Diagnosis and management of neuromyelitis optica spectrum disorders - An update

Highlights

• The neuromyelitis optica (NMO) spectrum disorders include NMO and atypical presentations.

• NMO spectrum disorders (NMOSD) are characterized by antibodies targeting aquaporins.

• MRI imaging associated with aquaporin-4 immunoglobulin G (AQP4 IgG) evaluation allows differential diagnosis.

• Current treatment is based on steroids and other immunosuppressive drugs.

• Novel biological agents will be available in the near future.

Abstract

Neuromyelitis optica (NMO) and Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune conditions characterized by inflammatory involvement of the optic nerve, spinal cord and central nervous system. Novel evidence showed a key role of autoantibodies against aquaporin-4 immunoglobulin G (AQP4 IgG) in the pathogenesis of NMOSD and, recently, new classification and diagnostic criteria have been adopted to facilitate an earlier identification and improve the management of these conditions. Diagnosis of NMOSD is currently based on clinical, neuroimaging and laboratory features. Standard treatment is based on the use of steroids and immunosuppressive drugs and aims to control the severity of acute attacks and to prevent relapses of the disease. This review gives an update of latest knowledge of NMOSD and NMO, emphasizing the novel diagnostic criteria and both current and future therapeutic approaches.

Introduction

Neuromyelitis optica spectrum disorders (NMOSD), that include the neuromyelitis optica (NMO), previously known as Devic's syndrome, are a group of inflammatory disorders of the central nervous system (CNS) characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord.

The term “NMO spectrum disorders” (NMOSD) has been recently introduced to expand the definition of NMO and to include a wider spectrum of clinical manifestations [1,2]. In fact, the increasing understanding of the pathogenesis of these disorders, the identification of disease-specific serum NMO-IgG antibodies, that selectively bind aquaporin-4 (AQP4), and the definition of specific neuroimaging features of NMO resulted in the revision of the previous classification of NMO, redefined as NMOSD, with more specific diagnostic criteria and an update in the guidelines for disease management [[3], [4], [5], [6]]. These clinical, immunological and radiological features allow a proper differential diagnosis between NMO and multiple sclerosis (MS), or autoimmune diseases [[7], [8], [9]]. Beside NMOSD with AQP4-IgG (NMOSD-AQP4), the novel classification has defined a group of NMOSD without AQP4-IgG or with unknown AQP4-IgG status that includes patients with atypical manifestations such as unilateral optic neuritis (ON), isolated or recurrent transverse myelitis, or isolated brain lesions with or without detectable anti AQP4-IgG autoantibody [10].

NMO is usually sporadic but a few familial cases have been described [11]. NMO is a rare disease (ORPHA:71211) that affects all ethnicities in different socio-economic environments, with a prevalence in ranging from 0.52 to 4.4/100000 in different studies [[12], [13], [14], [15], [16]]. Overall, the wide range of prevalence reported for NMO is due to variability in the source data, as well as to the different diagnostic criteria and assay used to test the AQP4-IgG.

The aim of the present review is to describe clinical features of NMO and NMOSD and to provide an update on the novel classification, diagnostic criteria, and the current therapeutic approach.