Background Multiple sclerosis is an inflammatory demyelinatingdisease of the central nervous system and is the most commoncause of neurologic disability in young adults. Despite antiinflammatoryor immunosuppressive therapy, most patients have progressiveneurologic deterioration that may reflect axonal loss. We conductedpathological studies of brain tissues to define the changesin axons in patients with multiple sclerosis.
Methods Brain tissue was obtained at autopsy from 11 patientswith multiple sclerosis and 4 subjects without brain disease.Fourteen active multiple-sclerosis lesions, 33 chronic activelesions, and samples of normal-appearing white matter were examinedfor demyelination, inflammation, and axonal pathologic changesby immunohistochemistry and confocal microscopy. Axonal transection,identified by the presence of terminal axonal ovoids, was detectedin all 47 lesions and quantified in 18 lesions.
Results Transected axons were a consistent feature of the lesionsof multiple sclerosis, and their frequency was related to thedegree of inflammation within the lesion. The number of transectedaxons per cubic millimeter of tissue averaged 11,236 in activelesions, 3138 at the hypocellular edges of chronic active lesions,875 in the hypocellular centers of chronic active lesions, andless than 1 in normal-appearing white matter from the controlbrains.
Conclusions Transected axons are common in the lesions of multiplesclerosis, and axonal transection may be the pathologic correlateof 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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