May 4, 2004
Mark S. Freedman, MD
Medscape Neurology & Neurosurgery
My question relates to hypothalamic effects of multiple sclerosis (MS). A 46-year-old patient of mine had been diagnosed with primary progressive MS for over 18 years. She recently died secondary to complications of MS. Before she died, she was receiving triple antibiotic therapy for aspiration pneumonia. Despite negative blood cultures, she continued to spike temperatures up to 104 °F on a circadian rhythm. Also of note, her sodium level went up to 163 and her blood urea nitrogen (BUN) went from 14 to 83. What might explain this?
Brian Bonte, DO
Response from Mark S. Freedman, MD
Professor of Neurology, University of Ottawa, Canada, and Director, Multiple Sclerosis Clinic, Ottawa Hospital, Canada.
Hypothalamic involvement is not uncommon in MS, and on the basis of a recent postmortem investigation, it is often not a good prognostic sign. Typically, a dysregulation of temperature results in hypo- rather than hyperthermia. In fact, I have a patient who experiences a drop in temperature of many degrees when her MS flares. On one occasion when she was brought into the emergency room, the triage team thought she was deceased because she was so cold! Usually, she's admitted to intensive care, placed in the same sort of warming suits used for severe hypothermia, and treated with steroids, and after a few days her temperature comes back under control. This is not unlike a case described and heavily investigated by another group.
The other abnormalities described in the case in question raise other concerns. For example, her fever and intercurrent pneumonia may well be responsible for excessive, insensible water loss through hyperventilation causing dehydration, which would explain the elevated sodium and BUN levels. With the way this question was posed, it would seem that you did not believe her spiking temperatures and electrolyte changes were due to an infection but, rather, primary hypothalamic dysfunction.
MS is not a typical cause of "fever of unknown origin." Although the hypothalamic-pituitary axis is well known to be disturbed in MS, usually this involves problems with cortisol secretion. Another long-held theory is that this disorder actually is responsible for the immune abnormalities often observed in MS because of the connections between the sympathetic outflow system and immune organs, such as the spleen. Nevertheless, as shown in the very recent report of the Dutch investigators, the finding of hypothalamic lesions in MS is often associated with a more downhill course of disease that often results in death. Of note, but not unusual, is that many of the patients in this series died of pneumonia.
Mark S. Freedman, BSc, MSc, MD, has disclosed that he has received grants
for clinical research from Serono, Biogen, and Berlex. He has received
grants for educational activities from Serono, Biogen, Teva, and Berlex
and has served as an advisor or consultant for these companies, along with
Bayer and Pfizer. He has received honoraria for speaking from all of the
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