Current perspectives on the diagnosis and management of fatigue in multiple sclerosis

ABSTRACT

Introduction

Fatigue is a common and debilitating symptom among multiple sclerosis (MS) patients with a prevalence up to 81% and with a considerable impact on quality of life. However, its subjective nature makes it difficult to define and quantify in clinical practice. Research aimed at a more precise definition and knowledge of this construct is thus continuously growing.

Areas covered

This review summarizes the most relevant updates available on PubMed up to 1 July 2022 regarding: the assessment methods that aim to measure the concept of fatigue (as opposed to fatigability), the possible treatment pathways currently available to clinicians, interconnection with the pathophysiological substrates and with the common comorbidities of MS, such as depression and mood disorders.

Expert opinion

The in-depth study of fatigue can help to better understand its actual impact on MS patients and can stimulate clinicians toward a more valid approach, through a targeted analysis of this symptom. Considering fatigue from a multidimensional perspective allows the use of patient-tailored methods for its identification and subsequent treatment by different professional figures. Better identification of methods and treatment pathways would reduce the extremely negative impact of fatigue on MS patients’ quality of life.

KEYWORDS:

• Fatigue
• fatigability
• multiple sclerosis
• assessment
• pathophysiology
• fatigue treatment

Article highlights

• Fatigue, a subjective feeling of tiredness and exhaustion at rest, is a relevant symptom in multiple sclerosis (MS) patients, significantly impacting their quality of life.

• Fatigue should be distinguished from the construct of fatigability, the latter being the objectively measurable performance decline after the administration of a tiring cognitive or physical task.

• Due to the subjective nature of fatigue, it is difficult for clinicians and researchers to collect standardized and quantitative data. Different questionnaires and scales are currently available in clinical and research practice, the most used in MS are the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), whose cut-offs are useful to distinguish fatigued from non-fatigued patients.

• The exact cause of fatigue in MS is still unclear and the literature trying to unveil its pathophysiological substrates is continuously growing. Convergent pieces of evidence support the theory of a dysfunction of thalamo-striato-cortical circuits and structural disconnection of their grey matter regions as possible substrates.

• Fatigue often co-occurs with other MS symptoms and comorbidities: secondary fatigue is notably difficult to disentangle from mood disorders, cognitive deficits, sleep disorders and disease-modifying treatment side effects.

• The burdensome nature of fatigue for MS patients highlights the need for tailored treatments: both pharmacological and non-pharmacological approaches have been developed. Drug-free treatments, involving different professional figures, are currently considered the best strategy for the reduction of fatigue in MS patients.

Declaration of interests

M Filippi is Editor-in-Chief of the Journal of Neurology and Associate Editor of Radiology, Human Brain Mapping and Neurological Sciences; received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries; and receives research support from Almiral, Biogen Idec, Eli Lilly, Merck-Serono, Novartis, Roche, Sanofi, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). MA Rocca received speaker honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva; and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.