Epidemiology and Clinical Features of NMOSD in Australia and New Zealand

Abstract

Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions predominantly in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes, is thought to be causative. A clinic and laboratory-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand was undertaken to establish incidence and prevalence across the region and in populations of differing ancestry. Patients with clinical and laboratory features that were suspicious for NMOSD were referred to me. Testing for NMO antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence based on additional laboratory identified cases. The capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100,000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100,000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100,000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. These figures are comparable with figures from other populations of largely European ancestry. I found NMOSD to be more common in the population with Asian ancestry.Frequencies of self-determined ethnic ancestry were calculated for confirmed NMOSD, suspected NMOSD, and MS. Prevalence rates for NMOSD and MS according to ancestry were compared. NMOSD cases were more likely to have Asian, Indigenous, or Other ancestry compared to suspected NMOSD or MS. There were no differences in the clinical phenotype of NMOSD seen in Indigenous compared to European ancestry populations. Per 100,000, the prevalence estimate for NMOSD in people with Māori ancestry was 1.50 (95% CI 0.52–2.49), which was similar to those with Asian ancestry 1.57 (95% CI 1.15–1.98). NMOSD prevalence in Australian Aboriginal and Torres Strait Islander populations was 0.38 (95% CI 0.00–0.80) per 100,000. I found the prevalence of NMOSD in the Māori population was similar to South East Asian countries, reflecting their historical origins. The prevalence of MS in this group is intermediate between those with South East Asian and European ancestry living in New Zealand. Both NMOSD and particularly MS appear to be uncommon in the Indigenous populations of Australia. In collaboration with laboratory scientists, I compared five different assays for antibodies to aquaporin-4 in cases of NMOSD and controls to assess their relative utility. All aquaporin-4 antibody assays proved to be highly specific. Sensitivities ranged from 60 to 94%, with cell-based assays having the highest sensitivity. Antibodies to MOG were detected in 8/79 (10%) of the residual suspected cases of NMOSD. Under the 2015 IPND diagnostic criteria for NMOSD, cell-based assays for aquaporin-4 are sensitive and highly specific, performing better than tissue-based and ELISA assays. A fixed cell-based assay showed near-identical results to a live-cell based assay. Antibodies to MOG account for only a small number of suspected NMOSD cases (8/177 [5%]).When compared to multiple sclerosis (MS), age at onset, relapse rates and disability levels (EDSS) were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD, whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in two thirds of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. I have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. I have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD. This group remain a diagnostic challenge