There are predominantly 2 patterns of NMOSD: monophasic and relapsing. Monophasic NMOSD is diagnosed in approximately 10% of patients and occurs when 1 or both optic nerves and spinal cord are affected by a series of attacks over a short period of time (days or weeks), but after the initial attack, there is no recurrence.2,3 The relapsing form of NMOSD is diagnosed in approximately 90% of patients and is characterized by repeated attacks separated by periods of remission (weeks, months, or years).2,4

Specific laboratory tests for diagnosing NMOSD include blood tests for AQP4-IgG and MOG-IgG.2,7 The 2015 diagnostic criteria included APQ4-IgG positive tests but acknowledged that AQP4-IgG seronegativity has been found (in 10% to 25% of NMOSD cases), which suggests that there are other factors to be considered for NMOSD diagnosis.3,4 For example, antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs/anti-MOG antibodies) have been found in patients who are seronegative for AQP4-IgG.4,13,21

Thus, the IPND developed criteria for diagnosing 2 subtypes of NMOSD, with AQP4-IgG and without AQP4-IgG.3 Currently, 60% to 90% of NMOSD cases test positive for the AQP4-IgG antibody.9 Moreover, the antibody is found to be more prevalent in women and in patients with the relapsing form of the disease.7

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Diagnostic Workup

The most common diagnostic test used for diagnosing NMOSD is MRI of the brain, orbits, and spinal cord. Imaging of the CNS is typically performed with gadolinium, and follow-up examinations are obligatory.3 MRIs are conducted regularly to assess the progression of the disease based on new or active lesions and to correlate specific symptoms to lesion locations. Abnormal enhancement indicates active inflammation.4,15

Detection of LETM spinal cord lesions associated with optic neuritis is the most specific neuroimaging characteristic of NMOSD.3 Transverse myelitis typically refers to inflammation of 1 segment of the spinal cord, which can be from a variety of causes. LETM occurs when there is more extensive spinal cord involvement, and spans 3 or more vertebral segments. LETM is not specific to NMOSD; other conditions can cause LETM. Figure 1 shows an MRI image of LETM.22

Figure 1. Longitudinally extensive transverse myelitis on MRI of the cervical spine.22(Top) Hyperintense signal extending over 3 spinal cord segments on sagittal T2-weighted MRI; (bottom) Hyperintense signal in the central/dorsal cord on axial T2-weighted MRI. Reprinted from Oh et al.22

Brain or orbit MRI can show enhancement of the optic nerves, but brain imaging is otherwise typically normal in early NMOSD. The use of orbit MRI is preferred to detect optic neuritis with greater accuracy than brain MRI.3 Brain lesions may later develop and are typically located close to the ventricles near the diencephalon and hypothalamus where there is high AQP4 expression.7 In the case of APS associated with NMOSD, brain lesions may appear in the medulla oblongata. Figures 2 and 3 show examples of such lesions.16,23

Figure 2. Medullary lesion of APS.16 A) Medullary lesion on axial MRI fluid-attenuated inversion recovery image; B) Medullary lesion on sagittal T2-weighted MRI image. Reprinted from Apetse et al.16
Figure 3. Lesion in the left medulla area postrema on MRI fluid-attenuated inversion recovery image.23
Reprinted from Dandu et al.23

A lumbar puncture may be performed to examine the cerebrospinal fluid in NMOSD. Cerebrospinal fluid findings include elevated white blood cells and elevated protein. Oligoclonal bands are typically infrequent in NMOSD (<20%), and are found more frequently in patients with MS (>80%). An initial finding of oligoclonal band positivity, which is then followed by oligoclonal band negativity later in the disease course, may be indicative of NMOSD and not MS.7,24

Referral to an ophthalmologist should be ordered for a complete eye examination. Optical coherence tomography is performed by taking images of the retina. Unmyelinated CNS axons within the retina are identified as the retinal nerve fiber layer. Optical coherence tomography is used as a means of measuring disease progression by examining the damage, observed as thinning, of the retinal nerve fiber layer. This imaging technique can be used to diagnose many other eye disorders as well. A single acute attack of optic neuritis causes more severe damage to the retinal nerve fiber layer in NMOSD than in MS.7,24