Fatigue as a symptom or comorbidity of neurological diseases

Key Points

  • Fatigue is complex and can occur as a primary or secondary symptom as well as a comorbidity of neurological disease; multiple types can coexist in the same patient

  • Disentangling the origin and nature of fatigue in patients with neurological diseases is challenging and often fails to achieve an unambiguous assignment of fatigue

  • Fatigue can be characterized by standardized self-report questionnaires and fatigability testing, which can help to determine the impact of fatigue on patients' daily life

  • Assessments of fatigue can help to guide pharmacological treatment decision-making even in the absence of convincing evidence-based strategies

  • Nonpharmacological strategies, such as mindfulness-based stress reduction, cooling, yoga, exercise and cognitive rehabilitation, can help to manage fatigue in patients with neurological diseases

Abstract

Fatigue, best described as an overwhelming feeling of tiredness and exhaustion, occurs in the context of various neurological diseases. The high prevalence of fatigue as either a symptom or a comorbidity of neurological disease must be taken seriously, as fatigue interferes with patients' activities of daily living, has a remarkable negative impact on quality of life, and is a major reason for early retirement. The tremendous consequences of fatigue are consistent across neurological diseases, as is the uncertainty concerning its underlying pathophysiological mechanisms. Inconsistencies in defining fatigue contribute to the present situation, in which fatigue represents one of the least-studied and least- understood conditions. Tools for assessing fatigue abound, but few can be recommended for clinical or research use. To make matters worse, evidence-based pharmacological treatment options are scarce. However, non-pharmacological approaches are currently promising and likely to become of increasing importance. In sum, fatigue is challenging for both health-care professionals and patients. The present article aims to provide a comprehensive review of the literature on fatigue in neurological disease, and to reveal its complexity, as well as weaknesses in the concept of fatigue itself.

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Figure 1: Conceptual models, causes and consequences of fatigue in neurological disease.

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Acknowledgements

The authors' work is supported by Deutsche Forschungs-gemeinschaft (grant DFG Exc 257 to F.P.) The authors thank Hanna Zimmermann for her valuable editorial support in preparing the manuscript.

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I.-K.P. and F.P. researched data for the article; contributed substantially to discussions of its content, wrote the manuscript, and undertook review or editing of the manuscript before submission.

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Correspondence to Iris-Katharina Penner.

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The authors declare that I.-K.P. has received honoraria for speaking at scientific meetings, serving on scientific advisory boards and consulting activities from Adamas Pharma, Bayer Pharma, Biogen, Genzyme, Merck Serono, Novartis, Roche, Teva Pharmaceuticals; and that she has received research support from Novartis, the German Multiple Sclerosis Society, and Teva Pharmaceuticals. F.P. declares that he has served on scientific advisory boards for MedImmune and Novartis; received speaker honoraria and travel funding from Alexion, Bayer, Biogen Idec, Chugai, MedImmune, Merck Serono, Novartis, Sanofi-Aventis/Genzyme, Teva Pharmaceuticals, and Shire; is an academic editor of PLoS ONE and an associate editor of Neurology Neuroimmunology & Neuroinflammation; has consulted for Alexion, Biogen Idec, MedImmune, Sanofi-Aventis/Genzyme and Shire; and received research support from Alexion, Arthur Arnstein Stiftung Berlin, Bayer, Biogen Idec, EU FP7 Framework Program, German Ministry of Education and Research, German Research Council, Guthy-Jackson Charitable Foundation, Merck Serono, National Multiple Sclerosis Society of the USA, Novartis, Sanofi-Aventis/Genzyme, Teva Pharmaceuticals, and Werth Stiftung of the City of Cologne.

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Penner, I., Paul, F. Fatigue as a symptom or comorbidity of neurological diseases. Nat Rev Neurol 13, 662–675 (2017). https://doi.org/10.1038/nrneurol.2017.117

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