Neuromyelitis Optica Spectrum Disorder (NMOSD)


Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system (CNS) inflammatory disorder caused by an immune response. It is identified by coexistent inflammation and demyelination of the optic nerve and spinal cord, causing optic neuritis and myelitis, respectively. Several studies have found that the prevalence and clinical and demographic characteristics of the disease vary by population.1 NMOSD resembles the clinical course of multiple sclerosis (MS) due to its relapsing and remitting pattern of myelitis and optic neuritis; however, the distinctions between the conditions were outlined in the late 1990s, and subsequent diagnostic criteria allowed for precise clinical and radiological differentiation between the 2 diseases. The discovery of a pathogenic autoantibody biomarker, AQP4-IgG, an immunoglobulin (Ig) targeting aquaporin-4 (AQP4), in the serum of affected patients recognized NMOSD as an immunologically distinct entity, transformed the disease diagnosis, and influenced its therapeutic development.2 

Complications of NMOSD include visual field defects and motor impairment, leading to blindness and permanent motor disabilities. Myogenic respiratory failure causes higher rates of mortality in severe forms of the disease.3

Severe Visual Impairment and Blindness 

The visual impairment in patients with relapsing forms of NMOSD is more severe than that in patients with other forms of the disease. It has been observed that vision loss occurs in the first eye within the first 2 years of disease onset and in the second eye within 13 years.4 Scotoma, a visual field defect, has been linked to MS and NMOSD. Central scotoma has been noted more frequently in MS cases, while noncentral scotoma is more common in NMOSD cases. Later, these patients develop altitudinal hemianopia.4 In both AQP4-IgG-positive and myelin oligodendrocyte glycoprotein (MOG-IgG)-positive NMOSD cases, both eyes are impaired in the long run.5

Sensory Impairment

Sensory symptoms range from mild in nature to severe sensorimotor spastic tetraparesis in patients with transverse myelitis (TM). Symptoms usually start in the feet and progress to a “sensory level” on the trunk, and they are commonly preceded by pain at the lesion site.5 

TM may also result in bladder, bowel, and erectile dysfunction. Symptoms such as overactive bladder and retention of urine lead to catheterization, thus affecting patients’ quality of life.5 

CNS Complications 

Both AQP4-IgG-positive and MOG-IgG-positive NMOSD cases impact the brainstem, and spinal cord lesions frequently extend into the medulla oblongata.5

Epileptic seizures, psychiatric ailments like depression and encephalopathic features, and neuropsychological imbalances including reduced attention and memory are classic symptoms linked to brain involvement.5

During the course of illness, some individuals develop signs of cerebral syndrome. Symptoms include confusion, seizures, aphasia, apraxia, cognitive decline, and posterior reversible encephalopathy syndrome (PRES), among others.4

Pain

Patients with NMOSD experience pain and dysesthesia, which can be debilitating.5

Painful tonic spasms that might be misinterpreted as spasticity typically accompany or follow myelitis.5 Retro-orbital pain is a prevalent pain syndrome induced by optic neuritis in NMOSD cases.4

Respiratory Failure 

Hiccups and respiratory failure are common clinical myelitis-related episodes in NMOSD. Severe myelitis-related respiratory failure causing mortality has been observed in one-third of relapsing NMOSD patients, which is usually seen early in the disease course.6

Extra-CNS Complications

Myositis, internal otitis, gastritis, and vitamin B12 deficiency have all been mentioned as probable extra-CNS consequences of AQP4-IgG-related autoimmunity due to AQP4 expression outside of the CNS. Furthermore, AQP4-IgG-positive NMOSD is frequently linked to other autoimmune disorders, such as systemic lupus erythematosus, Sjögren syndrome, antiphospholipid syndrome, rheumatoid arthritis, myasthenia gravis, and celiac disease. The existence of these comorbidities might affect the clinical picture and should be considered when treating patients with NMOSD.5

References

  1. Zarei S, Eggert J, Franqui-Dominguez L, et al. Comprehensive review of neuromyelitis optica and clinical characteristics of neuromyelitis optica patients in Puerto Rico. Surg Neurol Int. 2018;9:242. doi:10.4103/sni.sni_224_18
  2. Weinshenker BG, Wingerchuk DM. Neuromyelitis spectrum disorders. Mayo Clin Proc. 2017;92(4):663-679. doi:10.1016/j.mayocp.2016.12.014
  3. Shumway CL, Patel BC, De Jesus O. Neuromyelitis optica (NMO, Devics disease). In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2021. Accessed November 1, 2021.
  4. Ramakrishnan P, Nagarajan D. Neuromyelitis optica spectrum disorder: an overview. Acta Neurobiol Exp (Wars). 2020;80(3):256-272.
  5. Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers. 2020;6(1):85. doi:10.1038/s41572-020-0214-9
  6. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica (Devic’s syndrome). Handb Clin Neurol. 2014;122:581-599. doi:10.1016/B978-0-444-52001-2.00025-X

Reviewed by Debjyoti Talukdar, MD, on 10/30/2021.

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