Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate
Article first published online: 2 OCT 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 3, pages 385–394, September 2012
How to Cite
Brück, W., Popescu, B., Lucchinetti, C. F., Markovic-Plese, S., Gold, R., Thal, D. R. and Metz, I. (2012), Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate. Ann Neurol., 72: 385–394. doi: 10.1002/ana.23621
- Issue published online: 2 OCT 2012
- Article first published online: 2 OCT 2012
- Accepted manuscript online: 14 APR 2012 08:27AM EST
- Manuscript Accepted: 9 APR 2012
- Manuscript Revised: 21 MAR 2012
- Manuscript Received: 17 JAN 2012
Neuromyelitis optica (NMO) and multiple sclerosis (MS) are considered inflammatory demyelinating diseases with distinguishing pathological characteristics. NMO pathology shows perivascular immunoglobulin G and complement deposition, as well as an astrocytopathy with aquaporin-4 (AQP4) loss. MS lesions reveal a profound, interindividual heterogeneity in immunopathological patterns of active demyelination, which has been challenged by the description of stage-dependent sequences of pathological features. The aim of our study was to compare the histological characteristics of early active demyelinating NMO and MS brain lesions.
Thirteen cases with supraspinal active demyelinating NMO lesions were analyzed using immunohistochemistry. Results were compared with the published characteristics of MS lesions.
A subset of supraspinal lesions from AQP4-IgG-seropositive NMO patients revealed both (1) complement activation products within macrophages at sites of active demyelination and (2) oligodendrocyte apoptosis and a preferential loss of myelin-associated glycoprotein. These characteristics resemble features previously associated with MS lesion patterns II and III, and were present in addition to characteristic histopathological NMO features, namely loss of AQP4 and astrocytes.
Early active demyelinating NMO lesions may show complement within macrophages and oligodendrocyte apoptosis associated with a selective loss of minor myelin proteins, in addition to typical NMO features. We hypothesize these findings occur simultaneously only in a subset of active demyelinating NMO lesions. These observations plausibly explain the findings of Barnett and Prineas and further support the concept of interindividual heterogeneity in MS. ANN NEUROL 2012;72:385–394.