Monitoring neuromyelitis optica activity

Abstract

Neuromyelitis optica (NMO) is a demyelinating and inflammatory disease essentially restricted to the spinal cord and the optic nerves. Emerging evidence indicates that serum antiaquaporin-4 (AQP4) antibodies have a critical role in its pathogenesis. NMO courses with multiple relapses, often leading to severe disability. Management of NMO focuses on the effective treatment of acute attacks and the prevention of relapses. The latter is currently attempted with immunosuppressive drugs. Although several factors have been associated with disease activity, especially serum levels of anti-AQP4 IgG, no single one of them has been proved clinically useful for guiding treatment. New drugs that target specifically AQP4 antibodies and complement activation are being developed; they may prove to be more efficient with fewer side effects.

Keywords::

• anti-aquaporin antibodies
• disease activity
• monitoring
• neuromyelitis optica
• optical coherence tomography
• treatment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Neuromyelitis optica (NMO) is a severely disabling syndrome, characterized by the development of optical neuritis and myelitis. Emerging evidence indicates that serum anti-AQP4 antibodies have a critical role in its pathogenesis.

• • Optical neuritis in NMO is characterized by frequent recurrences and a poor visual prognosis. Only one episode leads to legal blindness in almost one-third of patients.

• • Optical coherence tomography can provide useful information in NMO. Neurologists are becoming increasingly acquainted with this technique. The severity of axonal loss (greater in NMO), the presence of mycrocystic macular edema (more frequent in NMO) and the presence of subclinical damage in multiple sclerosis and not in NMO may help differentiate NMO from multiple sclerosis.

• • There are no randomized controlled trials in NMO. Therefore, treatment guidelines are based on retrospective studies and consensus opinion.

• • Acute attacks should be treated promptly and aggressively with high-dose intravenous methylprednisolone (1 g daily for 3–5 consecutive days). Plasma exchange should be considered early if there is little or no response.

• • Due to the severity of NMO episodes and the high risk for disability, immunosuppressive treatment should be implemented as soon as diagnosis is confirmed.

• • Emerging treatments try to target the cause of NMO, such as aquaporumab, a high-affinity monoclonal antibody that binds to anti-AQP4 antibodies or eculizumab, a humanized monoclonal antibody that inhibits a specific complement protein.

• • Relapses in NMO are frequently accompanied by an increase and immunosuppressive therapy by a decrease in serum anti-AQP4 IgG concentrations. As better assay methods for anti-AQP4 IgG are developed, the levels of this antibody may be used to monitor disease activity.

• • NMO may appear in children. It seems to have a better prognosis in terms of disability than adults. Pediatric NMO is characterized by frequent brain involvement at presentation. NMO-IgG antibody seropositivity is lower than in adults. Children with definitive NMO may be positive for AQP4-IgG, for myelin oligodendrocyte glycoprotein or for any of them.