Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status

Abstract

Neuromyelitis optica (NMO) is an inflammatory neurologic disease clinically characterized by severe optic neuritis (ON) and transverse myelitis (TM). The relationship between NMO and multiple sclerosis (MS) has long been a matter of debate. However, the discovery of an NMO-specific autoantibody, NMO-immunoglobulin G/aquaporin 4 (AQP4) antibody, has dramatically advanced our understanding of the disease, and the clinical, magnetic resonance imaging (MRI), optical coherence tomography, and laboratory examinations have clarified unique features of NMO that are distinct from MS. The term NMO spectrum disorders (NMOSD) incorporating spatially limited forms was introduced, as patients with recurrent or simultaneous bilateral ON or recurrent longitudinally extensive TM (LETM) alone are also often AQP4 antibody-seropositive. Moreover, studies of seropositive cases have shown that more than half of them have brain lesions, some of which are unique to NMO, and can be the onset manifestation. Some clinical features of AQP4 antibody-seronegative NMO differ from seropositive, but it remains unknown whether they are pathologically distinct. Immunosuppressive treatments are effective for acute attacks and prevention of relapses of NMOSD, and new molecularly targeted drugs are under investigation. Importantly, some disease modifying drugs for MS may exacerbate NMOSD, making early differential diagnosis of the two diseases crucial. We review the evolving clinical spectrum, the updated clinical, MRI, neuro-ophthalmological and laboratory findings, and the current status of treatment in NMOSD.

Keywords: aquaporin-4 antibody; clinical spectrum; neuromyelitis optica; treatment.

© 2013 International Society of Neuropathology.

Figures

Figure 1

Optic neuritis in neuromyelitis optica.  T1‐weighted magnetic resonance imaging of the orbital region showing an extensive lesion with marked thickening and contrast enhancement of the optic nerve (arrows).

Figure 2

Longitudinally extensive myelitis in neuromyelitis optica.  T2‐weighted hyperintense, longitudinally extensive lesion (arrows) from the cervical to the thoracic cord on the magnetic resonance imaging of a patient with recurrent myelitis and aquaporin‐4 antibodies.

Figure 3

Callosal, brainstem and cervical lesions in neuromyelitis optica spectrum disorder.  T2‐weighted hyperintense lesions (arrows) localized in the corpus callosum, brainstem and upper cervical regions on the magnetic resonance imaging of an aquaporin–4‐antibody seropositive patient with neuromyelitis optica.

Figure 4

Optic coherence tomography in neuromyelitis optica. Spectral‐domain optic coherence tomography shows severe thinning of the retinal nerve fiber layer of both eyes secondary to optic neuritis attacks. I = inferior; N = nasal; NAS = nasal; NI = nasal inferior; NS = nasal superior; OD = right eye; OS = left eye; S = superior; SUP = superior; T = temporal; TI = temporal inferior; TMP = temporal; TS = temporal superior.