Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease often characterized by sporadic and repeated inflammatory flare ups that can impact the optic nerve and/or spinal cord. With each repeated attack, additional permanent neurological damage will accrue.

Symptoms of these attacks vary but the most common symptoms are associated with inflammation of the optic nerve and spinal cord (e.g., optic neuritis and longitudinally extensive transverse myelitis) and may include pain inside the eye, loss of vision acuity, pain in the spine or limbs, paraparesis or paraplegia, and loss of bowel and bladder control.

One concern with this condition is that it may not be until a second or third attack that the disease is properly diagnosed and permanent damage has already occurred. A report by Mealy et al (2019) noted that the mean delay in diagnosis or use of a preventive treatment was 3.6 years (+ 5.0) in a cohort of 182 individuals with NMOSD.  This is unfortunate given that there are three treatments approved to manage individuals with NMOSD – eculizumab, satralizumab, and  inebilizumab – and all three treatments have been shown to reduce the risk of relapse.

Historically, a delay in diagnosis was attributed to the fact that the symptoms of NMOSD can be similar to those observed in multiple sclerosis (MS). Both MS and NMOSD are idiopathic, autoimmune, inflammatory disorders of the central nervous system that frequently affect the optic nerves.

Making a diagnosis of NMOSD is fairly straight forward once the disease is on the clinician’s index of suspicion. Most individuals with NMOSD express autoantibodies AQP-4 channel and that observation can help in diagnosing this rare condition.

Once a person is suspected of having NMOSD, testing for AQP4-IgG can often lead to a diagnosis (see table below for diagnostic criteria). And even in persons who are not positive for AQP4-IgG, there are patterns of symptoms to suspect NMOSD that can lead to a diagnosis.

Table. NMOSD Diagnostic Criteria in Adults [Wingerchuk 2015]
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

3. Exclusion of alternative diagnoses

Diagnostic criteria for NMOSD without AQP4-IgG or NMOSD with unknown AQP4-IgG status 1. At least 2 core clinical characteristics occurring as a result of one 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. Fulfillment of additional MRI requirements, as applicable

2. Negative tests 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 and NMOSD with 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 contiguous segments (LETM) OR  >3 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

 

For many people with NMOSD, one of the first specialists they may encounter with symptoms is an ophthalmologist.  Fortunately, numerous studies have been published recently that may help those specialists in suspecting NMOSD and distinguish it from other conditions, such as MS.

For example, optic neuritis in NMOSD is generally more severe and more likely to present with simultaneous bilateral or rapidly sequential eye involvement. [Patterson, 2017; Levy, 2020] Posterior involvement of the optic chiasm and optic tracts may also be present. Furthermore, NMOSD patients experiencing optic neuritis tend to show decreased color vision or “red desaturation” (red objects look orange or gray from the affected eye).

 

Research and Clinical Trials

For general clinical trial information, please visit ClinicalTrials.gov, the most comprehensive database of privately and publicly funded clinical studies conducted around the world. For specific clinical trial information on NMOSD, visit here.

For information about ongoing research in NMOSD, visit Guthy Jackson Charitable Foundation. This nonprofit organization funds research focused on  prevention, clinical treatments, and an eventual cure for this rare disease. A description of funded research projects is available.

 

Advocacy Groups

Guthy-Jackson Charitable Foundation is dedicated to funding basic science research to find answers that will lead to the prevention, clinical treatment programs and a potential cure for NMOSD. They are committed to providing an online community for those who have been diagnosed with this rare autoimmune disorder, as well as providing centralized information resources for individuals who want to learn more about this rare disease.

The Siegel Rare Neuroimmune Association (SRNA) is a not-for-profit international organization dedicated to the support of children, adolescents, and adults with a spectrum of rare neuroimmune disorders including: Acute Disseminated Encephalomyelitis (ADEM), Acute Flaccid Myelitis (AFM), MOG Antibody-Associated Disease (MOG-Ab disease), NMOSD, Optic Neuritis (ON) and Transverse Myelitis (TM). They support individuals living with rare neuroimmune diagnoses and their families, promote awareness to empower patients, families, clinicians and scientists, build a collaborative clinical care network and help advance scientific understanding and research.

 

Recommended Reading
  • Holroyd K, Manzano G, Levy M. Update on neuromyelitis optica spectrum disorder.  Current Opin Ophthalmol. 2020 Sep.
  • Huda S, Whittan D, Bhojak M, et al. Neuromyelitis optica spectrum disorders. Clin Med.2019; 19: 169-177.
  • Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015; 85:177-189.
  • Borisow N, Mori M, Kuwabara S, Scheel M, Paul F. Diagnosis and Treatment of NMO Spectrum Disorder and MOG-Encephalomyelitis. Front Neurol. 2018; 9: 888.
  • National Organization or Rare Disorders (NORD) Rare Disease Databases. Neuromyelitis Optica. Available at https://rarediseases.org/rare-diseases/neuromyelitis-optica/
  • Mealy MA, Mossburg SE, Kim S-H, et al. Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions. Mult Scler Relat Disord. 2019; 28: 64-68.
  • Patterson SL, Goglin SE. Neuromyelitis optica. Rheum Dis Clin N Am. 2017; 43: 579-591.
  • Sheh T, You Y, Arunachalam S, et al. differing structural and functional patterns of optic nerve damage in multiple sclerosis and neuromyelitis optica spectrum disorder. 2019;126:445-453.
  • Manogaran P, Hanson JVM, Olbert ED, et al. Optical coherence tomography and magnetic resonance imaging in multiple sclerosis and neuromyelitis spectrum disorder. Int J Mol Sci. 2016; 17: 1894.
  • Zhang X, Xiao H, Liu C, et al. Comparison of macular structural and vascular changes in neuromyelitis optica spectrum disorder and primary open angle glaucoma: a cross- sectional study. Br J Ophthalmol. 2020; Epub ahead of print.  doi:10.1136/ bjophthalmol-2020-315842