Lesions of Baló's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Baló-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1alpha and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.

Six sporadic cases of dementia with lobar atrophy and neuronal cytoplasmic inclusions (Pick's disease) could be separated into two groups on the basis of the involvement of subcortical structures, the distribution and the histochemical, immunochemical, and ultrastructural characteristics of the inclusions, and possibly the age at onset. The first group (classic) was characterized by predominantly cortical atrophy and the presence in the hippocampus and neocortex of argyrophilic cytoplasmic inclusion bodies that reacted with a monoclonal antibody against neurofilament proteins and antitubulin antisera. Ultrastructurally the bodies were composed of straight fibrils of variable diameter, averaging 15 nm, and long-period constricted fibrils. The second group (generalized) showed subcortical as well as antibodies against neurofilaments and microtubules. Ultrastructurally the straight fibrils composing the bodies were coated with granular material, presumed to be derived from ribosomes. The generalized cases occurred in younger patients than did the classic cases in this series.

The process of remyelination in the superior cerebellar peduncles of mice following demyelination with Cuprizone was studied immunohistochemically using antisera to myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). Demyelination occurred after formation of myelinic vacuoles and resulted in almost complete loss of demonstrable MBP and MAG from the peduncle. Prior to the onset of remyelination, oligodendrocytes with cytoplasmic staining for both proteins appeared in the peduncle. These cells were then associated with remyelinating axons. The axons were remyelinated in clusters until the MBP and the MAG in the whole peduncle were reconstituted, although the axon sheaths were thinner than those in normal animals. The results show that the immunohistochemical distribution of MBP and MAG in remyelinating axons resembles that in normal axons, and that the expression of myelin proteins in oligodendrocytes during remyelination reverts to that seen during normal development.

The clinical and pathological features of two unrelated sporadic cases of neuroaxonal dystrophy occurring in young adults are described. Initial clinical manifestations in both patients were those of primary psychiatric disorders. They subsequently developed extrapyramidal symptoms, dementia, cerebellar ataxia, and corticospinal dysfunction, but neither demonstrated myoclonic seizures. In one patient the diagnosis was made before death by brain biopsy. On pathological examination both patients showed a generalized distribution of spheroids within the central nervous system and, in one, in the peripheral nerves. In both patients, Lewy bodies were demonstrated in the pigmented brainstem nuclei. In addition, one patient showed ultrastructurally verified Lewy bodies in the cerebral cortex. Although these two cases could be considered examples of juvenile neuroaxonal dystrophy, we prefer to regard them as transitional forms in a disease spectrum with classic infantile neuroaxonal dystrophy and Hallervorden-Spatz disease at the two extremes.