Transient impairment of olfactory threshold in acute multiple sclerosis relapse

Background: Impairment of olfactory threshold is a feature of early and active relapsing remitting multiple sclerosis (RAMS). It predicts inflammatory disease activity and was reported to be transient. However, the timing of onset and resolve of olfactory threshold impairment remains unclear. Objective: To prospectively assess the development of olfactory threshold in acute MS relapse over time in comparison to stable MS patients. Methods: In a prospective observational design, we measured olfactory threshold by performing the Sniffin' Sticks test (minimum score 0, maximum score 16 reflecting optimal olfactory function) at baseline and after 4, 12 and 24 weeks. We included 30 RRMS patients with acute MS relapse and 30 clinically stable RRMS patients (defined as no relapse within the last 12 months) as a control group. Results: Olfactory threshold was impaired in patients with acute MS relapse at baseline (median difference = -3.5; inter-quartile range [IQR] -4.5- - 2.5; p < 0.001), week 4 (-2.5; IQR -3.0 - -2.0; p < 0.001), week 12 (-1.5; IQR -2.0 - -0.5; p = 0.002) and week 24 (-0.5; IQR -1.0 - 0.0; p = 0.159) compared to stable MS patients. Of note, in relapsing patients in whom disease-modifying treatment was initiated or escalated after relapse, threshold did not differ anymore from stable patients at week 12 (-0.5; IQR -1.0 - 0.5; p = 0.247) and week 24 (0.0; IQR -1.0 - 1.0; p = 0.753). Conclusions: Olfactory threshold impairment seems to be a transient bystander feature of MS relapse. It may be correlated to the level of inflammation within the CNS and might be a useful biomarker in this regard.