Feb. 18, 2004
Laurie Barclay, MD
Medscape Medical News
Diffuse axonal damage underlies the symptom of fatigue in patients with multiple sclerosis (MS), according to the results of a study published in the February issue of the Archives of Neurology.
"Our observations, combined with those of others, suggest that widespread axonal dysfunction is associated with fatigue in MS," write Maria Carmela Tartaglia, BSc, MD, from Montreal Neurological Institute and Hospital in Quebec, Canada, and colleagues. "It may be hypothesized that diffuse white matter 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."
Based on their responses to the Fatigue Severity Scale questionnaire, 73 patients with MS were divided into a low-fatigue group (n = 26 patients) and a high-fatigue group (n = 34 patients). Brain N-acetylaspartate/creatine (NAA/Cr) ratio, an indicator of more normal nerve functioning, was measured using magnetic resonance spectroscopy.
Compared with the low-fatigue group, the high-fatigue group had a significantly lower brain NAA/Cr ratio (P = .003). The NAA/Cr ratio was directly correlated with Fatigue Severity Scale Scores (P = .02), disease duration, and T2 lesion volume. Because of the known sensitivity of NAA levels to demyelinating injury, the authors attribute the lower NAA/Cr ratio to a lower NAA and not to a higher Cr.
"Fatigue has a tremendous effect on the activities of daily living for patients with MS; it interferes with work, family life, and social activities," the authors write. "The results of this study imply that neuroprotective agents that would serve to halt or delay axonal injury may be beneficial in postponing the development of fatigue."
The Medical Research Council of Canada and the MS Society of Canada, both in Toronto, Ontario, supported this study.
In an accompanying editorial, Michael K. Racke, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues suggest that the underlying problem explaining fatigue in patients with MS may be the diffuse axonal damage itself.
"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," they write. "The implication of this finding is that rather than trying to explain fatigue solely on the basis of conduction block, axonal injury may be an important contributor to the development of MS fatigue."
The National Multiple Sclerosis Society, the Yellow Rose Foundation, and the National Institutes of Health supported this work.
Arch Neurol. 2004;61:176-177, 201-207
Reviewed by Gary D. Vogin, MD
Copyright © 2004, Medscape