Elsevier

Autonomic Neuroscience

Volume 234, September 2021, 102835
Autonomic Neuroscience

Vagus nerve ultrasonography in Parkinson's disease: A systematic review and meta-analysis

https://doi.org/10.1016/j.autneu.2021.102835Get rights and content

Abstract

Objectives

Vagus nerve (VN) has been suggested as one of the major routes of Parkinson's disease (PD) progression from enteric nervous system to brain. Therefore, the recent studies have investigated the VN structurally, with a focus on the changes in its size in PD patients using high-frequency ultrasonography. This systematic review and meta-analysis aims to evaluate VN size via ultrasound in PD compared to controls.

Methods

Totally, five studies were included with a total of 238 participants (128 PD patients and 111 controls).

Results

The estimate mean difference in four studies showed that the VN CSA was smaller in PD patients with 0.29 mm2 (95% CI, −0.52 to −0.06) and 0.23 mm2 (95% CI, −0.42 to −0.05) for right and left VNs respectively. The test for overall effect was significant for both measurements (p = 0.01).

Conclusions

This review reveals that there is a degree of vagus nerve atrophy in PD which could be detected sonographically with high confidence, thus can be used as a marker for vagus neuronal lesion or neuropathy. Further studies are needed to examine its clinical correlation thoroughly.

Introduction

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The estimated worldwide incidence ranges from 5 to >35 new cases per 100,000 individuals yearly (Poewe et al., 2017). PD is characterized by progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta along with widespread deposition of the α-synuclein protein. Symptoms comprise motor symptoms including resting tremor, stiffness and bradykinesia (Clarke, 2007; Xu and Pu, 2016). However, up to 66% of dopaminergic neurons are already lost before the onset of motor symptoms (Pakkenberg et al., 1991).

There is cumulative evidence of an enteric origin of neuropathological process leading to PD. Gastrointestinal symptoms are often present in the early phase of PD and result in constipation, gastroparesis or nausea (Klingelhoefer and Reichmann, 2015). Furthermore, vagus nerve (VN) has been suggested as one of the major routes of rostro cranial spread of α-synuclein from the enteric nervous to the dorsal motor nucleus of the vagus (dmX) in the lower brainstem and eventually to SN (Del Tredici and Braak, 2016; Holmqvist et al., 2014). To prove this hypothesis, subdiaphragmatic truncal vagotomy has been associated with a decreased risk for subsequent PD (Liu et al., 2017; Svensson et al., 2015). In addition, studies on animal models confirmed the transport of α-synuclein (derived from human PD brain lysate) from intestine to dmX in a time-dependent manner via the VN (Holmqvist et al., 2014).

In this context, recent studies have investigated the changes in the size of VN in PD patients using high-frequency ultrasonography as a reflection of α-synuclein- induced neuronal loss and as potential non-invasive diagnostic marker for early diagnosis of PD (Fedtke et al., 2018; Pelz et al., 2018; Tsukita et al., 2018; Walter et al., 2018; Laucius et al., 2020). Therefore, the aim of this meta-analysis is to evaluate VN size via ultrasound in PD compared to controls.

Section snippets

Data sources and searches

We searched online databases: Medline (through PubMed), Scopus, Embase and web of science up to September 15, 2020. The search strategy consisted of controlled terms and text words for the concepts of Parkinson's disease, Vagus nerve and Ultrasound. A broad search filter was applied to identify all the studies by using the following search strategy: (vagal OR vagus OR Tenth Cranial Nerve OR CN X OR Nervus Vagus OR Nerve X OR Pneumogastric Nerve) AND (Ultrasonography OR ultrasound OR Ultrasonic

Results

Five studies were included with a total of 238 participants (128 PD patients and 111 controls). Four studies (Fedtke et al., 2018; Pelz et al., 2018; Tsukita et al., 2018; Walter et al., 2018) reported separate values for cross sectional area (CSA) of right and left VN and were included in the meta-analyses for VN CSA. Across the four studies, 198 participants were included (108 PD patients, 91 controls). Laucius et al. (2020) measured average VN diameters in 40 participants (20 PD patients, 20

Discussion

In this meta-analysis, five studies (Fedtke et al., 2018; Pelz et al., 2018; Tsukita et al., 2018; Walter et al., 2018; Laucius et al., 2020) were included with a total of 238 participants (128 PD patients and 111 controls). Four studies (Fedtke et al., 2018; Pelz et al., 2018; Tsukita et al., 2018; Walter et al., 2018) reported separate values for CSA of right and left VN and were included in the meta-analyses for VN-CSA. The fifth study (Laucius et al., 2020) measured average VN's diameters

Conclusions

This systematic review and meta-analysis reveals that there is a degree of vagus nerve atrophy in PD which could be detected sonograpically with high confidence, thus can be used as a marker for vagus neuronal lesion or neuropathy. Further studies are needed to examine its clinical correlation thoroughly.

Declaration of competing interest

The authors have no competing interests to declare.

Acknowledgments

None.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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