Objective: To test the hypothesis that vagus nerve (VN) atrophy is pronounced in the body-first subtype of Parkinson’s disease (PD) and coincides with pupillary dysfunction.

Background: The VN is discussed to represent a major route of disease progression in the body-first subtype of PD [1]. Little is known about the dynamics of VN degeneration in PD and its relation to changes of rostral brainstem autonomic functions.

Method: The cross-sectional area (CSA) of the mid-cervical VN was measured bilaterally in 54 PD patients (21 women; age 68.7±9.4 y; disease duration, 7.2±6.8 y) and 60 control subjects (25 women; age 66.0±8.7 y) on high-resolution ultrasonography [2]. Non-motor symptoms were assessed using the Non-Motor Symptoms Scale (NMSS), and probable REM sleep behavior disorder (pRBD) was diagnosed with the RBD Symptoms Questionnaire. In 20 de-novo therapy-naïve PD patients and 30 age- and sex-matched controls pupil reaction to light (constriction, re-dilation) was recorded on standardized ultrasonographic dynamic pupillometry.

Results: Mean VN CSA was smaller in PD patients compared to controls (t-test, p=0.005), confirming earlier reports [2-4]. VN CSA (bilateral mean) correlated negatively with PD duration (partial correlation controlled for age, r=-0.31, p=0.028) and NMSS score (Spearman test, r=-0.27, p=0.003). PD patients classified as body-first subtype had smaller VN CSA compared to brain-first PD patients (1.61±0.58 vs 1.95±0.76 cm²; p=0.039). VN CSA (right and left measures) correlated with (ipsilateral each) pupil constriction velocity in de-novo PD patients (r=0.44, p<0.001), as in the combined group of de-novo patients and matched controls (r=0.35, p<0.001). Pupil width at rest was, by trend, smaller in de-novo PD patients compared to controls (3.50±0.85 vs 3.81±0.92 mm, p=0.098) and correlated with pupil dilation velocity (patients only: r=0.72, p<0.001; combined group: r=0.61, p<0.001). Participants with pRBD (11 de-novo PD patients, 2 matched controls) had smaller pupil width at rest than those without pRBD (3.31±0.66 vs 3.82±0.95 mm; p=0.005) and, by trend, lower pupil dilation velocity (0.35±0.10 vs 0.39±0.16 mm/s; p=0.052).

Conclusion: VN atrophy in early motor PD stages coincides with pupillary autonomic dysfunction and appears to be associated with body-first subtype of PD. Sympathetic pupillary dysfunction may precede parasympathetic pupillary dysfunction in body-first PD.

References: [1] Borghammer P, Just MK, Horsager J, Skjærbæk C, Raunio A, Kok EH, Savola S, Murayama S, Saito Y, Myllykangas L, Van Den Berge N. A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease. NPJ Parkinsons Dis 2022;8:166. doi: 10.1038/s41531-022-00436-2
[2] Walter U, Tsiberidou P, Kersten M, Storch A, Löhle M. Atrophy of the Vagus Nerve in Parkinson’s Disease Revealed by High-Resolution Ultrasonography. Front Neurol 2018;9:805. doi: 10.3389/fneur.2018.00805
[3] Abdelnaby R, Elsayed M, Mohamed KA, Dardeer KT, Sonbol YT, ELgenidy A, Barakat MH, Alwerdani MM, Maier A. Vagus nerve ultrasonography in Parkinson’s disease: A systematic review and meta-analysis. Auton Neurosci 2021;234:102835. doi: 10.1016/j.autneu.2021.102835
[4] Huckemann S, Mueller K, Averdunk P, Kühn E, Hilker L, Kools S, Scholz L, Bulut Y, Brünger J, Fiegert S, Grüter T, Fisse AL, Motte J, Yoon MS, Gold R, Schneider-Gold C, Tönges L, Pitarokoili K. Vagal cross-sectional area correlates with parasympathetic dysfunction in Parkinson’s disease. Brain Commun 2023;5:fcad006. doi: 10.1093/braincomms/fcad006

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MDS Abstracts - https://www.mdsabstracts.org/abstract/vagus-nerve-degeneration-in-parkinsons-disease-correlation-with-autonomic-symptoms-and-pupillography/