Trans-auricular vagus nerve stimulation (taVNS) is feasible, well-tolerated, and may improve motor function in patients with Parkinson's Disease (PD), new research suggests.
The field of noninvasive brain stimulation in PD is in its infancy, but emerging research shows it is a promising approach for some patients, lead study author Vanessa K. Hinson, MD, PhD, professor of neurology and director of the Movement Disorders Program, Medical University of South Carolina, Charleston, told Medscape Medical News.
"It's a very clever approach for a person who might be poorly tolerant of oral drugs or of invasive surgery, and therefore should be explored further," Hinson said.
The findings were presented at the International Congress of Parkinson's Disease and Movement Disorders (MDS) 2022.
Rating Scale Improvement
Dr Vanessa Hinson
The vagus nerve, a main component of the sympathetic and parasympathetic nervous system, is involved in important neurophysiological functions. The small auricular branch connects to the main nerve, which sends information to structures of the brain important to PD, including the locus coeruleus, substantia nigra, hippocampus, thalamus, and prefrontal cortex.
Hinson's group has shown before that VNS can improve movement in animal models of PD. The stimulations enhanced the neurochemicals noradrenaline and dopamine, and reduced cell loss in parts of the brain that occurs in PD, she reported.
Neuroinflammation and oxidative stress was also reduced in the animals after the intervention, she added.
Since those results were published, "the field has started to explode" in terms of interest in pursuing this intervention clinically — especially because the VN can be stimulated noninvasively at the outer ear, said Hinson.
The current study included 30 participants (100% White) aged 40-79 years and with mild to moderate PD, a Hoehn & Yahr stage 2-3, and a Montreal Cognitive Assessment score of 24 or more.
All were randomly assigned to 10 active or sham stimulations (1 hour each) over the course of 2 weeks. For the active stimulation group, electrodes were attached to the outer ear, connecting to the auricula.
The strength of the electrical current was individualized, Hinson noted. "At the time they can feel the stimulation, which is called the perceptional threshold, you ramp up the current a little bit higher," she said.
She added that patients feel a "tingly" sensation at the ear — and likened it to transcutaneous electrical nerve stimulation (TENS), which is used to stimulate muscles in physical therapy.
In the sham group, electrodes were attached to the ear lobe. These participants felt the same tingling feeling and could not tell that they were not receiving an active stimulation, Hinson reported.
Results showed all patients tolerated the treatment well, she said, adding they did not consider the stimulation painful or unpleasant. As the vagal nerve connects to the heart, researchers also examined the impact of the stimulation on blood pressure and heart rate and found no negative effects.
There was an improvement of three points or more on the Unified Parkinson's Disease Rating System III scale in 8 active group members compared with 4 sham group members. The most improved symptom in responders was bradykinesia, followed by tremor.
Outlier Result?
Interestingly, there were statistically significant group differences in semantic fluency, which entails generating words in a given category such as "fruits" within a certain time period, and in phonemic fluency, such as naming words beginning with the letter "F." In fact, there was a decline in these outcomes in the active group and improvement in the sham group.
This may be because the stimulation affected the prefrontal cortex, a brain structure "overseeing word finding and word generation," said Hinson. "Here, the nerve may be overstimulated and producing positive effects on motion and potentially could have led to diminished cognitive performance."
She stressed, though, that the study was small and this result could be an outlier. "If you stimulate 100 patients, you might not see this effect," she said.
As well, these cognitive effects were transient and "not something they subjectively noticed," said Hinson.
Still, this outcome "tells us we need to know more about stimulation parameters: how strongly to stimulate and for how long," she said.
Hinson noted that future studies will use at-home devices and assess the effects of the stimulation for 6 months. From use of VN stimulation in treatment-resistant depression and epilepsy, "we're learning it usually takes a few months for the maximum benefit to occur," she said.
In addition, for future analyses, patients will be assessed while in a functional magnetic imaging scanner so researchers "can see exactly what brain structures are stimulated [instead of] just going by our hypotheses of what we think is stimulated," Hinson said.
Aside from the temporary impact on semantic and phonemic fluency, there were no group differences on other cognitive tests or subjective measures of cognitive functioning, fatigue, freezing of gait, and sleep quality.
Hinson noted that, overall, this noninvasive intervention might be ideal for older patients with PD. If a clinician has this type of patient, "the last thing you want is to treat them with 10 different drugs that might all interact with one another," she said.
Some older patients may also have neuropsychiatric issues such as depression and anxiety, and so may not tolerate oral drugs well, and are poor candidates for invasive stimulation methods such as deep brain stimulation, she added.
Small But Intriguing
Commenting for Medscape Medical News, Ethan Brown, MD, assistant professor of neurology, Weill Institute of Neurosciences, University of California San Francisco, said this study is small but intriguing.
"It demonstrates the potential efficacy of a completely novel approach to improving symptoms in people with PD," said Brown, who was not involved with the research.
Should trans-auricular stimulation prove effective in future studies, "it could have wide-ranging applicability to patients intolerant of more invasive procedures or with complications from medications," he added.
However, as the investigators "importantly highlighted," this approach does have potential side effects such as the impact on cognitive tests — and this is something future studies should pay attention to, Brown concluded.
The study received funding from the Center on Aging at the Medical University of South Carolina and the Murray Center for Research on Parkinson's Disease & Related Disorders at the Medical University of South Carolina. Hinson and Brown have reported no relevant financial relationships.
International Congress of Parkinson's Disease and Movement Disorders (MDS) 2022: Abstract 727. Presented September 16, 2022.
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