“Who ‘nose’ when a seizure will happen?” Prodromal olfactory loss as a first clinical indicator of seizure activity in temporal lobe epilepsy

Objective: Olfactory dysfunction is well documented in neurological diseases, including temporal lobe epilepsy (TLE), where it may reflect dysfunction of limbic structures integral to both olfaction and seizure generation. While olfactory auras are classically recognized, their predictive utility in the preictal period remains unexplored. This study investigates transient olfactory impairment as a time-sensitive prodromal marker preceding seizure onset in patients with TLE. Methods: Fifteen adults with confirmed or strongly suspected TLE were prospectively enrolled during admission to the Epilepsy Monitoring Unit at King Faisal Specialist Hospital and Research Centre in 2024. Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) at baseline and every 6–8 h until seizure onset. Logistic regression was used to evaluate the association between olfactory dysfunction and time to seizure. Results: Seven of fifteen patients (46.7%) exhibited olfactory impairment prior to seizure onset. These patients experienced significantly shorter intervals between the last test and seizure onset (mean = 1.6 h) compared to those without impairment (mean = 4.1 h, p = 0.0145). Logistic regression revealed a significant inverse association between time and olfactory dysfunction likelihood (OR = 0.33 per hour, 95% CI: 0.09–0.73, p = 0.027), indicating olfactory impairment was more likely closer to seizure onset. Significance: This study is the first to quantitatively link prodromal olfactory dysfunction to seizure onset in TLE, identifying it as a potentially accessible, low-cost, non-invasive biomarker. These findings suggest a novel adjunct for seizure forecasting, and support future development of olfaction-based prediction strategies. Larger scale studies are warranted to validate these results and investigate underlying mechanisms connecting olfactory circuits with ictogenesis.