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Axonal loss in normal-appearing white matter in a patient with acute MS

From the Department of Neurosciences, Lerner Research Institute (Drs. Bjartmar, Kidd, Rudick, and Trapp), Department of Neurology (Mellen Center) (Drs. Kinkel and Rudick), and the Center for Clinical Research (Dr. Rudick), Cleveland Clinic Foundation, OH.

Address correspondence and reprint requests to Dr. Bruce D. Trapp, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: trappb{at}ccf.org

Background: Brain imaging studies detect abnormalities in normal-appearing white matter in patients with MS. Objective: To investigate the histopathologic basis for these changes in autopsy tissue from a patient with MS with 9 months’ disease duration and a terminal brain stem lesion. Methods: The brain stem and spinal cord were analyzed ultrastructurally and immunocytochemically for axons, myelin, and activated microglia/macrophages. Results: Pathologic findings were consistent with a terminal inflammatory demyelinated lesion at the cervicomedullary junction. The ventral spinal cord column, containing descending tracts, exhibited 22% axonal loss at segment C7, but grossly normal immunostaining for myelin. Confocal and electron microscopy revealed myelin sheaths without axonal content and initial stages of myelin degradation by activated microglia/macrophages among intact myelinated axons. Axonal number and appearance was normal in ascending sensory tracts. Conclusions: These studies confirm axonal degeneration in the absence of myelin loss as one histopathologic correlate to abnormal MR findings in patients with MS.

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