The course of neuromyelitis optica is unpredictable in most cases with more than 90% of patients experiencing relapses of optic neuritis, myelitis or both. Rest 10% of cases are associated with the concurrent course of myelitis and optic neuritis. Other symptoms include hiccups, vomiting, encephalitis, seizures, posterior reversible encephalopathy syndrome, myeloradiculitis, meningoencephalitis, hearing loss, diplopia, olfactory dysfunction, endocrinological abnormalities, pain syndromes, cognitive dysfunction, and other cranial nerve palsies. It is also associated with other autoimmune diseases (in 30-50% cases), including SLE, Sjogren’s syndrome, myasthenia gravis, autoimmune thyroid disease, and autoimmune-mediated vitamin B12 deficiency.(1)
Can Neuromyelitis Optica Be Cured?
Practically, neuromyelitis optica cannot be cured; however, the objective of the treatment is to prevent relapses and if they occur improve symptomatology of relapse, and restore the neurological functions. Since 90% of the patients experience relapses; they are treated with high dose intravenous methylprednisolone. In cases where steroid treatment is not effective, plasma exchange may be used. Plasma exchange can be considered as initial therapy if the patient has responded well to it previously. In patients with the ineffective response from both steroid and plasma exchange, intravenous immunoglobulin or cyclophosphamide can be considered.(1)
Patients with neuromyelitis optica have to undergo long term therapy for immunosuppression. Immunosuppressives include therapies targeting B cells, such as intravenous rituximab or oral azathioprine and prednisone. Other treatment options include mycophenolate mofetil, methotrexate, and mitoxantrone. It is important to note that, interferon-beta that is widely used in the management of multiple sclerosis, is not indicated in the management of neuromyelitis optica as it has been known to aggravate the symptoms rendering it ineffective in its management.(1)
Neuromyelitis optica, also known as Devic’s syndrome or neuromyelitis optica spectrum disorder, is an inflammatory disease affecting the central nervous system characterized by relapses of optic neuritis or myelitis. The humoral immune system has long been suggested in the disease pathogenesis and after the detection of disease-specific serum immunoglobulin G autoantibody that targets the astrocytic water channel aquaporin-4; it is clear that neuromyelitis optica is a clearly separate entity from multiple sclerosis. NMO-IgG/AQP4 antibodies are present in about 80% of the patients with neuromyelitis optica. Although there is overlap in the symptoms and other paraclinical findings of neuromyelitis optica and multiple sclerosis, neuromyelitis optica is considered an autoimmune condition that has different pathogenesis from that of multiple sclerosis.(1)
There are various clinical, pathological and immunological evidence that indicate the association of AQP4 antibodies in the pathogenesis of neuromyelitis optica. AQP4 is mostly expressed in the opticospinal tissues and an immune response involving optic nerve and spinal cord can explain higher symptoms and association of these sites. Similarly, disease-specific several studies have correlated the disease activity of neuromyelitis optica and increased serum levels of the antibody before relapse and declining levels at the time of recovery. In patients with isolated optic neuritis or with isolated longitudinally extensive transverse myelitis, the presence of AQP4 antibodies is related to increased development of neuromyelitis optica. The presence of this antibody also predicts the course of future relapses. Furthermore, the seropositivity is also related to the severity of the disease and more extensive involvement of the spinal cord, optic and motor disability along with severity in the long term disability course.(1)
It is noteworthy, that most of the patients with AQP4 antibodies are females with a female to male ratio of 10:1 and it is often associated with the more relapsing course than seronegative patients. It is also noted that successful treatment is associated with a decrease in the serum levels of the AQP4 antibodies. Additionally, B cell or antibody-targeted treatments, such as plasma exchange, rituximab, and tocilizumab are effective in neuromyelitis optica and incomplete B cell depletion and recurrence of B cells have been associated with severe attacks.(1)
Apart from AQP4 antibodies, there are other immunological mediators associated with neuromyelitis optica that includes macrophages, eosinophils, neutrophils, proinflammatory cytokines (IL-6, CXCL13, BAFF), B cells, T cells, glutamate-mediated excitotoxicity along with IgG and IgM deposits in neuromyelitis optica lesions.