Smelling the danger

Aquaporin-4 (AQP4) is widely expressed in the brain, spinal cord, and optic nerve. Its abundance in these locations and the pathogenic role of AQP4 antibodies are reflected in the inclusion of optic neuritis, acute myelitis, and brain syndromes in the most recent international consensus diagnostic criteria for neuromyelitis optica spectrum disorder (NMOSD). ¹ However, reports on the lesser established clinical manifestation of NMOSD, such as anosmia, highlighted by Marshall et al. ² in the Multiple Sclerosis Journal, are emerging. While olfactory dysfunction may manifest as an NMOSD relapse, as illustrated in this case report, the possibility of anosmia as the first and isolated presenting symptom leading to the eventual diagnosis of NMOSD is not entirely inconceivable and potentially complicates the seemingly straightforward application of the latest 2015 diagnostic criteria.

Furthermore, as pointed out by Marshall et al., ² the reported findings of cystic changes over the olfactory bulb as a result of NMOSD have been few and far between, compared to previously described similar cystic changes primarily involving the motor and visual pathways in the brain. ³ Consequently, studying serial brain magnetic resonance imaging, including dedicated evaluation of the olfactory bulb and tract, in this and similar future cases could be informative and possibly shed more light in further refining the spectrum of NMOSD and in increasing the sensitivity and specificity of its diagnostic criteria in the long run.

The natural history of NMOSD is punctuated with relapses resulting in cumulative neurological disabilities. Fortunately, there have been new emerging therapies conferring significant relapse risk reduction. Smelling the danger and prompt recognition of the expanding spectrum of clinical manifestations of NMOSD is, thus, imperative to establishing early diagnosis and employing the appropriate treatment strategies.