Neuromyelitis Optica (Devic’s Disease): A New Concept for an Old Disease

Abstract

Neuromyelitis optica (NMO) is a central nervous system disease, characterized by demyelination, necrosis and inflammation. The disease was described by Eugene Devic and Fernand Gault in the late nineteenth century and was defined as a monophasic fulminant disease caused by inflammation of the spinal cord (myelitis) and the optic nerve (optic neuritis, ON) at the same time. For almost a century, the disease that was later named after Devic was considered as previously defined: an infrequent monophasic form of multiple sclerosis (MS), even though atypical cases including that with relapsing course were reported in the first decades of the twentieth century. It has since then been revealed those the relapsing form is the more frequent one, being responsible for almost 80 % of the cases; however, relapses can characteristically occur within a short period of time, in ‘clusters’. Affection of CNS areas beside the optic nerve and spinal cord has been also well established by clinical, pathological and neuroimaging data. In 2004, a specific IgG was isolated from the sera of patients, which was named NMO-IgG. The target of the antibody soon became identified, which proved to be the main water channel of the central nervous system (CNS), the aquaporin-4 (AQP4) molecule. This resulted in a reclassification of NMO as one of the antibody-mediated channelopathies, which fundamentally changed the concept of its therapy as well. Though NMO is an autoimmune inflammatory demyelinating disease of the CNS, its pathogenesis is more reminiscent of myasthenia gravis (MG), the antibody-mediated channelopathy of the neuromuscular junction. NMO is not always associated with the presence of anti-AQP4 antibody, seronegative forms are also known; however, similar to MG, pathogenic role of additional antibodies can be suspected. Indeed, antibodies against myeline oligodendrocyte glycoprotein (MOG) have been recently detected in the sera of patients with AQP4-seronegative NMO. According to the present international diagnostic classification, both optic neuritis and myelitis are required for the diagnosis of NMO. The diagnosis and therapy is however, complicated by the atypical or abortive forms, which are also referred to as NMO spectrum diseases (NMO-SD). The most important forms among them include the ‘spatially limited’ forms, in which the two main CNS targets, the optic nerve and the spinal cord are differentially involved: (i) the recurrent isolated optic neuritis (RION) or the bilateral optic neuritis (BON) without myelitis, as well as (ii) the longitudinally extensive transverse myelitis (LETM) with a typical MRI appearance of T2 hyperintense signal with a length ≥3 vertebral segments. The spatially limited spectrum diseases can convert into definite NMO in case the missing symptom appears during a consequent relapse. This, however, can take years or even decades. The clinical complexity and the rapid increase in the knowledge have promoted several recent international guidelines and consensus papers. Considering the problem of NMO-SD, a novel international classification and consensus diagnostic criteria of NMO is also under way.