Neuromyelitis Optica Spectrum Disorder Diagnosis and Characteristics

Clinical Presentations

The American College of Radiology suggests that severe optic neuritis, often bilateral and simultaneous, with posterior optic nerve involvement extending to the chiasm, and long optic nerve lesions on MRI, is a hallmark clinical syndrome that should immediately raise suspicion for NMOSD 1, 2
The International Panel on Multiple Sclerosis recommends that longitudinally extensive transverse myelitis (LETM), spinal cord inflammation spanning ≥3 contiguous vertebral segments, is a key clinical feature of NMOSD 1, 3, 4

The International Panel on Multiple Sclerosis recommends that definite NMOSD requires optic neuritis AND acute myelitis AND at least 2 of the following 3 supportive criteria, including contiguous spinal cord MRI lesion extending ≥3 vertebral segments, brain MRI at onset nondiagnostic for MS, or NMO-IgG (aquaporin-4 antibody) seropositivity 1
For AQP4-IgG positive patients, revised criteria allow diagnosis with at least one core clinical characteristic, such as optic neuritis, myelitis, area postrema syndrome, brainstem syndrome, diencephalic syndrome, or cerebral syndrome 4

The Journal of the American College of Radiology suggests that MRI features that distinguish NMOSD include spinal cord lesions that are longitudinally extensive (≥3 segments), often with central cord involvement and associated swelling 3, 4
The Lancet Neurology recommends that optic nerves show T2 hyperintensity with gadolinium enhancement extending over half the optic nerve length or involving the optic chiasm 2, 4

The Journal of Neuroinflammation warns that delaying diagnosis waiting for dissemination in space can be harmful, as many MOG-EM and NMOSD patients present with isolated syndromes that warrant immediate testing 5
The American College of Radiology advises that assuming all NMOSD is AQP4-positive can be incorrect, as approximately 25% are seronegative, and some may have anti-MOG antibodies requiring different management considerations 1

Area postrema syndrome is characterized by intractable nausea, vomiting, and hiccups, according to the Journal of Neuroinflammation 6, 7
Brainstem syndromes with peri-ependymal brainstem lesions are a clinical feature of NMOSD, as reported in The Lancet Neurology 8
Diencephalic and cerebral syndromes affecting regions around the third and fourth ventricles are also associated with NMOSD, as described in the Journal of the American College of Radiology 9

Brain MRI at onset that is nondiagnostic for MS is a supportive criterion for NMOSD diagnosis, according to The Lancet Neurology 8

Longitudinally extensive lesions affecting ≥3 vertebral segments (LETM) are characteristic of NMOSD, often with central cord involvement and associated swelling, as described in Brain 10, 11
Lesions are typically T1 hypointense and show prominent cord swelling, with a "cloud-like" enhancement pattern that is poorly marginated, distinct from MS, as reported in Brain 11
Long optic nerve lesions with T2 hyperintensity and gadolinium enhancement extending over half the optic nerve length or involving the optic chiasm are also characteristic of NMOSD, as described in Brain 10

MS lesions are typically small (<2 vertebral segments), peripheral, and wedge-shaped, whereas NMOSD shows LETM, as reported in Brain 11
MS brain lesions show periventricular ovoid lesions and Dawson's fingers, which are absent in typical NMOSD, according to the Journal of Neuroinflammation 6, 7
CSF oligoclonal bands are typically absent in NMOSD but present in 85-95% of MS cases, as described in the Journal of Neuroinflammation 6, 7

Some seronegative patients may have anti-MOG antibodies, representing a distinct entity (MOG-antibody disease) requiring different management, according to the Journal of Neuroinflammation 6