In search of distinct MS-related fatigue subtypes: results from a multi-cohort analysis in 1.403 MS patients

  • Gesa E. A. Pust
  • Jana Pöttgen
  • Jennifer Randerath
  • Stephanie Lau
  • Christoph Heesen
  • Stefan M. Gold
  • Iris-Katharina PennerEmail author
Original Communication


Fatigue is among the most disabling symptoms in patients with multiple sclerosis (PwMS). The common distinction between cognitive and motor fatigue is typically incorporated in self-rating instruments, such as the Chalder Fatigue Questionnaire (CFQ), the Fatigue Scale for Motor and Cognitive Functions (FSMC) or the Modified Fatigue Impact Scale (MFIS). The present study investigated the factor structure of the CFQ, the FSMC and the MFIS utilizing exploratory (EFA) and confirmatory factor analysis (CFA) as well as exploratory structural equation modeling (ESEM). Data of 1.403 PwMS were analyzed, utilizing four samples. The first sample (N = 605) was assessed online and split into two stratified halves to perform EFA, CFA, and ESEM on the CFQ and FSMC. The second sample (N = 293) was another online sample. It served to calculate CFA and ESEM on the CFQ and FSMC. The third sample was gathered in a clinical setting (N = 196) and analyzed by applying CFA and ESEM to the FSMC. The fourth sample (N = 309) was assessed in a clinical setting and allowed to run a CFA and ESEM on the MFIS. Proposed factor structures of all questionnaires were largely confirmed in EFA. However, none of the calculated CFAs and ESEMs could verify the proposed factor structures of the three measures, even with oblique rotation techniques. The findings might have implications for future research into the pathophysiological basis of MS-related fatigue and could affect the suitability of such measures as outcomes for treatment trials, presumably targeting specific sub-components of fatigue.


Fatigue Assessment Validation Multiple sclerosis 



We thank Lena Katharina Feddersen for support with data collection.

Compliance with ethical standards

Conflicts of interest

GEAP received speaker honoraria and project funding from Genzyme Sanofi. CH received speaker honoraria and project funding from Genzyme Sanofi, Roche, Merck, Biogen. SMG reports honoraria from Mylan GmbH, Almirall S. A. and Celgene and research grants from Biogen. IKP has received honoraria for speaking at scientific meetings, serving at scientific advisory boards and consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, Celgene, Desitin, Genzyme, Merck, Novartis, Roche, and Teva. She has received research support from Teva, Novartis and the German MS Society. All remaining authors have no conflict of interest to declare.

Ethical standards

All studies were conducted in accordance with the 1964 Declaration of Helsinki and its later amendments and received ethical clearance.

Informed consent

All persons provided written informed consent prior to their inclusion in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie Hamburg (ZMNH)Universitätsklinikum Hamburg EppendorfHamburgGermany
  2. 2.Department of PsychologyUniversity of KonstanzConstanceGermany
  3. 3.Lurija Institute for Rehabilitation and Health Sciences at the University of KonstanzSchmieder Foundation for Sciences and ResearchAllensbachGermany
  4. 4.Klinik und Poliklinik für NeurologieUniversitätsklinikum Hamburg-Eppendorf (UKE)HamburgGermany
  5. 5.Charité Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin FranklinBerlinGermany
  6. 6.Charité Universitätsmedizin Berlin, Medizinische Klinik m.S. Psychosomatik, Campus Benjamin FranklinBerlinGermany
  7. 7.Department of Neurology, Medical FacultyHeinrich Heine University DüsseldorfDüsseldorfGermany
  8. 8.COGITO Center for Applied Neurocognition and Neuropsychological ResearchDüsseldorfGermany

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