Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions

Oligodendrocyte and axon pathology was studied in 11 autopsy cases of clinically silent multiple sclerosis. A total of 54 lesions, either demyelinated or late remyelinated, were distributed through the whole brain and spinal cord with 39% of the lesions located in periventricular areas. Determination of axon density revealed an average reduction of 64% and 59% in demyelinated and remyelinated lesions with an extreme variation between different plaques and cases. Oligodendrocytes were identified by immunocytochemistry for myelin oligodendrocyte glycoprotein (MOG) and in situ hybridization for proteolipid protein (PLP) mRNA. Oligodendrocytes were almost completely lost in demyelinated lesions; remyelinated lesions revealed preservation of a considerable number of oligodendrocytes within the lesions. At the border between plaques and the periplaque white matter, similar oligodendrocyte numbers as in remyelinated lesions were found. Different factors including lesion site, axonal preservation and remyelination may thus contribute to the clinical nonappearance of multiple sclerosis lesions.