Biological correlates of post-stroke fatigue: a systematic review

Acta Neurol Scand. 2012 Apr;125(4):219-27. doi: 10.1111/j.1600-0404.2011.01618.x. Epub 2011 Nov 10.


Fatigue is a common and disabling consequence of stroke. Its mechanisms are unknown. Neuroanatomical abnormalities (e.g. white matter lesions, brain atrophy), neuroendocrine dysregulation, neurotransmitter changes and inflammation are associated with fatigue in conditions other than stroke. This review sought to identify published studies describing associations between post-stroke fatigue and these biological factors. We searched Medline, EMBASE, CINAHL, PsycINFO and AMED on October 15 and PubMed on 28 December 2010 and included studies in English that recruited at least 10 patients (>18 years old) with stroke, assessed fatigue and reported its relationship with neuroanatomical abnormalities, hypothalamo-pituitary-adrenal axis dysregulation, neurotransmitter changes or inflammation. Of 4916 citations from the searches, 17 studies met our inclusion criteria. There was no association between white matter lesions, brain atrophy or pathological type of stroke and fatigue (seven studies, n = 4746). The data on relationship between lesion location and fatigue were inconclusive: four (n = 675) of 13 studies (n = 1613) showed associations between fatigue and infratentorial lesion location (brainstem in particular) or basal ganglia stroke. One study reported C-reactive protein levels and found an association with fatigue. No studies reported hypothalamo-pituitary-adrenal axis dysregulation or neurotransmitter changes and fatigue. We could not perform meta-analysis because the studies used different methods of fatigue assessment, examined different populations and had different designs. The biological mechanisms of post-stroke fatigue are uncertain. Further studies are required to determine the relationship between post-stroke fatigue and biological factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Factors / analysis
  • Brain / pathology
  • C-Reactive Protein / metabolism
  • Fatigue / etiology*
  • Fatigue / metabolism
  • Fatigue / pathology
  • Humans
  • Middle Aged
  • Neurotransmitter Agents / metabolism
  • Stroke / complications*
  • Young Adult


  • Biological Factors
  • Neurotransmitter Agents
  • C-Reactive Protein