Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients

Abstract

Brain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal-appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin-related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal-appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.

Baló's concentric sclerosis in a woman from Papua New Guinea

“…3 However, more recently Moore et al have reported a case demonstrating lesions of the Baló type in the lumbar spinal cord as well as in the medulla oblongata 6 and Yao et al have described the histopathological findings of two patients with concurrent typical multiple sclerosis plaques and concentric sclerosis lesions and of another patient with these two lesion types in continuity. 2 The prior episode of left optic neuritis in our patient is consistent with the concept that Baló's concentric sclerosis is a variant of multiple sclerosis. In the present case, the diagnosis of Baló's concentric sclerosis was made on the basis of the second biopsy of the cerebral white matter lesion and supportive MRI findings.…”

“…1,2 Baló suggested that 'encephalitis periaxialis concentrica' might represent a disease entity distinct from multiple sclerosis, partly because of the absence of spinal cord lesions. 3 However, more recently Moore et al have reported a case demonstrating lesions of the Baló type in the lumbar spinal cord as well as in the medulla oblongata 6 and Yao et al have described the histopathological findings of two patients with concurrent typical multiple sclerosis plaques and concentric sclerosis lesions and of another patient with these two lesion types in continuity.…”

“…6 On the other hand, Yao et al found reduced oligodendrocyte numbers and lower levels of messenger RNA for myelin-related proteins in the partially myelinated areas compared with the normal-appearing white matter, and concluded that ongoing myelin breakdown, rather than remyelination of previously demyelinated areas, was responsible for the thin myelin sheaths. 2 It is possible that the concentric alternating banded pattern represents repeated immunemediated attacks against myelin antigens, as there is increasing evidence that multiple sclerosis is an autoimmune disease. 12 Serial MRI has demonstrated that the lesions of multiple sclerosis expand in a centrifugal pattern, 13 but in typical multiple sclerosis there are many smaller lesions rather than a single large rapidly expanding lesion.…”

“…It is characterized by lesions with an unusual concentric pattern of alternating demyelinated and partially myelinated bands in the cerebral white matter. 1,2 In 1928, Baló reported this pattern in lesions found at autopsy in a 23-year-old male with right hemiparesis, aphasia and papilloedema 3 but the first reported case was that described by Marburg in 1906 as 'acute multiple sclerosis'. 4 Concentric sclerosis usually affects young adults and has an acute or subacute onset and progressive course.…”

HLA-DR2–restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice

“…However, our study has revealed that a proportion of Japanese MS patients possess DRB1*1502 but not DRB1*1501, and that TCLs recognizing the DRB1*1501-related MBP or PLP peptides can be efficiently generated from DRB1*1502 + patients (Ohashi et al, unpublished data). Furthermore, DRB1*1502 was found to be present in the vast majority of patients with concentric sclerosis (Baló's disease) (unpublished observation), which is probably a variant form of MS (24). Moreover, DRB1*1501 and DRB1*1502 differ only in the amino acid at position 86 of the DRβ chain (valine in DRB1*1501 and glycine in DRB1*1502) (25).…”