Reliability and Validity of Self-Report Questionnaires as Indicators of Fatigue in RYR1-Related Disorders

Article type: Research Article

Authors: Kuo, Anna^{a; 1} | Todd, Joshua J.^{a; 1; *} | Witherspoon, Jessica W.^a | Lawal, Tokunbor A.^a | Elliott, Jeffery^a | Chrismer, Irene C.^a | Shelton, Monique O.^a | Razaqyar, Muslima S.^a | Jain, Minal S.^b | Vasavada, Ruhi^b | Waite, Melissa^b | Drinkard, Bart^b | Michael, Darren^c | Richarte, Alicia^c | Bönnemann, Carsten G.^d | Meilleur, Katherine G.^a

Affiliations: [a] Neuromuscular Symptoms Unit, National Institute of Nursing Research (NIH), United States | [b] Mark O Hatfield Clinical Center, National Institutes of Health (NIH), United States | [c] Hyperion Biotechnology Inc., San Antonio TX, United States | [d] Neurogenetics Branch, National Institute of Neurological Disorders and Stroke - NINDS (NIH), United States

Correspondence: [*] Correspondence to: Joshua J. Todd, Neuromuscular Symptoms Unit, National Institute of Nursing Research, National Institutes of Health, 10 Center Drive, Room 2A07, Bethesda MD, USA. Tel.: +1 301 480 4109; E-mail: joshua.todd@nih.gov.

Note: [1] Denoted authors contributed equally to the preparation of this manuscript.

Abstract: Background:RYR1-related disorders (RYR1-RD), are a spectrum of genetic neuromuscular disorders. Affected individuals frequently experience fatigue yet appropriate tools to assess RYR1-RD-associated fatigue remain underdeveloped. Objective:This study assessed the reliability and validity of two self-report questionnaires, the multidimensional fatigue inventory (MFI-20) and adult/pediatric functional assessment of chronic illness-fatigue (FACIT-F/Peds-FACIT-F) as potential fatigue measures in RYR1-RD affected individuals. Methods:Participants (n = 37) were enrolled in an RYR1-RD combined natural history study and clinical trial. At baseline, participants completed fatigue questionnaires, six-minute walk test (6MWT), cardiopulmonary exercise test (CPET) and saliva collection for fatigue biomarker index (FBI) quantification. Results:All questionnaires exhibited good test-retest reliability (n = 18, ICC > 0.80). MFI-20 (n = 37), and FACIT-F (n = 28) also showed good internal consistency (Cronbach’s α> 0.80). All MFI-20 subscales, except mental fatigue, and FACIT-F demonstrated evidence of criterion validity when correlated against percent predicted 6MWT distance (MFI-20 n = 37; r = –0.34 to –0.47, all p < 0.05, mental fatigue, r = –0.16, p = 0.35; FACIT-F n = 28, r = 0.41, p = 0.03). This was not the case for percent predicted VO2 peak (all p > 0.05). FBI correlated with MFI-20 general fatigue dimension only (r = –0.35, p = 0.03). Comparison of standardized questionnaire scores revealed that RYR1-RD affected individuals experience significantly greater fatigue than the general population. Conclusions:MFI-20 and FACIT-F are valid and reliable tools for assessing RYR1-RD-associated fatigue, a symptom centrally implicated in this rare disorder.

Keywords: Fatigue, myopathy, RYR1, quality of life, ryanodine receptor

DOI: 10.3233/JND-180335

Journal: Journal of Neuromuscular Diseases, vol. 6, no. 1, pp. 133-141, 2019