Early Treatment Improves Outcomes in Neuromyelitis Optica Spectrum Disorder

The 2015 Diagnostic Criteria

Deepening understanding of NMOSD led to the development of new diagnostic criteria in 2015. The criteria identify optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic syndrome with MRI lesions typical of NMOSD, and symptomatic cerebral syndrome with MRI lesions typical of NMOSD as the six core clinical characteristics. If the patient tests positive for AQP4 antibodies and has one core clinical characteristic, a diagnosis of NMOSD is appropriate. If the patient tests negative for AQP4 antibodies, he or she must have two or more core clinical characteristics (at least one of which should be optic neuritis, acute myelitis, or area postrema syndrome) that are disseminated in space for a diagnosis of NMOSD to be appropriate. In both cases, alternative diagnoses also must be excluded.

Some patients who test negative for AQP4 antibodies have myelin oligodendrocyte glycoprotein (MOG) antibodies. Although AQP4-mediated NMOSD and MOG-mediated NMOSD are clinically similar, they are distinct diseases, said Dr. Pawate. Pathology primarily affects myelin, not astrocytes, in MOG-positive NMOSD. Patients with MOG-positive NMOSD also tend not to have relapses, and the disorder has a better prognosis, compared with AQP4-positive NMOSD.

Between 15% and 30% of patients with NMOSD have oligoclonal bands, and 20% have an elevated IgG index. Unlike in MS, however, these findings tend to be transient. In addition, as much as 30% of patients with NMOSD may have other comorbid autoimmune disorders. A review of the literature indicated that 22 autoimmune conditions, including myasthenia gravis, ulcerative colitis, hypothyroidism, and thrombocytopenia, have been observed in patients with NMOSD. “We think that this indicates a heightened autoimmune response in general in those patients,” said Dr. Pawate.

Treatment of NMOSD

Treatment of NMOSD is based on the principle that relapses, which can be severe, result in disability. The disease does not progress between relapses, unlike MS. Therefore, the consensus is that relapses should be treated promptly and aggressively. Maintenance immunosuppression may prevent future relapses, and other symptoms can be managed as needed. “I have had a patient for 10 years now who, after the first attack, has not had any more attacks and is living fairly normally,” said Dr. Pawate.

Evidence supports plasma exchange as a standard treatment for relapses in NMOSD. It requires five to seven sessions and 1.5 volumes. This treatment removes antibodies and other soluble disease mediators, such as complement. Bonnan and Cabre found that administering plasma exchange early in the relapse can mitigate astrocyte dysfunction and prevent neuronal death.

In a 2012 study, patients with optic neuritis were treated with IV corticosteroids or IV corticosteroids plus plasma exchange. Approximately 75% of patients treated with plasma exchange had a final visual acuity better than 20/40, compared with 39% of patients who received steroids alone. About 13% of patients treated with plasma exchange had a final visual acuity worse than 20/200, compared with 56% of patients who received steroids alone.

In 2017, Bonnan et al found that short delay to plasma exchange is the strongest predictor of outcome in severe attacks of NMOSD. The rate of good recovery was approximately 80% when plasma exchange was performed within a day or so of relapse onset. Plasma exchange also was effective when administered at a week after onset. The therapeutic window closes at approximately three weeks after onset, said Dr. Pawate.

Neurologists should begin maintenance immunosuppression immediately, said Dr. Pawate. Rituximab has the best evidential support for this indication, but the drug can be expensive, and insurance reimbursement is not easy to obtain. Only one formal publication has examined mycophenolate, but neurologists have a lot of clinical experience with this treatment. It takes three to four months before mycophenolate achieves its full efficacy, so bridge therapy is required. Mealy et al found that with optimal dosing, rituximab reduces patients’ relapse rate by 94%, mycophenolate reduces it by 90%, and azathioprine reduces it by 72%.

In one case series, tocilizumab, a monoclonal antibody targeting IL-6, was effective in patients who had not responded to rituxi­mab. Eculizumab, a mono­clonal antibody targeting the complement factor C5a, may be another option, based on recent reports. Maintenance immunosuppression should continue for at least five years, and indefinitely for patients with AQP4 antibodies, said Dr. Pawate.

If it is not clear whether the diagnosis is NMOSD or MS, a neurologist should treat the patient for NMOSD, said Dr. Pawate. Mycophenolate and rituximab, the two most commonly used NMOSD treatments, are effective against MS as well, but several treatments for MS, such as natalizumab, fingolimod, and interferon beta, may exacerbate NMOSD.

A clinical evaluation is the best way to monitor the treatment’s effect, said Dr. Pawate. “Make sure they are not having any new symptoms, new vision complaints, new motor weakness, or sensory complaints. MRI is of limited value in treatment monitoring…. Basically, nothing substitutes for talking to the patient and performing an examination.”