. 2020 Dec 15;35(3):753–768. doi: 10.1038/s41433-020-01334-8

Table 2.

Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder.

Core clinical characteristics	AQP4-IgG positive	AQP4-IgG negative or unknown AQP4-IgG status	Additional MRI requirements in AQP4-IgG negative or unknown AQP4-IgG status
1. Optic neuritis 2. Acute myelitis 3. Area postrema syndrome: episode of otherwise-unexplained hiccups or nausea and vomiting 4. Acute brainstem syndrome 5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions 6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions	1. At least 1 core clinical characteristic 2. Exclusion of alternative diagnoses	1. At least 2 core clinical characteristics occurring as a result of 1 or more clinical attacks and meeting all of the following requirements: a. At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome b. Dissemination in space (2 or more different core clinical characteristics) c. Fulfilment of additional MRI requirements, as applicable 2. Negative tests for AQP4-IgG 3. Exclusion of alternative diagnoses	1. Acute optic neuritis: a brain MRI showing normal findings (or only non-specific white matter lesions), or an optic nerve MRI with a T2-hyperintense lesion or a T1-weighted gadolinium-enhanced lesion extending over more than one-half the optic nerve length or involving the optic chiasm 2. Acute myelitis: an associated intramedullary MRI lesion extending over either ≥3 contiguous segments (LETM) or ≥3 contiguous segments of focal spinal cord atrophy in patients with a history compatible with acute myelitis 3. Area postrema syndrome: associated dorsal medulla/area postrema lesions 4. Acute brainstem syndrome: associated peri-ependymal brainstem lesions

Core clinical characteristics

AQP4-IgG positive

AQP4-IgG negative or unknown AQP4-IgG status

Additional MRI requirements in AQP4-IgG negative or unknown AQP4-IgG status

1. Optic neuritis

2. Acute myelitis

3. Area postrema syndrome: episode of otherwise-unexplained hiccups or nausea and vomiting

4. Acute brainstem syndrome

5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions

6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions

1. At least 1 core clinical characteristic

2. Exclusion of alternative diagnoses

1. At least 2 core clinical characteristics occurring as a result of 1 or more clinical attacks and meeting all of the following requirements:

a. At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome

b. Dissemination in space (2 or more different core clinical characteristics)

c. Fulfilment of additional MRI requirements, as applicable

2. Negative tests for AQP4-IgG

3. Exclusion of alternative diagnoses

1. Acute optic neuritis: a brain MRI showing normal findings (or only non-specific white matter lesions), or an optic nerve MRI with a T2-hyperintense lesion or a T1-weighted gadolinium-enhanced lesion extending over more than one-half the optic nerve length or involving the optic chiasm

2. Acute myelitis: an associated intramedullary MRI lesion extending over either ≥3 contiguous segments (LETM) or ≥3 contiguous segments of focal spinal cord atrophy in patients with a history compatible with acute myelitis

3. Area postrema syndrome: associated dorsal medulla/area postrema lesions

4. Acute brainstem syndrome: associated peri-ependymal brainstem lesions

Adapted from Wingerchuk et al. [4].

AQP4 aquaporin-4, IgG immunoglobulin G, LETM longitudinally extensive transverse myelitis lesions, MRI magnetic resonance imaging, NMOSD neuromyelitis optica spectrum disorder.