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Widespread nerve fiber damage in brains of patients with multiple sclerosis associated with fatigue

The JAMA Network Journals

CHICAGO - Extensive nerve fiber damage in the brains of patients with multiple sclerosis (MS) is associated with the debilitating fatigue associated with the disease, according to an article in the February issue of The Archives of Neurology, one of the JAMA/Archives journals.

MS is a chronic disease of the central nervous system (which includes the brain and spinal cord) characterized by abnormal sensation, tremors, slurred speech, difficulty walking and moving, pain and sometimes blindness. Fatigue affects up to 87 percent of patients with MS and is a major reason why many MS sufferers remain unemployed, according to the article. Although the biological causes of fatigue are unknown, some scientists believe the widespread axonal (nerve fiber) damage associated with MS may also be the root cause of the fatigue reported by patients with MS.

Maria Carmela Tartaglia, B.Sc., M.D., of Montreal Neurological Institute and Hospital, Quebec, and colleagues examined the relationship between nerve fiber damage in the brains of patients with MS and fatigue. Based on their responses to a questionnaire on fatigue, patients were divided into two fatigue groups: low-fatigue (n=26), and high-fatigue (n=34). Using magnetic resonance spectroscopy, the researchers measured the N-acetylaspartate/creatine ratio (NAA/Cr, the ratio between these two naturally occurring brain chemicals is an indicator of proper nerve functioning, and a higher NAA/Cr ratio indicates better nerve functioning) in the brains of patients with MS.

The researchers found that the NAA/Cr ratio was significantly lower in the brains of patients in the high-fatigue group, indicating more nerve fiber damage and poorer nerve functioning.

"Our observations, combined with those of others, suggest that widespread axonal dysfunction is associated with fatigue in MS," the authors write. "It may be hypothesized that diffuse white matter [brain] disease translates into an increase in the central nervous system effort required by a patient with MS to perform the same activity as compared with a disease-free subject, with resultant fatigue."

(Arch Neurol. 2004;61:201-207. Available post-embargo at

Editor's Note: This study was supported by grants from the Medical Research Council of Canada, Ottawa, Ontario, and the MS Society of Canada, Toronto, Ontario.

Editorial: Fatigue in Multiple Sclerosis

In an accompanying editorial, Michael K. Racke, M.D., of the University of Texas Southwestern Medical Center, Dallas, and colleagues write, "Although several therapies have shown some promise in the treatment of fatigue in patients with MS, the lack of a truly effective treatment for this symptom may be due to the underlying pathophysiology for MS still being debated."

Dr. Racke and colleagues write that the findings of Tartaglia et al contribute to an understanding of fatigue in patients with MS by suggesting that the underlying problem may be the nerve damage itself. "The implication of this finding is that rather than trying to explain fatigue solely on the basis of conduction block [poor conduction of nerve impulses] or inflammatory mediators, axonal injury may be an important contributor to the development of MS fatigue," write the editorialists.


(Arch Neurol. 2004;61:176-177. Available post-embargo at

Editor's Note: This study was supported by grants (Drs. Racke and Frohman) from the National Multiple Sclerosis Society, New York, N.Y.; the Yellow Rose Foundation, Dallas, Tex. (Drs. Racke and Frohman), and grants from the National Institutes of Health, Bethesda, Md. (Dr. Racke).

For more information, contact JAMA/Archives Media Relations at 312-464-JAMA (5262) or e-mail .

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