The acronym Neuromyelitis Optica Spectrum Disorder began to be applied clinically in the past 10 years. For many decades the also called Devic Disease was considered part of Multiple Sclerosis. The identification of a separate disease altogether started with the discovery of aquaporin in 1986, and then of anti-aquaporin 4 immunoglobulin G. This antibody to the aquaporin receptor was measured in a blood test, which was positive initially in a limited set of patients. While the clinical, radiologic and pathologic features of these patients was established, many more patients had their bloods tested. Specifically, patients with severe optic nerve and spinal cord lesions. This led to an increase in the pool of patients who were clinically and radiologically similar. But many did not have the antibody in their blood, so they were called seronegative neuromyelitis optica. Some of these went on to be found to have other antibodies in their blood, as anti-MOG and anti-NF.
Since 2015 patients began to be diagnosed as Neuromyelitis Optica Spectrum Disorder when they had a core of clinical features, including severe, progressive optic neuritis, spinal cord lesions and area postrema syndrome, with florid imaging evidence of inflammation, and slow, partial recovery. Patients have recurrent severe attacks with poor recovery. Pathology shows extensive death of tissue, including of oligodendrocytes, demyelination and axonal injury. Contrary to multiple sclerosis, there are more attacks during pregnancy, and the postpartum period is of high risk.
Klaviter et al. Neurology 2017, 89:2238-2244
Treatment with intense immune suppression started off with azathioprine, and moved on to cyclophosphamide and rituximab, due to 25-60% of patients not responding. We have been using the same high dose regimen of cyclophosphamide for many years with a high degree of success in some patients. But this is a very difficult clinical situation, many patients abandon treatment as soon as they have some improvement. In view of intense immune suppression, many have fatal complications when they attempt to be cared for in general neurology or general medicine environments. It is a group of patients with bad prognosis.
Recently thirteen patients with neuromyelitis optica spectrum disorder underwent successful stem cell therapy in the USA. It included stem cell mobilization with cyclophosphamide 2g/m2 and then imune non-ablative therapy with unselected peripheral blood stem cels, cyclophosphamide 200mg/kg, thymoglobulin 6mg/kg, and rituximab 1000mg IV. These total doses were given in an open label prospective cohort fashion. At 57 months medium follow up one patient had died at 10 months due to complications of co-existing systemic lupus erythematosus; 11 are more than 5 years post-transplant, 80% without disease relapse. Extended disability score (EDSS) improved from 4.4 to 3.3 points. 9 patients became seronegative and none of these relapsed.
RK Burt et al. Neurology 2019, 93:e1732-e1741
This is a marvellous result, and possibly reflects the fact that it is a one-off therapy that satisfies these families, who are not prepared to a long inglorious losing war, in which great financial and emotional resources appear to them to be rapidly thrown away, while their patient loses vision and movement.
PA Muraro and JA Cohen. Neurology 2019, 93:776-777
Dr Paulo Bittencourt
