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Previous Volume 338:278-285 January 29, 1998 Number 5 Next

	Full Text PDF Editorial by Waxman, S. G. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis.

Methods Brain tissue was obtained at autopsy from 11 patients with multiple sclerosis and 4 subjects without brain disease. Fourteen active multiple-sclerosis lesions, 33 chronic active lesions, and samples of normal-appearing white matter were examined for demyelination, inflammation, and axonal pathologic changes by immunohistochemistry and confocal microscopy. Axonal transection, identified by the presence of terminal axonal ovoids, was detected in all 47 lesions and quantified in 18 lesions.

Results Transected axons were a consistent feature of the lesions of multiple sclerosis, and their frequency was related to the degree of inflammation within the lesion. The number of transected axons per cubic millimeter of tissue averaged 11,236 in active lesions, 3138 at the hypocellular edges of chronic active lesions, 875 in the hypocellular centers of chronic active lesions, and less than 1 in normal-appearing white matter from the control brains.

Conclusions Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.

Source Information

From the Departments of Neurosciences (B.D.T., J.P., R.M.R., R.R., L.B.) and Neurology (R.M.R., R.R.), Lerner Research Institute, and the Mellen Center for Multiple Sclerosis Research (R.M.R., R.R.), Cleveland Clinic Foundation, Cleveland; and the Department of Pathology, Haukeland Hospital, Bergen, Norway (S.M.).

Address reprint requests to Dr. Trapp at the Department of Neurosciences, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195.

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