Uhthoff's phenomena in MS - Clinical features and pathophysiology

Teresa C. Frohman, Scott L. Davis, Shin C Beh, Benjamin Greenberg, Gina Remington, Elliot Frohman

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations


In the late 19th century, Wilhelm Uhthoff reported on a series of patients with acute optic neuritis who manifested similar recurrent, stereotyped visual symptoms that were of paroxysmal onset, short in duration, and reversible. These 'Uhthoff's phenomena', which are a feature of multiple sclerosis (MS) and other demyelinating diseases, can be triggered by factors including the perimenstrual period, exercise, infection, fever, exposure to high ambient temperatures, and psychological stress. Here, we characterize the clinical, pathophysiological and neurotherapeutic challenges associated with Uhthoff's phenomena, and discuss the differentiation of these events from other paroxysmal, acute or subacute changes in functional capabilities and neurological symptoms in MS. For instance, whereas MS exacerbations are contingent on immune dysregulation, Uhthoff's phenomena are predicated on ion channel modifications, in conjunction with thermoregulatory derangements that transiently alter the conduction properties of demyelinated axons. An understanding of these pathophysiological underpinnings of Uhthoff's phenomena is germane to their recognition and timely treatment.

Original languageEnglish (US)
Pages (from-to)535-540
Number of pages6
JournalNature Reviews Neurology
Issue number9
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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