Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is a rare immune-mediated inflammatory disorder of the CNS, characterized by concurrent inflammation and demyelination of the optic nerve and the spinal cord.
Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is a rare immune-mediated inflammatory disorder of the CNS, characterized by concurrent inflammation and demyelination of the optic nerve and the spinal cord.
History:
The term neuromyelitis optica (derived from neuro-myélite optique aiguë) was first described by Eugène Devic and his doctoral student Fernand Gault in 1894. The disease was therefore previously referred to as Devic’s disease. Until recently it was unclear whether neuromyelitis optica was a separate disease or merely a more severe form of ‘optico-spinal’ multiple sclerosis (MS). It was not until 2004 when the putative antigenic target, the aquaporin-4 water channel was identified, and the two diseases could be reliably distinguished through the detection of AQP4-Abs. The latest iteration of diagnostic guidelines unify antibody-negative and positive forms under the umbrella of NMOSDs.
Presentation
Classic presentations:
In more than 90% of patients, NMO is a relapsing disease with attacks of ON, myelitis or both, occurring unpredictably
Myelitis (spinal cord inflammation)
Severe optic neuritis
Area postrema syndrome (bouts of intractable vomiting and hiccoughs)
International diagnostic criteria for neuromyelitis optica spectrum disorder (2015):
International Panel for Neuromyelitis Optica Diagnosis Neuromyelitis Optica Spectrum Disorders Diagnostic Criteria for adult patients | Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85:177–89.
Neuroimaging:
Spinal cord and optic nerve MRI patterns in neuromyelitis optica spectrum disorder: Spinal cord imaging in the context of acute myelitis in neuromyelitis optica spectrum disorders (NMOSD) usually reveals a longitudinally extensive transverse myelitis (LETM) lesion extending over 3 or more vertebral segments. Sagittal T2-weighted MRI of the thoracic spinal cord (A) demonstrates a typical LETM lesion involving most of the thoracic spinal cord (arrows). LETM lesions have a predilection for the central cord, as shown by axial T2-weighted (B; arrowhead) and T1-weighted MRI with gadolinium (C; arrowhead). Cervical LETM may extend into the medulla, a characteristic NMOSD pattern demonstrated in D (arrows; sagittal T2-weighted MRI) and E (arrows; sagittal T1-weighted MRI with gadolinium). Acute LETM lesions can be associated with intralesional hypointensity as shown by sagittal T1-weighted MRI (F; arrow); in this example, a rim of gadolinium enhancement surrounds the hypointense region. Chronic sequelae of LETM may include longitudinally extensive segments of spinal cord atrophy as shown by T2-weighted MRI using sagittal (G; the 2 arrowheads indicate the atrophic segment and the top arrow indicates the normal diameter of unaffected cervical spinal cord) and axial planes (H; arrowhead shows an atrophic spinal cord). Fast spin echo fat-suppressed T2-weighted MRI in the axial (I) and coronal (J) planes shows increased signal throughout most the length of the left optic nerve, especially its posterior portion (arrows). Axial T1-weighted MRI with gadolinium shows enhancement of the optic chiasm (K; arrows). These images are from 2 different patients experiencing acute optic neuritis in the setting of NMOSD. | Wingerchuk, D. M., Banwell, B., Bennett, J. L., Cabre, P., Carroll, W., Chitnis, T., de Seze, J., Fujihara, K., Greenberg, B., Jacob, A., Jarius, S., Lana-Peixoto, M., Levy, M., Simon, J. H., Tenembaum, S., Traboulsee, A. L., Waters, P., Wellik, K. E., Weinshenker, B. G., & International Panel for NMO Diagnosis (2015). International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology, 85(2), 177–189. https://doi.org/10.1212/WNL.0000000000001729
Management
Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack.
Acute management:
When a diagnosis of NMO is confirmed or suspected, any acute exacerbation should ideally be treated promptly with a high dose of IVMP for 3–5 days
Proposed management algorithm for acute attacks in patients with a diagnosis of NMOSD according to the IPND criteria or of MOG-IgG-associated disease. | Jarius, S., Paul, F., Weinshenker, B.G. et al. Neuromyelitis optica. Nat Rev Dis Primers 6, 85 (2020). https://doi.org/10.1038/s41572-020-0214-9
Chronic management:
As NMO takes a relapsing course in most cases, with incomplete recovery and rapid accumulation of neurological deficits, immunosuppressive treatment should be initiated after initial treatment.
Azathioprine (AZA): DNA intercalation on inhibition of de novo purine synthesis
Rituximab therapy (RTX): Anti-CD20, a depletion of B-cells and plasmablasts (chimeric monoclonal antibody [mAb])
Mycophenolate mofetil (MMF): Inhibition of inosine monophosphate dehydrogenase (de novo guanosine synthesis)
Proposed long-term management of patients with NMOSD according to the IPND criteria except MOG-IgG-positive cases. | Jarius, S., Paul, F., Weinshenker, B.G. et al. Neuromyelitis optica. Nat Rev Dis Primers 6, 85 (2020). https://doi.org/10.1038/s41572-020-0214-9
