Abstract & Commentary
Source: Barnett MH, JW Prineas. Relapsing and Remitting Multiple Sclerosis: Pathology of the Newly Forming Lesion. Ann Neurol. 2004;55:458-468.
Barnett and Prineas describe the pathological and clinical findings in 12 patients with relapsing-remitting multiple sclerosis (RRMS), who died shortly after the onset of a relapse. In their evaluation of acute symptomatic lesions, they documented pathological changes not previously associated with new lesion formation, namely, extensive oligodendrocyte apoptosis and microglial activation in 7 patients. In such acute cases there was thought to be rather minor inflammatory lymphocytic infiltration and myelin phagocytosis. Barnett et al conclude that a novel process may be at work in acute MS lesions, whereby oligodendrocyte cell death precedes a secondary inflammatory reaction, and that current laboratory models of MS disease pathogenesis, particularly experimental allergic encephalomyelitis, are inadequate.
Commentary
We know that MS is both clinically and pathologically a heterogenous and complex disease, as recently characterized in a large autopsy and biopsy series of 73 MS cases by Lucchinetti and colleagues (Luchinetti C, et al. Ann Neurol. 2000;47:707-717). Indeed, other investigators have noted the presence of cell death markers on oligodendrocytes in MS, although without undergoing actual apoptosis (Bonetti B, CS Raine. Ann Neurol. 1997;42:74-84). Barnett and Prineas identified apoptotic cells by the finding of condensed nuclear chromatin, although other standard biomarkers such as tunnel staining or activated caspase-3 were not present. While the cell death pathways preceding apoptosis are unclear from this and other studies, Barnett and Prineas hypothesize that this initiates activated complement formation and subsequent leukocyte infiltration in MS lesions. The theory of T cell-mediated myelin destruction as the primary etiology in the immunopathogenesis of MS has yet to be satisfactorily established, and the above work raises a plausible scenario of tissue destruction that needs to be further addressed in future studies. — Brian R. Apatoff
Dr. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.
Barnett and Prineas describe the pathological and clinical findings in 12 patients with relapsing-remitting multiple sclerosis, who died shortly after the onset of a relapse.
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