Noninvasive vagus nerve stimulation in Parkinson’s disease: current status and future prospects

Abstract

Introduction: Parkinson's disease (PD) is a common progressive neurodegenerative disorder with multifactorial etiology. While dopaminergic medication is the standard therapy in PD, it provides limited symptomatic treatment and non-pharmacological interventions are currently being trialed. Areas covered: Recent pathophysiological theories of Parkinson's suggest that aggregated α-synuclein form in the gut and spread to nuclei in the brainstem via autonomic connections. In this paper, we review the novel hypothesis that noninvasive vagus nerve stimulation (nVNS), targeting efferent and afferent vagal projections, is a promising therapeutic tool to improve gait and cognitive control and ameliorate non-motor symptoms in people with Parkinson's. We conducted an unstructured search of the literature for any studies employing nVNS in PD as well as for studies examining the efficacy of nVNS on improving cognitive function and where nVNS has been applied to co-occurring conditions in PD. Expert opinion: Evidence of nVNS as a novel therapeutic to improve gait in PD is preliminary, but early signs indicate the possibility that nVNS may be useful to target dopa-resistant gait characteristics in early PD. The evidence for nVNS as a therapeutic tool is, however, limited and further studies are needed in both brain health and disease.

The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline

“…It establishes a crucial connection between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain, which aids in homeostasis of bodily functions. Vagus nerve stimulation is a promising supportive treatment for refractory depression, posttraumatic stress disorder, and inflammatory bowel disease, inhibits cytokine production, and positively effects beneficial monoaminergic brain signaling in psychiatric conditions, such as mood and anxiety [ 61 , 62 , 63 ], and also for the treatment of traumatically injured brain tissues [ 64 , 65 , 66 , 67 , 68 , 69 ]. Gut bacteria have beneficial effects on mood and anxiety through the bioactive factors they produce, which are transported by the vagus nerve to the brain.…”

Factors Influencing Habitual Physical Activity in Parkinson’s Disease: Considering the Psychosocial State and Wellbeing of People with Parkinson’s and Their Carers

“…This association has been previously found in both the quantity (i.e., habitual physical activity) and quality of gait (e.g., spatio-temporal characteristics) in PD. For example, Loprinzi, et al [ 27 ] reported a favourable association between greater moderate-vigorous physical activity and global cognitive function in PD [ 28 ], while significant evidence has been gathered towards the role of cognition in gait quality, as demonstrated by dual-task gait impairments [ 29 , 30 , 31 , 32 ] and the impact of treatments targeting cholinergic pathways [ 33 ]. Therapeutics for cognitive and motor symptoms may aid the maintenance of HPA; for example, deep brain stimulation treatment for six months led to significant increases in walking bout lengths and variability in PwP [ 34 ].…”

Sleep disorders in Lewy body dementia: Mechanisms, clinical relevance, and unanswered questions

“…However, any invasive intervention must be carefully weighed in LBD, and specific trials in patients with dementia will be needed to facilitate a balanced judgement on the risks and benefits of HGNS in LBD and other dementias. Transcranial magnetic stimulation (TMS) may have potential for the treatment of multiple symptom domains in LBD, including sleep disorders 195,196 . Studies have reported beneficial effects for TMS on RLS 197 and EDS (in a recent small RCT in PDD), 198 while a study 199 showed that TMS can also increase respiratory airflow in OSA, by stimulating submental muscles without inducing wakefulness, suggesting that TMS could be a viable non‐invasive strategy for treating OSA in the future.…”

“…Transcranial magnetic stimulation (TMS) may have potential for the treatment of multiple symptom domains in LBD, including sleep disorders. 195,196 Studies have reported beneficial effects for TMS on RLS 197 and EDS (in a recent small RCT in PDD), 198 while a study 199 showed that TMS can also increase respiratory airflow in OSA, by stimulating submental muscles without inducing wakefulness, suggesting that TMS could be a viable non-invasive strategy for treating OSA in the future. Vagal nerve stimulation (VNS) has been shown to improve EDS in treatment-resistant epilepsy.…”