Hypothalamic Dysfunction and Multiple Sclerosis: Implications for Fatigue and Weight Dysregulation

Kevin G. Burfeind, Vijayshree Yadav, Daniel L. Marks

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


Signs and symptoms of multiple sclerosis are usually attributed to demyelinating lesions in the spinal cord or cerebral cortex. The hypothalamus is a region that is often overlooked yet controls many important homeostatic functions, including those that are perturbed in multiple sclerosis. In this review we discuss how hypothalamic dysfunction may contribute to signs and symptoms in people with multiple sclerosis. While dysfunction of the hypothalamic-pituitary-adrenal axis is common in multiple sclerosis, the effects and mechanisms of this dysfunction are not well understood. We discuss three hypothalamic mechanisms of fatigue in multiple sclerosis: (1) general hypothalamic-pituitary-adrenal axis hyperactivity, (2) disordered orexin neurotransmission, (3) abnormal cortisol secretion. We then review potential mechanisms of weight dysregulation caused by hypothalamic dysfunction. Lastly, we propose future studies and therapeutics to better understand and treat hypothalamic dysfunction in multiple sclerosis. Hypothalamic dysfunction appears to be common in multiple sclerosis, yet current studies are underpowered and contradictory. Future studies should contain larger sample sizes and standardize hormone and neuropeptide measurements.

Original languageEnglish (US)
Article number98
JournalCurrent neurology and neuroscience reports
Issue number11
StatePublished - Nov 1 2016


  • Fatigue
  • Hypothalamus
  • Multiple sclerosis
  • Neuroendocrinology
  • Weight dysregulation

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology


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