Neuromyelitis optica (NMO), also called Devic disease, is an inflammatory CNS disorder that is associated with serum aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies. NMO is characterized by severe attacks of optic neuritis and longitudinally extensive transverse myelitis. NMO represents a rare cause of inflammatory white matter disease in North America; however, it accounts for almost 50% of demyelinating disorders in Asia and the West Indies. NMO can be differentiated from MS by its distinct clinical, radiographic, pathologic, and serologic features. NMO is associated with severe visual impairment; early diagnosis and aggressive treatment are important for the best chance of preserving visual and neurologic function.
Clinical presentation of neuromyelitis optica
Optic neuritis, the classic ophthalmic manifestation of NMO, is typically severe (visual acuity <20/200) and is associated with poor visual recovery. Bilateral visual symptoms, recurrent optic neuritis, poor visual outcomes, or concurrent autoimmune disease should raise a concern for NMO-related optic neuritis (see Chapter 4).
NMO may involve the optic chiasm and tracts, resulting in bitemporal or homonymous hemianopic visual field defects. Eye movement disorders such as nystagmus (upbeat, downbeat, or mixed horizontal-torsional), internuclear ophthalmoplegia, and opsoclonus can develop secondary to brainstem lesions.
Table 14-1 Disease-Modifying Therapies Used in the Treatment of Multiple Sclerosis
Figure 14-2 Proposed screening protocol for fingolimod-associated macular edema (FAME). Patients with visual symptoms at any time during treatment should have an additional eye examination, particularly during the initial months of treatment. DFE = dilated fundus exam; FA = fluorescein angiography; ME = macular edema; MS = multiple sclerosis; OCT = optical coherence tomography.
(Adapted from Jain N, Bhatti MT. Macular edema associated with fingolimod. EyeNet. 2012: 43–44.)
Patients with transverse myelitis may present with weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional sphincter activities, or dysfunction of the autonomic nervous system. NMO is a central cause of refractory hiccups and vomiting due to caudal medullary lesions (the area postrema and the nucleus tractus solitarius).
Diagnosis of neuromyelitis optica
The development of the NMO-IgG (AQP4-IgG antibody) test has drastically improved our ability to diagnose NMO. However, the test is negative in approximately 25% of patients. In 2015, an international panel published revised diagnostic criteria for NMO and also recommended unifying NMO and related syndromes under the new nomenclature of neuromyelitis optica spectrum disorder (NMOSD) (see Chapter 4, Table 4-5, for criteria in diagnosing NMOSD).
CSF findings suggestive of NMO include a pleocytosis greater than 50 cells per microliter, a high percentage of polymorphonuclear cells, or the presence of eosinophils. In rare instances, CSF AQP4-IgG has been detected in seronegative patients.
Conventional MRI shows typical changes resulting from acute optic neuritis with NMO, including optic nerve enlargement and enhancement, as well as increased T2 signal. These changes, which are often more longitudinally extensive than in MS, are frequently bilateral and may involve the optic chiasm and tracts. Brain MRI abnormalities at onset have been reported in 43%–70% of patients with NMOSD. NMO lesions are typically found in the areas surrounding the third ventricle and the cerebral aqueduct (which include the thalamus, hypothalamus, and anterior border of the midbrain), as well as the dorsal brainstem adjacent to the fourth ventricle and the corpus callosum. Extensive and confluent hemispheric white matter lesions can also be seen, occasionally mimicking posterior reversible encephalopathy syndrome (PRES; discussed later). Spinal cord MRI typically shows contiguous T2-weighted signal abnormality extending over 3 or more vertebral segments.
Kim HJ, Paul F, Lana-Peixoto MA, et al. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology. 2015;84(11):1165–1173.
Wingerchuk DM, Banwell B, Bennett JL, et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177–189.
Treatment of neuromyelitis optica
NMO treatment includes managing acute attacks and preventing future exacerbations. For patients experiencing an acute attack, intravenous methylprednisolone therapy (1000 mg daily for 3–5 days) remains the first-line therapy. If there is no significant clinical improvement on corticosteroids, plasma exchange has been shown to be effective and should be considered. Intravenous immunoglobulin (IVIg) has also been used to treat acute NMO exacerbations and prevent relapses. Immunosuppressive therapy (eg, azathioprine, mycophenolate, or rituximab) is generally instituted after the initial attack to lower the frequency and severity of future exacerbations. Several disease-modifying agents frequently used for treatment of MS (eg, interferon-beta, natalizumab, and fingolimod) may increase the relapse rate in patients with NMO. This phenomenon likely reflects the different immunobiology of these conditions, emphasizing the importance of accurate diagnosis in guiding optimal treatment decisions.
Kowarik MC, Soltys J, Bennett JL. The treatment of neuromyelitis optica. J Neuroophthalmol. 2014;34(1):70–82.
Sato DK, Lana-Peixoto MA, Fujihara K, deSeze J. Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol. 2013;23(6): 647–660.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.