Olfactory dysfunction in neuromyelitis optica spectrum disorders

Abstract

Few data were available for the understanding of olfactory function in neuromyelitis optica spectrum disorders (NMOSDs). The aims of our study were to investigate the incidence of olfactory dysfunction and characterize olfactory structures, using MRI, in patients with NMOSDs. Olfactory function was evaluated by olfactometer in 49 patients with NMOSDs and 26 matched healthy controls. MRI parameters such as olfactory bulb (OB) and the olfactory-related gray matter volume changes were assessed. The frequency of olfactory dysfunction was 53% in patients with NMOSDs. Olfactory detection thresholds were positively correlated with serum aquaporin-4 antibodies (fluorescent units) tested by fluorescent immunoprecipitation assay (FIPA) in NMOSDs (p = 0.009). Patients with olfactory dysfunction had smaller OB volume than did patients without olfactory dysfunction or controls (p < 0.01). Both detection and recognition thresholds for olfaction were negatively correlated with OB volume (p = 0.018, p < 0.01). The significant gray matter volume reduction in NMOSDs was found in the bilateral piriform cortex, orbitofrontal cortex, and parahippocampal gyri (FDR correction, p < 0.05, cluster size >200 voxels). Our data suggested that olfactory function deficits are prevalent in patients with NMOSDs. Reduced OB and olfactory-related cortex volume may be responsible for the olfactory dysfunction.

Back on the scent: the olfactory system in CNS demyelinating diseases

“…Schmidt et al 48 report olfactory loss in 50% (5/10) of their NMO cohort, and Revis et al 43 found olfactory identification to be significantly more impaired in NMO than in MS. In a larger study, Zhang et al 53 observed smell dysfunction in 53% (26/49) of patients with NMO spectrum disorder. The frequency and extent to which olfactory dysfunction forms part of the clinical spectrum of other CNS demyelinating diseases, such as ADEM, myelin oligodendrocyte glycoprotein encephalomyelitis, and other immune-mediated CNS disorders, is unknown and warrants further investigation.…”

“…Olfactory bulb volume and olfactory sulcus depth have also been shown to be inversely correlated with disease duration and attack frequency in MS 54. Similarly, olfactory loss in NMO has been linked to reductions in bulb volume, alongside grey matter reduction within the piriform gyri 53. The implication of these studies is substantial.…”

“…This does not exclude the possibility that olfactory submodalities (ie, threshold, discrimination and identification) subserved by olfactory cortex may have different levels of susceptibility to injury. In NMO, the association of both anti-AQP4 seropositivity and radiological abnormalities within the olfactory bulb and cortex with olfactory dysfunction is explained by the diffuse expression of AQP-4 throughout the olfactory system 53. Involvement of the olfactory neuroepithelium in NMO cannot be precluded given expression of AQP-4 in this structure also.…”

The number of optic neuritis attacks is a potential confounder when comparing patients with NMO vs. controls by voxel-based neuroimaging analysis

“…One of these studies showed no reduction of GMV (6), which is similar to our findings in the whole patient group, even using uncorrected P values. Two other studies analyzed only GMV, with positive findings (9,10). Like our preceding comments on WMV results, studies with positive findings showed different pattern of regional GMV reduction (4,5,8–10), in four of them without correction for multiple comparisons (4,5,8,9).…”

“…Recent voxel-based morphometry (VBM) studies have shown limited reproducibility in NMO (4)(5)(6)(7)(8)(9)(10). This needs to be addressed in order to make VBM more reliable as potential imaging biomarker in this complex disease.…”