that fatigue did not worsen with prolonged nusinersen treatment provides encouraging evidence that this therapy offers sustained benefit to older patients with SMA. Patient‐reported fatigue is extremely common (if not universal) for patients with SMA, so this measure is highly relevant to patients as an outcome measure.…”