Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.
OBJECTIVE
Advanced immunopathological techniques hold promise for more precise diagnosis of idiopathic demyelinating diseases of the central nervous system. We review recent progress in differentiating and understanding the disease mechanisms of acute disseminated encephalomyelitis, neuromyelitis optica, and classical multiple sclerosis.


RESULTS
Four distinct immunopathological patterns have been described in multiple sclerosis patients, potentially implicating different inflammatory, demyelinating, and apoptotic mechanisms. A specific serum biomarker, neuromyelitis optica immunoglobulin G, is strongly associated with neuromyelitis optica and identifies patients with severe optic nerve and spinal cord lesions with specific pathological features such as eosinophilic and neutrophilic inflammatory infiltrates, necrosis, vascular hyalinization, and extensive vasculocentric immunoglobulin and complement deposition. This biomarker targets the water channel aquaporin-4, which is lost in neuromyelitis optica lesions. Acute disseminated encephalomyelitis still has no validated clinical diagnostic criteria but its perivenous pathological findings distinguish it from multiple sclerosis and neuromyelitis optica.


CONCLUSIONS
The clinically heterogeneous group of idiopathic inflammatory demyelinating diseases of the central nervous system is characterized by several immunopathological patterns that suggest the involvement of diverse pathogenic effector mechanisms. Future advances in experimental pathology, immunology, molecular genetics, and neuroimaging, as well as the discovery of specific biomarkers, will more precisely define these disorders and lead to better targeted therapies.
Wingerchuk
Dean M
DM
Mayo Clinic College of Medicine, Scottsdale, Arizona 85259, USA. wingerchuk.dean@mayo.edu
Lucchinetti
Claudia F
CF
D051401:Aquaporin 4 / Q000276:immunology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002490:Central Nervous System / Q000276:immunology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D011237:Predictive Value of Tests
D051401:Aquaporin 4; D015415:Biomarkers; D007074:Immunoglobulin G