International Consensus Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorders

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Wingerchuk DM, Banwell B, Bennett JL et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015.

The International Panel for NMO Diagnosis (IPND) recently released an updated set of guidelines for diagnosing Neuromyelitis Optica (NMO) and Neuromyelitis Optica spectrum disorders (NMOSD). NMO is an inflammatory disorder of the central nervous system. The guidelines for diagnosing NMO that were released in 2006 were recently revised based on research advances and an increased understanding of the disorder.

The IPND has eliminated the use of NMO, and is now referring to the disease as NMOSD. This is because individuals with NMO and NMOSD generally do not have differing clinical behavior and should receive the same treatment. The IPND also agreed not to have the diagnosis of NMOSD be solely based on the presence of AQP4-IgG.

Diagnostic criteria for NMOSD with AQP4-IgG, NMOSD without AQP4-IgG or with unknown AQP4-IgG status were established along with a set of core clinical characteristics to aid in diagnosing those with potential NMOSD. The diagnostic requirements are more stringent in those without AQP4-IgG, and require 2 core clinical characteristics, one of which has to be optic neuritis, acute myelitis with longitudinally extensive transverse myelitis (a lesion extending 3 or more vertebral segments), or lesions in the area of the brain that causes vomiting, as well as other MRI characteristics. Those who are AQP4-IgG positive require just one core clinical characteristic. The panel recommends cell-based serum assays to detect AQP4-IgG because they are the most accurate, but unfortunately they are not yet widely available.

A set of “red flags” were identified that do not exclude NMOSD if present, but may indicate another diagnosis:

  1. A very short (less than 4 hours) time to the worst part of an attack,
  2. or very long (more than 4 weeks) time to the worst part of an attack,
  3. and presence of oligoclonal bands in the cerebrospinal fluid.

Neuroimaging characteristics of NMO include:

  1. LETM
  2. a lesion in the central part of the cord,
  3. and certain NMOSD-typical brain lesion patterns.

According to the panel, the characteristics of pediatric NMOSD are similar to adult NMOSD, and the proposed criteria can generally be used in this population, although they note that a LETM lesion is not as specific for NMO in children as it is in adults because LETM can occur in 15% of children with MS, and can also occur in ADEM.

5-10% of NMOSD cases are monophasic, but it is unclear what criteria indicate that someone will maintain a monophasic disease course. The panel recommends that someone be considered to have monophasic NMOSD only after they have been relapse free for five or more years, but those who are AQP4-IgG positive should be considered to be at high risk for recurrence regardless of the length of time between attacks.

DIAGNOSTIC CRITERIA FOR NMOSD WITH AQP4-IGG

  1. At least 1 core clinical characteristic
  2. Positive test for AQP4-IgG using best available detection method (cell-based assay strongly recommended)
  3. Exclusion of alternative diagnoses

DIAGNOSTIC CRITERIA FOR NMOSD WITHOUT AQP4-IGG OR UNKNOWN AQP4-IGG STATUS

  1. At least 2 core clinical characteristic occurring as a result of one or more clinical attacks and meeting all of the following requirements:
    1. At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome
    2. Dissemination in space (2 or more core clinical characteristics)
    3. Fulfillment of additional MRI requirements, as applicable
  2. Negative test for AQP4-IgG using best available detection method, or testing unavailable
  3. Exclusion of alternative diagnoses

CORE CLINICAL CHARACTERISTICS

  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

ADDITIONAL MRI REQUIREMENTS FOR NMOSD WITHOUT AQP4-IGG OR UNKNOWN AQP4-IGG STATUS

  1. Acute optic neuritis: requires brain MRI showing (a) normal findings or only nonspecific white matter lesions, OR (b) optic nerve MRI with T2-hyperintense lesion or T1-weighted gadolinium-enhancing lesion extending over 1/2 optic nerve length or involving optic chiasm
  2. Acute myelitis: requires associated intramedullary MRI lesion extending over 3 or more contiguous segments (LETM) OR 3 or more contiguous segments of focal spinal cord atrophy in patients with history compatible with acute myelitis
  3. Area postrema syndrome: requires associated dorsal medulla/area postrema lesions
  4. Acute brainstem syndrome: requires associated periependymal brainstem lesions