Neuromyelitis Optica Spectrum Disorder (NMOSD)


New diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) were listed in the issue of the journal Neurology published on July 14, 2015. This publication followed a thorough review of the existing medical literature by an international consensus panel, led by Dean Wingerchuk, MD, from the Mayo Clinic in Rochester, Minnesota.1

Core Clinical Characteristics 

The consensus panel identified 6 core clinical characteristics of NMOSD, including the following2:

  1. Optic neuritis
  2. Acute myelitis
  3. Area postrema syndrome: an episode of otherwise unexplained hiccups or emesis and nausea
  4. Acute brainstem syndrome
  5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic lesions on magnetic resonance imaging (MRI)
  6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions 

Diagnostic Criteria for NMOSD With and Without AQP4-IgG Autoantibodies

The panel determined the following diagnostic criteria for NMOSD with aquaporin-4 immunoglobulin G (AQP4-IgG)2 autoantibodies:

  1. Minimum of 1 core clinical characteristic
  2. Positive result of test for AQP4-IgG with use of cell-based assays for best detection
  3. Exclusion of other diagnoses 

The panel determined the following diagnostic criteria for NMOSD without AQP4-IgG autoantibodies or unknown AQP4-IgG status2:

  1. Minimum of 2 core clinical characteristics during 1 or more clinical episodes that meet the following requirements:
    1. At least 1 core clinical characteristic consisting of optic neuritis, acute myelitis with longitudinally extensive transverse myelitis (LETM) lesions, or area postrema syndrome
    2. Dissemination in space (2 or more different core clinical characteristics)
    3. Fulfillment of additional MRI requirements, including the following:
      1. Acute optic neuritis: brain MRI showing either normal or nonspecific white matter lesions OR optic nerve MRI showing optic nerve lesion covering more than half the nerve length or involving the optic chiasm
      2. Acute myelitis: intramedullary MRI lesion extending for 3 or more contiguous segments (longitudinally extensive transverse myelitis [LETM]) OR 3 or more contiguous segments of focal spinal cord atrophy compatible with acute myelitis
      3. Area postrema syndrome: MRI showing dorsal medulla/area postrema lesions
      4. Acute brainstem syndrome: MRI showing peri-ependymal brainstem lesions
  2. Negative test for AQP4-IgG autoantibodies with use of best detection available or testing unavailable for unknown status
  3. Exclusion of other diagnoses 

Diagnostic Process

To obtain a diagnosis of NMOSD, a neurologist examines the patient to assess movement, muscle strength, coordination, sensation, cognition, vision, and speech. A complete medical history describing all symptoms is documented.3,4 

An ophthalmologist may complete a separate eye examination, including optical coherence tomography (OCT).3,4

MRI is performed to assess the optic nerves, spinal cord, and brain for the presence of neural lesions in specific regions.3 MRI may differentiate NMOSD from multiple sclerosis (MS). MS lesions tend to be more widespread, peripheral, and patchy throughout the central nervous system (CNS), whereas NMO lesions are typically more centrally located, localized to the optic nerves and spinal cord.5 

Blood tests, in particular cell-based assays, evaluate for the presence of the autoantibody NMO-IgG to differentiate NMOSD from MS and other neurological diagnoses. A myelin oligodendrocyte glycoprotein (MOG-IgG) antibody test may also be performed to rule out another inflammatory disorder (MOG-IgG–associated optic neuritis, encephalitis, and myelitis) with symptoms similar to those of NMOSD.3,4 

A lumbar puncture may assess the cerebrospinal fluid for elevated levels of inflammatory biomarkers—specifically antibodies, immune cells (white blood cells), and proteins in the fluid surrounding the CNS. This may also help differentiate NMOSD from MS because white blood cell counts tend to be higher during acute flare-ups of NMOSD than they are in MS.3,4 

A stimulus response test evaluates the time it takes the brain to react to stimuli including sights, sounds, and touches. These evoked response tests may help localize damage within the nerves, spinal cord, brain or brainstem, and optic nerves.3 

It is important to diagnose NMOSD early because without proper treatment acute flare-ups may cause irreversible nerve damage.4

Types of NMOSD

An accurate diagnosis should determine which of the 2 types of NMOSD is present in an affected individual. Of the 2 types, the relapsing form is more common, manifesting more frequently in women than in men. Relapses characteristically consist of periodic flare-ups with recovery between episodes. The monophasic form manifests equally often in men and women, occurring as a single attack lasting around 1 or 2 months.6 

References

  1. Hughes S. New name, diagnostic criteria for neuromyelitis optica. Medscape. Published July 17, 2015. Accessed October 13, 2021. 
  2. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/WNL.0000000000001729
  3. Neuromyelitis optica – diagnosis and treatment. Mayo Clinic. Accessed October 13, 2021.
  4. Symptoms and diagnosis of NMO. National Multiple Sclerosis Society. Accessed October 13, 2021. 
  5. Lalan S, Khan M, Schlakman B, Penman A, Gatlin J, Herndon R. Differentiation of neuromyelitis optica from multiple sclerosis on spinal magnetic resonance imaging. Int J MS Care. 2012;14(4):209-214. doi:10.7224/1537-2073-14.4.209
  6. Neuromyelitis optica. Johns Hopkins Medicine. Accessed October 13, 2021.

Reviewed by Harshi Dhingra, MD, on 10/10/2021.

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