MS and NMO: partners no more.

M ultiple sclerosis (MS) and neuromyelitis optica (NMO) are recurring inflammatory disorders of the central nervous system. Although the exact pathogenesis of MS and NMO is uncertain, an autoimmune process directed at glial antigens appears to be a key ingredient. Several lines of evidence support that these 2 entities are separate but closely allied disorders. Some inflammatory lesions associated with MS are composed of macrophages, T cells, B cells, and microglial cells (1, 2). In a number of patients, the pathology appears to be antibody and complement driven, resulting in demyelination and axonal injury (1). Whereas MS may have myelin as its primary target, the immune response in NMO appears to be directed against the astrocyte (3, 4). The pathology of NMO is characterized by necrotizing injury, neutrophils, hyalinized blood vessels, and antibodies that fix complement and are directed against aquaporin 4 (AQP4), a dominant water channel densely expressed on astrocyte foot processes (3,4). In this issue of the Journal, we have 4 articles that attempt to separate further the clinical and diagnostic features of NMO and MS (5–8). Morrow and Wingerchuk (5) provide a wonderful stateof-the-art review of NMO, Kezuka et al (6) show that the presence of the NMO and myelin oligodendrocyte glycoprotein (MOG) antibodies may help predict visual outcome, and Fernandes et al (7) find that the visual fields of patients with NMO rarely return to normal compared to those patients with typical optic neuritis. Finally, Romero et al (8) report a patient with homonymous hemimacular thinning noted on optic coherence tomography as a manifestation of optic tract injury in NMO. The findings of Fernandes et al (7) show that visual field abnormalities are worse in NMO patients following a single episode of optic neuritis. The authors found that only 5% of patient eyes with NMO regained a normal visual field after an attack of optic neuritis compared with nearly 50% who had typical optic neuritis. These findings supplement the long-standing data that visual acuity is worse in NMO and it is consistent with the observation that there is more profound retinal nerve fiber layer loss in this disorder when compared with MS (9). It is disheartening that over a 10-year time frame, 50%– 60% of patients with NMO will be legally blind in one eye as opposed to the routine optic neuritis patient who has a risk of legal blindness in the 3% range (10–12). In one study of patients with severe visual loss (,20/200 acuity), 32% of patients were found to harbor the NMO antibody, and in another study, the antibody was detected in 20% of patients with recurrent optic neuritis (13, 14). From the point of view of visual functions, the diagnosis of NMO is strongly suggested when the visual loss from optic neuritis is severe, bilateral, or recurrent or the recovery is poor. The difference in prognosis and treatment response of patients with NMO has lead some to conclude that it is worth getting an NMO titer on every patient with optic neuritis. Although the yield (about 5%) may be low (15), it is becoming harder to argue against routine testing for NMO if the result can have such important prognostic and therapeutic implications including the potential to worsen with interferon therapy (16). As Morrow and Wingerchuk (5) emphasize, relapse rates are higher in NMO compared with MS and disability milestones are achieved at a more rapid pace. At the very least, knowledge of the antibody status could prompt aggressive treatment if a subsequent attack ensues. The distinction of these 2 entities is critical because of the relatively poor visual prognosis of NMO and the differential response of these conditions to immunomodulatory therapy. It has become increasingly evident that interferon beta products may have a deleterious effect on the relapse rate of NMO, suggesting that the immunologic differences of these disorders have therapeutic implications (17, 18). For disease prevention, the present consensus is that patients with NMO should be treated with immunosuppressive agents such as azathioprine and mycophenolate mofetil or the anti-CD20