What ophthalmologists need to know about neuromyelitis optica spectrum disorder

(Image Credit: AdobeStock/Naeblys)

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, antibody (Ab)-mediated, inflammatory autoimmune disorder of the central nervous system (CNS). Historically, the core clinical features were myelitis and optic neuritis (ON), but a better understanding of the neuroimmunology and the target (aquaporin-4 [AQP4] water channel) in NMOSD have led to expanded diagnostic criteria for NMO as a spectrum disorder. Unlike relapsing and remitting multiple sclerosis (MS), attacks of NMOSD are more severe and sometimes irreversible, leading to acute neuronal loss, blindness, and paralysis.

Early diagnosis and treatment of NMOSD are crucial to prevent disability and improve survival rates, as untreated or undertreated NMOSD has a poor prognosis. Up to one-third of individuals die from the disease within 5 years after their initial attack. Left untreated, about half of patients with NMOSD will experience significant disability, including being confined to a wheelchair and vision loss.¹

Ophthalmologists may be the first point of contact for patients with NMOSD, and therefore, clinicians must be aware of the core criteria, recognize the disorder, order the serologic biomarker (AQP4), and refer for acute treatment. The pathogenic, serologic NMO-associated IgG Ab, which targets AQP4, is highly specific and differentiates NMOSD from MS.² AQP4, is a water channel protein found in the CNS, specifically on the foot processes of astrocytes at the blood-brain barrier. The term NMOSD arose in 2007 due to the wide range of symptoms characterized by damage to the high-density regions of AQP4 channel proteins, including the hypothalamus, optic chiasm, area postrema, and periependymal regions (Table 1).

When AQP4 Abs bind to astrocyte AQP4 channels, the complement cascade is activated and leads to the recruitment of granulocytes, eosinophils, and lymphocytes.³ This immune cell influx first damages the astrocytes and then the oligodendrocytes, resulting in demyelination of the CNS and neuronal loss.³ Although AQP4 is also found in other body areas such as the kidney, parietal cells of the stomach, airways, and secretory glands, these regions are equipped with complement inhibitors that may mitigate Ab-mediated damage.⁴

As NMOSD can be suspected through clinical examination, MRI is used to help differentiate NMOSD from other CNS inflammatory demyelinating disorders such as MS and myelin oligodendrocyte glycoprotein (MOG) Ab disease.⁵ In patients with NMOSD, MRI typically reveals lesions in AQP4-rich areas such as the hypothalamus, optic chiasm, area postrema, and brainstem (Table 2). NMOSD will also present with longitudinally extensive enhancement of the optic nerve or in the optic chiasm, leading to bilateral visual loss.⁵ In MOG Ab disease, the optic nerve sheath is typically involved, showing a tram-track appearance axially or a bull’s-eye appearance on coronal imaging, which differs from NMOSD. In MS, MRI typically shows periventricular, ovoid, multifocal white matter lesions in various stages of progression.

These lesions can also appear in the corpus callosum, indicating Dawson finger projection pattern.⁶ Typically, any demyelinating disorders that do not present with typical white matter lesions of MS should be tested for both MOG Ab disease and NMOSD. Despite similarities in presentation of various demyelinating disorders, patients with NMOSD can experience relapse rapidly with fatal outcomes, necessitating prompt recognition.

Race may also affect the incidence and progression of NMOSD, as findings from a previous study showed that Black patients in the US had an increased number of lesions on brain MRI compared with White patients.7 Younger White patients were found to present with ON and greater visual disability, whereas older patients of both races appeared to present with myelitis and greater motor disability.8 NMOSD appears to predominate in women compared with men, with a ratio of up to 10:1 in findings from some studies.¹⁰

When NMOSD is suspected, inpatient hospital admission is necessary to promptly initiate a course of high-dose steroids (HDSs), such as intravenous methylprednisolone, for 5 days. Oral prednisolone is then continued for a longer duration to maintain the effect. If symptoms do not remit/improve within 5 days of HDSs, then plasma exchange should begin.4 For NMOSD as well as MOG, is it important to note that the tapering of HDSs, typically 11 to 14 days, should be prolonged until the immunosuppression is controlled.

When AQP4 Abs remain positive following HDS/plasma exchange, long-term treatment is initiated. Immunosuppressive therapy is the mainstay for long-term treatment of NMOSD. Commonly used medications include azathioprine (AZA), mycophenolate mofetil (MMF), and rituximab. Findings from previous studies suggest that MMF may be superior to AZA in the treatment of NMOSD; however, AZA is preferred for younger female patients due to the teratogenic effects of MMF.⁴

In summary, NMOSD is a rare autoimmune disease affecting the CNS characterized by rapid degeneration, paralysis, and blindness. Ophthalmologists should be aware of the core clinical criteria, the radiographic findings, the need for early serologic testing for AQP4 antibodies, and the urgency of acute treatment as well as maintenance immunosuppression.

Early diagnosis and treatment are crucial to prevent disability and improve survival rates. Patients with ON (especially non-White patients or patients with bilateral ON) should be questioned about unusual symptoms, including area postrema syndrome (eg, unexplained hiccups, nausea, or vomiting). High-dose intravenous steroid therapy should be initiated when NMOSD is suspected, followed by plasma exchange if symptoms do not resolve within the first 3 to 5 days. Newer FDA-approved agents have shown safety and efficacy in reducing relapse and disability in seropositive NMOSD.

Jennifer Dunnigan, BS, from the McGovern School of Medicine at The University of Texas in Houston; Sneha Gajarla, BS, from the John Sealy School of Medicine at The University of Texas Medical Branch at Galveston; Osama Al Deyabat, MD, from the Department of Ophthalmology at Blanton Eye Institute at Houston Methodist Hospital; and Saif Alryalat, MD, all contributed to this article.

Andrew G. Lee, MD

E: aglee@houstonmethodist.org

Lee is affiliated with the Blanton Eye Institute at Houston Methodist Hospital in Texas. He has no financial disclosures related to this content.

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