Vagus nerve ultrasonography in Parkinson's disease: A systematic review and meta-analysis☆
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.
References (24)
- et al.
Ultrasound of the peripheral nerves in systemic vasculitic neuropathies
J. Neurol. Sci.
(2014) - et al.
Long-term observations in asymmetric immune-mediated neuropathy with vagus hypertrophy using ultrasound of the nerves
J. Neurol. Sci.
(2015, September 15) - et al.
The vagus nerve becomes smaller in patients with Parkinson’s disease: a preliminary cross-sectional study using ultrasonography
Parkinsonism Relat. Disord.
(2018) Verlauf und Nervenfaserarten des Truncus vagalis des Menschen [Topographic anatomy and fiber diameter of the human vagal trunk]
Acta Anat.
(1979)- et al.
Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
J. Neural Transm.
(2003) - et al.
Projections of the dorsal motor nucleus of the vagus to cardiac ganglia of rat atria: an anterograde tracing study
J. Comp. Neurol.
(1999) Parkinson’s disease
Br. Med. J.
(2007)- et al.
Sporadic Parkinson’s disease: development and distribution of α-synuclein pathology
Neuropathol. Appl. Neurobiol.
(2016) - et al.
Ultrasonography of the vagus nerve in Parkinson’s disease
Front. Neurol.
(2018) - et al.
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats
Acta Neuropathol.
(2014)
Pathogenesis of Parkinson disease - the gut-brain axis and environmental factors
Nat. Rev. Neurol.
Ultrasonography of the vagus nerve in the diagnosis of Parkinson’s disease
Parkinsons Dis.
Cited by (10)
Vagus nerve cross-sectional area decreases in Parkinson's disease
2023, Parkinsonism and Related DisordersSonographic vagus nerve atrophy in Parkinson's disease: Myth or fact? A systematic review and meta-analysis of recent evidence answers
2023, Parkinsonism and Related DisordersAssessing the structural and functional changes in vagus nerve in multiple sclerosis
2022, Medical HypothesesCitation Excerpt :It is composed of 80 percent afferent and 20 percent efferent fibers and links the central nervous system with various viscera of the body innervating organs such as heart, lungs, and gastrointestinal (GI) tract [22]. So far the vagus nerve affection has been reported in both patients with central nervous system affection like Parkinson’s disease [23] as well as peripheral nervous system e.g. diabetic polyneuropathy [24] and Guillain-Barré syndrome [25,26]. Our hypothesis proposes that MS can lead to changes in function and structure of VN through affection of the lower brain stem nuclei, resulting in decrease of the output of the parasympathetic system and herewith an imbalance between it and the sympathetic nervous system.
Vagus Nerve Ultrasonography Helps Distinguish Multiple System Atrophy from Other Parkinsonian Syndromes
2023, Movement Disorders Clinical PracticeUltrasound of the normal vagus nerve cross-sectional area in the carotid sheath
2023, Medicine (United States)
- ☆
This paper has not been presented at any meeting before.