Neuromyelitis Optica Spectrum Disorder (NMOSD)


Neuromyelitis optica spectrum disorders (NMOSDs) are a group of autoimmune disorders of varying severity that are caused by degeneration of the myelin surrounding the optic nerves and spinal cord. In most cases, immunoglobulin G (IgG) autoantibodies attack aquaporin-4 (AQP4) water channels, which are located predominantly in the spinal cord and optic nerves.1

In a study published in 2021, the authors reported that 35 of 67 patients (52.2%) with NMOSD had at least one comorbidity. They determined that of 44 NMOSD-associated comorbidities, 29 were somatic, 13 were psychiatric, and 2 were autoimmune. They also noted that 24 of the comorbidities had appeared before NMOSD was diagnosed.2

Somatic Comorbidities

The most common somatic comorbidities in the 2021 study included migraine (8.9%), iron deficiency anemia (14.8%), and non-autoimmune hypothyroidism (6%).2 

Another study, in which individuals with NMOSD were compared with matched, non-NMOSD controls, observed statistically significant differences between the 2 groups in rates of the following comorbidities: hypertension (30.9% vs 24.9%), cardiovascular disease (27.2% vs 10.1%), diabetes (16.1% vs 8.9%), hyperglycemia (7.4% vs 3.2%), and liver disease ​​(excluding infection; 6.8% vs 2.4%).3 

It has been suggested that NMOSDs and some of the associated comorbidities may result from similar predisposing genetic or environmental factors, or from corticosteroid treatment of NMOSD to suppress inflammation. Corticosteroids may lead to the development of diabetes and hyperglycemia, whereas other immunosuppressive medications are associated with the development of cardiovascular disease.3 

Psychiatric Comorbidities

In the 2021 study, the psychiatric comorbidities that most frequently accompanied NMOSD included anxiety disorders (10.4%) and major depressive disorder (8.9%). Researchers noted that the frequency of psychiatric disorders was statistically significantly higher in patients with AQP4-IgG positive NMOSD.2

Investigators in a 2016 study concluded that moderate to severe depression in individuals with NMOSD is related to chronic neuropathic pain and fatigue and is undertreated, with only approximately 40% of these patients receiving antidepressant medical intervention.4

Autoimmune Comorbidities

A systematic review of the literature demonstrated that Sjögren syndrome and systemic lupus erythematosus are the systemic autoimmune comorbidities that most frequently accompany NMOSD.5 Other autoimmune disorders associated with NMOSD include myasthenia gravis, autoimmune thyroid disease, rheumatoid arthritis, and autoimmune encephalitis.3,5 One study estimated that approximately 30% of patients with NMOSD have a concomitant autoimmune disease—most commonly systemic lupus erythematosus, Sjögren syndrome, or autoimmune hypothyroidism.3

The connection between NMOSD and comorbid autoimmune disease is unclear, although the authors of one study speculated that NMOSD either is just one manifestation of a genetic predisposition to autoimmunity or is the central nervous system manifestation of a multisystemic rheumatologic disease.6

Cognitive Impairments

Cognitive impairments are common in patients with NMOSD, including deficits in attention, information processing speed, executive function, language, concentration, and verbal memory.7,8 Although the specific domain of cognitive dysfunction varies from study to study, the forms of dysfunction most commonly seen in NMOSD are attention deficit and poor memory performance.9 

Saji et al postulated that a unique dynamic between astrocytes and AQP4-IgG autoantibodies results in significant, diffuse neuronal loss in cortical gray matter that may contribute to the observed cognitive deficits.8 AQP4 expression, which plays a key role in the regulation of synaptic neuroplasticity, may be affected by AQP4-IgG autoantibodies.10

References

  1. Neuromyelitis optica spectrum disorder. NORD (National Organization for Rare Disorders). Accessed October 26, 2021.
  2. Barzegar M, Mirmosayyeb O, Nehzat N, Vaheb S, Shaygannejad V, Asgari N. Frequency of comorbidities in neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2021;48:102685. doi:10.1016/j.msard.2020.102685
  3. Exuzides A, Sheinson D, Sidiropoulos P, et al. Burden and cost of comorbidities in patients with neuromyelitis optica spectrum disorder. J Neurol Sci. 2021;427:117530. doi:10.1016/j.jns.2021.117530
  4. Chavarro VS, Mealy MA, Simpson A, et al. Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3:e286. doi:10.1212/NXI.0000000000000286
  5. Shahmohammadi S, Doosti R, Shahmohammadi A, et al. Autoimmune diseases associated with neuromyelitis optica spectrum disorders: a literature review. Mult Scler Relat Disord. 2019;27:350-363. doi:10.1016/j.msard.2018.11.008
  6. Wingerchuk DM, Weinshenker BG. The emerging relationship between neuromyelitis optica and systemic rheumatologic autoimmune disease. Mult Scler J. 2012;18(1):5-10. doi:10.1177/1352458511431077
  7. Meng H, Xu J, Pan C, et al. Cognitive dysfunction in adult patients with neuromyelitis optica: a systematic review and meta-analysis. J Neurol. 2017;264:1549-1558. doi: 10.1007/s00415-016-8345-3
  8. Saji E, Arakawa M, Yanagawa K, et al. Cognitive impairment and cortical degeneration in neuromyelitis optica. Ann Neurol. 2013;73:65-76. doi: 10.1002/ana.23721
  9. Oertel FC, Schließeit J, Brandt AU, Paul F. Cognitive impairment in neuromyelitis optica spectrum disorders: a review of clinical and neuroradiological features. Front Neurol. 2019;10:608. doi:10.3389/fneur.2019.00608
  10. Hubbard JA, Szu JI, Binder DK. The role of aquaporin-4 in synaptic plasticity, memory and disease. Brain Res Bull. 2018;136:118-129. doi: 10.1016/j.brainresbull.2017.02.011

Reviewed by Debjyoti Talukdar, MD, on 10/26/2021.

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