Complexity and heterogeneity in demyelinating disease

Abstract

In 1894, Eugene Devic (1858–1930) described a 45-year-old female hatter in whom ‘l’autopsie revela l’existence d’un foyer de myelite aigue diffuse localisee a la region du renflement lombaire et d’une nevrite optique double bien marquee’ … the autopsy showed a focus of acute diffuse myelitis localized to the lumbar enlargement, as well as a distinct bilateral optic neuritis (Devic, 1894). He called the condition ‘neuromyelite optique aigue’. Subsequently, it has not proved easy to establish the relationship between neuromyelitis optica and multiple sclerosis. Epidemiological studies performed during the second half of the 20th century show clearly that the typical form of demyelinating disease in Africa, Asia, the Far East and Aboriginal populations is neuromyelitis optica or optic-spinal multiple sclerosis. The relapsing-remitting phenotype, affecting many sites within the brain and spinal cord, is relatively uncommon by comparison with these features of multiple sclerosis in northern Europeans. Until recently, criteria for the diagnosis of neuromyelitis optica included: bilateral optic neuritis and acute myelitis with no evidence for clinical disease in other parts; a spinal lesion extending over ≥3 segments on MR imaging and without cerebral lesions; abnormal cerebrospinal fluid with >50 wbc or >5 neutrophils; and the course either monophasic or relapsing and remitting (Wingerchuk et al ., 1999). Meanwhile the neuropathology of human demyelinating disease was undergoing re-evaluation. Neuromyelitis optica is characterized by extensive demyelination with partial necrosis of the spinal cord white and grey matter, acute axonal injury, eosinophil and granulocyte inflammatory infiltrates, deposition of IgG and IgM, and perivascular complement activation (Lucchinetti et al ., 2002). These features mimic those seen in some more typical cases of multiple sclerosis—the so-called pattern II that, alongside cases characterized by predominant T cell and macrophage infiltration (pattern I), hypoxia-like changes (pattern III) or primary damage to oligodendrocytes (pattern IV) supports the …