Differential Olfactory Dysfunction Indicates Inflammation and Network Degeneration in Multiple Sclerosis

Olfactory Dysfunction in MS

Abstract

Objective: Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system. Although olfactory dysfunction in MS has been investigated for decades, systematic assessment remains limited. This study aimed to evaluate olfactory function in people with MS (PwMS) in relation to clinical parameters and magnetic resonance imaging (MRI) plaque distribution, using the Sniffin’ Sticks test.
Methods: Twenty-eight patients with MS, one participant with clinically isolated syndrome (22 women, 75.9%), and 27 healthy controls were included. Participants with primary olfactory disorders were excluded. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Plaque locations on brain MRI scans were recorded. The Sniffin’ Sticks test was performed, and threshold, discrimination, identification, and total threshold + discrimination + identification (TDI) scores were obtained for each participant.
Results: Threshold, identification, and TDI scores were significantly lower in PwMS than in controls (p = 0.021, 0.004, and 0.005, respectively). Discrimination, identification, and TDI scores were significantly correlated with age (p = 0.001, 0.048, and 0.004, respectively) and with disease duration (p = 0.001, 0.028, and 0.001, respectively). Olfactory performance was unrelated to sex, smoking, clinical classification, EDSS, or MRI plaque distribution (all p > 0.05). A progressive disease course did not influence olfactory measures (p > 0.05).
Conclusion: Olfactory dysfunction can be observed across MS subtypes and becomes more pronounced with increasing age and longer disease duration. Threshold impairment may reflect inflammatory activity, whereas reductions in identification and TDI scores likely indicate cumulative neurodegeneration. Multidimensional olfactory testing is simple, accessible, and low-cost. Our findings support its use as a non-invasive complementary biomarker for monitoring long-term neurodegenerative processes in MS.