Abnormal Muscle Energy Metabolism May Be Associated With Enterovirus Infection in Some Chronic Fatigue Syndrome Patients

By Mindy Hung

Oct. 31, 2003 — There is a possible correlation between abnormal lactate response to exercise and the presence of enterovirus sequences in the muscles of a subset of chronic fatigue syndrome (CFS) patients, according to results of a study published in the October issue of the Journal of Neurology, Neurosurgery & Psychiatry.

“While no association between presumptive viral symptoms and chronic fatigue could be established in one large prospective primary care study, chronic fatigue has been found to follow certain specific laboratory confirmed infections, including infectious mononucleosis, viral hepatitis, Coxiella burnetii (Q fever), and parvovirus B19,” write Russell J Lane, MD, FRCP, and colleagues from Imperial College, London, U.K.

All patients referred to Dr. Lane between 1988 and 1998 with significant complaints of CFS and myalgia underwent a subanaerobic threshold exercise test (SATET) and needle muscle biopsy from the left quadriceps. Investigators took samples for venous plasma lactate measurements immediately before and after exercise and at 30 minutes postexercise.

Investigators selected at random 48 biopsies (26 men, 22 women) that fulfilled the Oxford criteria for the diagnosis of CFS for detection of enteroviral RNA by reverse transcription, nested polymerase chain reaction (RT-NPCR). The biopsies were compared using RT-PCR with 29 normal muscle samples.

An abnormal result (SATET+) was defined as a plasma lactate exceeding the previously established upper 99% confidence limit for normal sedentary subjects at two or more time points.

Of the 48 CFS patients, 28 (58.3%) were SATET+, with venous plasma lactate levels exceeding the control upper 99% confidence intervals at two or more time points and the remaining patients had normal responses (SATET-).

Biopsy samples from 10 of the 48 CFS patients were positive for enterovirus (20.8%), and 9 of the 10 cases were among the 28 SATET+ patients (32.1%). Only 1 (5%) of the 20 SATET- patient biopsies was enterovirus positive. PCR products had the greatest homology with coxsackie B virus.

Investigators acknowledge that the effects of “disuse” and lack of fitness in the CFS patients studied cannot be excluded.

Lane and colleagues write, “It must be emphasized that the CFS patients examined in this study may not be representative of the CFS patient population. Many were referred because of prominent muscle symptoms, requiring exclusion of specific neuromuscular diseases.

“However, the observations presented here support the view that CFS is heterogeneous, and that some cases have a peripheral component to their fatigue related to muscle dysfunction,” they add.

The Chronic Fatigue Syndrome Research Foundation provided some funding for the research.

In a related editorial, Marinos C. Dalakas, MD, from the National Institutes of Health, notes that the evidence to support the fact that enteroviruses infect human muscle and cause persistent infection that affects only the metabolic machinery of the cells without muscle destruction seems weak.

“In the past, such findings have turned out to be epiphenomena because enteroviruses are ubiquitous in humans and technical flaws inherently connected to contamination in laboratories working with these viruses are inevitable,” he notes.

Dr. Dalakas adds, “Lane et al have performed a careful study and their findings deserve attention because, if proved to be specific, they will provide the first indirect indication of a viral-related fatigue in a subset of CFS patients.”

J Neurol Neurosurg Psychiatry. 2003;74:1382-1386, 1361-1362

Reviewed by Gary D. Vogin, MD

Source: Medscape Rheumatology MedPulse. Online at: www.medscape.com/rheumatologyhome.

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