Neuromyelitis Optica Spectrum Disorder Presents Diagnostic and Treatment Challenges

“AQP4 antibody disease is a relapsing condition when untreated,” said Dr. Palace. “On the other hand, many MOG antibody seropositive patients have monophasic phenotypes.” Other monophasic conditions include LETM or idiopathic transverse myelitis, Devic’s disease, and severe or bilateral optic neuritis.

Patients in the monophasic group may go on to develop relapsing disease (ie, relapsing NMOSD, relapsing optic neuritis, and relapsing LETM), Dr. Palace noted. Among the difficult-to-treat patients are those who have overlap between MS and antibody-negative NMOSD.

Management of an acute attack across all of these monophasic syndromes is similar because the attacks tend to present with more severe relapses than patients with MS, and some patients are left with severe residual disability, said Dr. Palace. “We treat these patients urgently with IV methylprednisolone for three to five days to try to restore function. If there is poor response or significant disability, we follow with plasma exchange.” If plasma exchange is not feasible, patients may be given IV immunoglobulin (IVIG), she suggested. “There is a small proportion of patients who develop severe paraplegia that don’t appear to respond at all to treatment, even if given urgently. In my experience, these patients are monophasic and they are antibody negative for both MOG and AQP4.”

Patients with acute disseminated encephalomyelitis can rebound if given a short course of IV methylprednisolone. Dr. Palace recommended follow-on prednisolone for two months for patients who have such monophasic MOG and AQP4 antibody disorders to prevent rebound, and for longer (ie, six to 12 months) for monophasic patients with MOG antibodies.

Preventing relapse is probably the most important aspect of managing NMOSD. “AQP4 antibody disease is a relapsing condition, and there is no progressive phase as there is in MS,” Dr. Palace said. “There is a high morbidity and mortality associated with relapse.”

In a 2012 review of AQP4 antibody-seropositive patients—many of whom were on corticosteroids or other immunosuppression—researchers found that, among 59 patients in the UK with a median follow-up of five years, 22% had permanent bilateral visual loss with visual acuity of less than 6/36 in the better eye, and nearly 30% were wheelchair-dependent.

Prednisolone cover alone or in conjunction with a steroid-sparing drug (ie, azathioprine, mycophenolate, methotrexate, or rituximab) is the recommended first-line treatment for relapse prevention. “If patients have a relapse on an adequate dose tried for three to six months, then you might consider an alternative first-line drug or other less commonly used immunosuppressive agents such as ciclosporin/tacrolimus, cyclophosphamide, or mitoxantrone. Regular plasma exchange or IVIG is also an option,” said Dr. Palace. “We note that our patients appear less likely to relapse if they are kept on a low background dose of prednisolone when on other immunosuppressants. If they have a relapse, we may increase the background prednisolone dose rather than switch treatments.”

Some MS disease-modifying drugs have been reported to exacerbate NMOSD, including beta-interferon, natalizumab, and fingolimod. In addition, there is a theoretical risk of alemtuzumab being harmful because it is known to precipitate antibody-mediated disease, Dr. Palace said.

—Adriene Marshall