Nasal septum deviation correlates with asymmetry in Parkinson's disease

BackgroundAsymmetry in motor dysfunction and associated dopaminergic deficit is a common characteristic of Parkinsons disease (PD), yet potential explanations remain mysterious. Hereby, we assessed whether asymmetry in the nasal cavity is related to dopaminergic dysfunction asymmetry in PD patients. MethodsThis cross-sectional, multi-center observational study included 761 PD patients from three cohorts. First, we analyzed data from the Huashan Parkinsonian PET Imaging Database (March 2011 to February 2020), which served as the primary cohort (n=333). Second, we collected de novo data from all PD inpatients in the Hongqiao Campus of Huashan Hospital as internal validation cohort (May 2023 to July 2024, n=77). Finally, we used data from the Parkinsons Progression Markers Initiative as an external validation cohort (n=351). All cohorts included imaging data of structural MRI or CT, as well as dopaminergic neuroimaging using 11C-CFT, 18F-FP-CIT, or 18F-DTBZ on PET or 123I-DaTscan on SPECT. Nasal cavity asymmetry was assessed by visually inspecting the position of nasal septum deviation in structural MRI or CT to determine the dominant side. Both qualitative and quantitative analyses were performed to evaluate the correlations between nasal cavity asymmetry and dopaminergic deficit asymmetry. ResultsIn the primary cohort, 70.2% of patients exhibited consistency between the dominant side of the nasal cavity and the side with a more severe dopaminergic deficit in striatum ({varphi}=0.40, p<0.001). The striatal-specific binding ratios of dopamine uptake were significantly lower on the side ipsilateral to the dominant nasal cavity, and a significantly inverse correlation was found between the asymmetry index of nasal cavity surface area and that of the dopaminergic deficit (r=-0.31, p<0.001). Similar patterns were observed in internal (78.6%, {varphi}=0.57, p<0.001) and external validation cohorts (73.1%, {varphi}=0.45, p<0.001). A stronger correlation was found in sporadic PD ({varphi}=0.67, p<0.001) compared to genetic PD patients ({varphi}=0.31, p=0.3). ConclusionsWe made a novel and robust observation that the nasal cavity asymmetry is correlated with asymmetry in striatal dopaminergic deficiency in PD patients. The finding may have significant implications for both the etiological and clinical research of PD, supporting the nasal pathway as a potential route for both environmental pathogens and PD treatment. Trial Registration Chinese Clinical Trial Registry, ChiCTR2400094198, and https://www.chictr.org.cn/bin/project/edit?pid=251807