Diagnosis

The diagnosis of NMO, rather than MS, in a patient with a history of ON (Fig. 47-1) and myelitis is largely dependent on documentation of longitudinally extensive spinal cord lesions (more than three spinal segments). Such extensive intramedullary spinal cord lesions are unique to NMO in contrast to the very short segment MRI findings in MS (Fig. 47-2).

Figure 47-1 Optic Nerve Atrophy.

Figure 47-2 Neuromyelitis Optica.

A very specific NMO-IgG serum autoantibody is identified that binds to the central nervous system (CNS)–dominant water channel aquaporin-4, a structure that is normally present on astrocytes. This leads to the primary pathologic change, namely, loss of this aquaporin-4 water channel protein. This is occasionally associated with secondary demyelination. Hypothalamic and periventricular demyelination, the latter previously thought to be almost MS specific, are now also recognized to be associated with NMO-IgG/anti-AQP4 seropositivity. This particular distribution of lesions corresponds with the site of AQP4 expression within the brain. Preliminary experiments suggest that anti-AQP4 autoantibodies are pathogenic. This antibody has a high sensitivity and specificity for NMO being present in at least 75% of these cases; its presence now provides a specific diagnostic modality. This totally contrasts with MS, where there is nothing absolutely specific present to confirm that diagnosis.

Prognosis

When one is confronted with a new case of ON, the testing for NMO-related anti-AQP4 antibodies is very important diagnostically as well as prognostically. In this setting, the finding of this specific seropositivity predicts poor future visual outcome, and possibly rapid onset of NMO. In the converse, the patient presenting with longitudinally extensive transverse myelitis (LETM) and who is found to be antibody positive for the NMO antibody has more than a 50% chance of developing ON or recurrent severe ON within just 1 year. This is an important designation as NMO has a much worse prognosis than MS per se because the antibody-positive NMO patient does not respond to the usual immunomodulatory treatments that are often initially effective for MS.

Treatment