Chapter 193: Neuromyelitis Optica

Neuromyelitis optica (NMO; Devic’s disease) is an aggressive inflammatory disorder characterized by recurrent attacks of optic neuritis (ON) and myelitis; the more inclusive term NMO Spectrum Disorders (NMOSD) incorporates pts with partial forms, and with involvement of additional CNS structures ( Table 193-1 ). NMO is more frequent in women than men (>3:1), and typically begins in adulthood but can arise at any age. An important consideration is distinguishing between NMO and multiple sclerosis (MS; Chap. 192: Multiple Sclerosis ). In NMO, attacks of ON can be bilateral and produce severe visual loss (uncommon in MS); myelitis can be severe and transverse (rare in MS) and is typically longitudinally extensive ( Fig. 193-1 ) involving three or more contiguous vertebral segments. Also in contrast to MS, progressive symptoms typically do not occur in NMO.

FIGURE 193-1
Imaging findings in neuromyelitis optica: longitudinally extensive transverse myelitis, optic neuritis and brainstem involvement. (A) Sagittal fluid attenuation inversion recovery (FLAIR) cervical-spine magnetic resonance image (MRI) showing an area of increased signal change on T2-weighted imaging spanning more than 3 vertebral segments in length. (B) Sagittal T1-weighted cervical-spine MRI following gadolinium-DPTA infusion showing enhancement. (C) Coronal brain MRI shows hyperintense signal on FLAIR imaging within the left optic nerve. (D) Coronal T1-weighted brain MRI following gadolinium-DPTA infusion shows enhancement of the left optic nerve. (E) Axial brain MRI shows an area of hyperintense signal on T2-weighted imaging within the area postrema (arrows). (F) Axial T1-weighted brain MRI following gadolinium-diethylene triamine pentaacetic acid (DPTA) infusion shows punctate enhancement of the area postrema (arrows).
TABLE 193-1: Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder
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 (cell-based assay strongly recommended)
  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:
    1. At least 1 core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome
    2. Dissemination in space (2 or more different clinical characteristics)
    3. Fulfillment of additional MRI requirements, as applicable
  2. Negative test 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 or 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 of 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 ≥3 contiguous segments (LETM) OR ≥3 contiguous segments of focal spinal cord atrophy in pts with history compatible with acute myelitis
  3. Area postrema syndrome requires associated dorsal medulla/area postrema lesions
  4. Acute brainstem syndrome requires periependymal brainstem lesions
Abbreviations: AQP-4, aquaporin-4; LETM, longitudinally extensive transverse myelitis; MRI, magnetic resonance imaging; NMOSD, neuromyelitis optica spectrum disorder.
Source: Adapted from Wingerchuk DM et al: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189, 2015. Used with permission.

Brain MRI may be normal or show areas of nonspecific signal change as well as lesions associated with specific syndromes such as the hypothalamus causing an endocrinopathy; the lower medulla presenting as intractable hiccoughs or vomiting; or cerebral hemispheres producing focal symptoms, encephalopathy, or seizures. Large MRI lesions in the cerebral hemispheres may have a “cloud-like” appearance and, unlike MS lesions, are often not destructive and can resolve completely. Spinal cord MRI lesions typically consist of focal enhancing areas of swelling and tissue destruction, extending over three or more spinal cord segments, and on axial sequences, these are centered on the gray matter of the cord. CSF findings include pleocytosis greater than in MS, with neutrophils and eosinophils in many acute cases; oligoclonal bands are uncommon.

NMO is an autoimmune disease associated with a highly specific autoantibody directed against the water channel protein aquaporin-4 (AQP4) that is present in the sera of approximately 70% of pts with a clinical diagnosis of NMO. AQP4 is localized to the foot processes of astrocytes. Pathology reveals inflammation, loss of astrocytes, and an absence of staining of AQP4 by immunohistochemistry, plus thickened blood vessel walls, demyelination, and deposition of antibody and complement.

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