Neuromyelitis Optica Spectrum Disorder (NMOSD)


Neuromyelitis optica spectrum disorder (NMOSD) is a chronic demyelinating disease of the central nervous system (CNS) in which recurrent attacks affect predominantly the optic nerves, spinal cord, and area postrema. NMOSD was once considered a phenotypic variant of multiple sclerosis (MS). However, since the discovery of highly specific NMO immunoglobulin G (NMO-IgG) autoantibodies against aquaporin-4 (AQP4), which are found in the serum of some affected patients, NMOSD has been recognized as an immunologically distinct entity, separate from MS.1 In 2015, the International Panel for NMO Diagnosis advocated that the term NMOSD be used for a condition characterized by selective demyelination of the spinal cord and optic nerves. To facilitate an early and more precise diagnosis, the International Panel formulated specific criteria for patients with AQP4 antibody seropositivity or seronegativity who presented with optic neuritis, transverse myelitis, or area postrema syndrome accompanied by a medullary lesion on magnetic resonance imaging (MRI).2 

The international Panel for NMO Diagnosis criteria for a diagnosis of NMOSD specify core clinical characteristics.2 These include the following: (1) optic neuritis; (2) acute myelitis; (3) area postrema syndrome; (4) acute brainstem syndrome; (5) symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic lesions on MRI; and (6) symptomatic cerebral syndrome with NMOSD-typical brain lesions.3 In more than 90% of cases, NMOSD is a relapsing disorder in which outbreaks of optic neuritis, myelitis, or both can appear at any time.4 

Clinical Features Due to Optic Nerve Involvement

Optic neuritis, the most common initial symptom, is a painful inflammation of the optic nerve that can be unilateral or bilateral. It leads to reduced visual acuity in the affected eye. Within 5 years after onset, 50% of patients lose functional vision. A prodromal upper respiratory illness may or may not precede NMOSD.2,5 

Clinical Features Due to Spinal Cord Involvement

Transverse myelitis, in which both sides of a section of the spinal cord are inflamed, is a feature of NMOSD. The symptoms affect some, if not all, motor, sensory, and autonomic function (bowel and bladder) below a specific level of the body; however, symptoms can be unilateral.5 Myelitis usually affects more than 3 segments of the spinal cord. Sensory effects include numbness, dysesthesia, pain, and tonic spasms along with neuropathic pruritus and sudden sensorineural hearing loss. Patients frequently experience urinary dysfunction with spinal cord lesions.2 Limb pain, back pain, neck stiffness, mild to severe paraparesis, paraplegia of the lower limbs, loss of bowel and bladder control, and sensory loss may also occur. The deep tendon reflexes may at first be increased, reduced, or missing, then become accelerated. The disease can be difficult to distinguish from idiopathic transverse myelitis.5

Most deaths in patients with NMOSD are caused by a severe form of ascending cervical myelitis or brainstem involvement, which results in respiratory failure.4

Clinical Features Due to Area Postrema, Brain Stem, and Diencephalic Involvement

Symptoms such as severe nausea, vomiting, and hiccups occur as a result of involvement of the area postrema of the medulla, as well as the nucleus solitarius, ventrolateral respiratory center, and nucleus ambiguus. Intractable vomiting is the first symptom noted in up to 12% of AQP-4 seropositive cases. Atypical features include asymptomatic transitory increases in creatine kinase levels. Hypersomnia and narcolepsy can be the initial symptoms in patients with involvement of the hypothalamus and the temporal lobe. Hyperthermia and galactorrhea may also occur if the hypothalamus is involved.2

Other Symptoms

Headache can be another initial symptom of the disease and can be due to a variety of factors. Patients with NMOSD also have a higher risk for seizures. NMOSD may be linked to psychological changes. Cognitive abnormalities such as depression, impairment, and suicidal tendencies have been seen. These criteria are also applicable for pediatric patients.2 

References

  1. Matsushita T, Masaki K, Isobe N, et al. Genetic factors for susceptibility to and manifestations of neuromyelitis optica. Ann Clin Transl Neurol. 2020;7(11):2082-2093. doi:10.1002/acn3.51147
  2. ​​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
  3. ​​Weinshenker BG, Wingerchuk DM. Neuromyelitis spectrum disorders. Mayo Clin Proc. 2017;92(4):663-679. doi:10.1016/j.mayocp.2016.12.014
  4. Jarius S, Wildemann B, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin Exp Immunol. 2014;176(2):149-164. doi:10.1111/cei.12271
  5. Neuromyelitis optica spectrum disorder. National Organization for Rare Disorders (NORD). Accessed October 21, 2021.

Reviewed by Debjyoti Talukdar, MD, on 10/23/2021.

Reviewed by Debjyoti Talukdar, MD, on 10/23/2021.

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