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‘Very smart’ transatrial VNS for Parkinson’s disease

Transatrial vagus nerve stimulation (taVNS) is feasible, well tolerated, and can improve motor function in patients with Parkinson’s disease (PD), suggests new research.

The field of noninvasive brain stimulation in PD is in its infancy, but emerging research shows it’s a promising approach for some patients, study senior author Vanessa K. Hinson, MD, PhD, professor of neurology and director of the Movement Disorders Program, Medical University of South Carolina, Charleston, said Medscape Medical News.

“This is a very smart approach for a person who may have poor tolerance for oral medications or invasive surgery and therefore needs to 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 major component of the sympathetic and parasympathetic nervous systems, is involved in important neurophysiological functions. The small atrial branch connects to the main nerve, which sends information to brain structures important to PD, including the locus coeruleus, substantia nigra, hippocampus, thalamus, and prefrontal cortex.

Hinson’s group has previously shown that VNS can enhance movement in animal models of PD. The stimulation enhanced the neurochemicals norepinephrine and dopamineand reduced cell loss in parts of the brain that occurs in PD, he reported.

Neuroinflammation and oxidative stress were also reduced in the animals after the intervention, he added.

Since those results were published, “the field has started to explode” in terms of interest in performing this intervention clinically, especially since the VN can be stimulated noninvasively in the outer ear, Hinson said.

The current study included 30 participants (100% white) aged 40 to 79 years and with mild to moderate PD, a Hoehn & Yahr stage 2-3, and a Montreal Cognitive Assessment score of 24 or higher.

All were randomized to 10 active or sham stimulations (1 hour each) over the course of 2 weeks. For the active stimulation group, electrodes were placed in the external ear, connecting them to the atrium.

The strength of the electrical current was individualized, Hinson noted. “At the point when they can feel the stimulation, which is called the perception threshold, you increase the current a little bit more,” she said.

He added that patients feel a “tingling” sensation in the ear, and they liked transcutaneous electrical nerve stimulation (TENS), which is used to stimulate muscles in physical therapy.

In the sham group, electrodes were placed on the earlobe. These participants felt the same tingling sensation and couldn’t tell they weren’t receiving active stimulation, Hinson reported.

The results showed that all patients tolerated the treatment well, he said, adding that they did not find the stimulation painful or unpleasant. As the vagus nerve connects to the heart, the researchers also examined the impact of stimulation on blood pressure and heart rate and found no negative effects.

There was an improvement of 3 points or more on the Unified Parkinson’s Disease Rating System III in 8 members of the active group compared to 4 members of the sham group. The symptom that improved the most in the responders was bradykinesia, followed by tremor.

Atypical result?

Interestingly, there were statistically significant group differences in semantic fluency, which involves generating words in a given category, such as “fruits,” within a given time period, and in phonemic fluency, such as naming words beginning with the letter ” F”. In fact, there was a decrease in these results in the active group and an improvement in the sham group.

This may be because the stimulation affects the prefrontal cortex, a brain structure that “supervises word search and generation,” Hinson said. “Here, the nerve may be overstimulated and produce positive effects on movement and could potentially have led to decreased cognitive performance.”

However, he stressed that the study was small and that this result might be an outlier. “If you stimulate 100 patients, you may not see this effect,” she said.

Also, these cognitive effects were transient and “not something that they subjectively noticed,” Hinson said.

Still, this result “tells us that we need to know more about stimulation parameters: how hard to stimulate and for how long,” he said.

Hinson noted that future studies will use devices in the home and test the effects of stimulation for 6 months. From the use of VN pacing in treatment-resistant patients depression other epilepsy“We’re learning that it usually takes a few months for the maximum benefit to occur,” he said..

Also, for future analyses, patients will be evaluated while in a functional magnetic imaging scanner so researchers “can see exactly which brain structures are being stimulated.” [instead of] simply following our hypotheses of what to think stimulated,” said Hinson.

Aside from the temporal impact on semantic and phonological fluency, there were no differences between groups on other cognitive tests or subjective measures of cognitive functioning, fatigue, gait block, and sleep quality.

Hinson noted that, overall, this noninvasive intervention might be ideal for older patients with PD. If a doctor has this type of patient, “the last thing they want is to treat them with 10 different drugs that could interact with each other,” she said.

Some older patients may also have neuropsychiatric problems such as depression and anxiety, so they may not tolerate oral medications well and may not be candidates for invasive stimulation methods such as deep brain stimulationshe added.

small but intriguing

commenting for Medscape Medical NewsEthan Brown, MD, assistant professor of neurology, Weill Institute for Neurosciences, University of California, San Francisco, said this study is small but intriguing.

“It shows the potential efficacy of an entirely novel approach to improve symptoms in people with PD,” said Brown, who was not involved in the research.

If transatrial pacing proves effective in future studies, “it could have wide applicability in patients who cannot tolerate more invasive procedures or who have drug complications,” he added.

However, as the researchers “importantly highlighted,” this approach has potential side effects, such as impact on cognitive tests, and this is something future studies should pay attention to, Brown concluded..

The study received funding from the Medical University of South Carolina Center on Aging and the Murray Center for Research in Parkinson’s Disease and Related Disorders at the Medical University of South Carolina.. Hinson and Brown have disclosed that they have no relevant financial relationships.

International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2022: Summary 727. Presented on September 16, 2022.

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