January 31, 2022 | This article appeared in the January 2022 issue of BioElectRx Business Report
January 31, 2022 | The 25th annual meeting of the North American Neuromodulation Society, which took place in Orlando FL earlier this month, attracted about 1500 researchers, clinicians, and engineers. Though most of the meeting was devoted to pain therapies and other neurological disorders, a session devoted to applied neuromodulation for vascular, non-vascular, visceral, and COVID conditions attracted a sizable number of attendees.
The session was moderated by Jennifer Hah, an assistant professor at Stanford University and director of the Stanford Pelvic Pain program, and Damian Shin, associate professor in the departments of neuroscience & experimental therapeutics and neurology at Albany Medical College.
Tim Lamer, professor of anesthesiology at the Mayo Clinic, led the session off with an overview of neuromodulation for heart failure and life-threatening arythmias. He noted that pain treatment was what got many researchers involved with this application. He said that typical lead placement for treatment of angina is upper thoracic. “The pathophysiology of heart failure is complex,” Lamer noted, citing a 2019 review published in Lancet.
“When you think about cardiac neuromodulation you have to ask what kind of things can we modulate?” he said. Hallmark features are abnormal sympathetic and vagal tone. “Virtually all heart failure patients have increased sympathetic tone and decreased vagal tone,” he said. “That’s potentially amenable to neuromodulation.”
Lamer noted that people with heart failure not only have cardiac myopathies, but skeletal muscle pathology as well. He raised issues such as whether to use spinal cord stimulation devices or vagus nerve stimulation systems, and what waveforms would be best. “Most of these questions we don’t have answers for yet,” he said.
He mentioned three clinical trials of VNS for heart failure, INOVATE, NECTAR, and ANTHEM [BBR Dec21 p7], and one trial of SCS in the upper thoracic area, the DEFEAT HF trial. All but the ANTHEM trial failed. But he pointed out that some of the failed trials produced improvement in secondary measures. Lamar suggested that blunting the “ergoreflex” that links muscle receptors to vasomotor response in HF patients might be an approach worth investigating, perhaps with lower thoracic SCS.
Peter Staats, CMO at National Spine and Pain Centers, gave a presentation on pandemic after effects and the use of neuromodulation to treat COVID-19. “This group is well suited to handle a lot of complications we’re seeing in patients with long COVID,” he said. Among the persistent complications are attention disorder, fatigue, and headache.
Staats explained the impact of the “cytokine storm” in COVID deaths, highlighting the role that inflammation can play. In the early days of the pandemic, he said, one of the cytokines, IL-6, proved to be highly relevant. If it was elevated greater than 6 you had a 100% chance of death. If it was less than 5, you had a 0% chance of death, Staats explained. But the autonomic nervous system can blunt a hyper-inflammatory state via a cholinergic anti-inflammatory pathway. Activation of the vagus nerve can also cause bronchodilation. The FDA granted emergency use authorization for electroCore’s noninvasive VNS system.
Dalia Elmofty, an associate professor of anesthesiology at the University of Chicago, discussed neuromodulation techniques for the treatment of diabetes and vascular disorders. She noted that 20% of patients with Type 1 diabetes will develop diabetic peripheral neuropathy within 20 years. For patients with Type 2 diabetes, this fraction will grow from 10 to 15% at onset to 50% within 10 years. She pointed out that hyperglycemia will damage small blood vessels, which leads to endothelial damage and deficiency in myelin synthesis
Elmofty discussed first-line treatments for diabetes, which includes gabapentin and serotonin-norepinephrine reuptake inhibitors. She noted that responder rates for these varied between 40% and 60%, whereas six-month responder rates for SCS therapy reached 69% in one study and 56% in another. She explained the mechanism by which SCS is thought to increase vasodilitation. Activation of extracellular signal-related kinase (ERK) and protein kinase B (AKT) leads to stimulation of transient receptor potential vanilloid receptor 1 (TRPV) to release calcitonin-gene-related peptide (CRGP), a potent microvascular vasodilator.
The final presenter in the session was Mayank Gupta, president of Kansas Pain Management and adjunct clinical professor at Kansas City University of Medicine and Biosciences. He spoke about peripheral nerve stimulation for the treatment of overactive bladder.
Gupta explained that first-line treatment for OAB is behavioral therapy, while second-line treatment is pharmaceuticals, and third-line treatment includes tibial nerve stimulation, sacral nerve stimulation, and botox therapy. With posterior tibial nerve stimulation, retrograde signals are sent through the tibial nerve to the sacral nerve, which controls the bladder, sphincter, and pelvic floor muscles. Typically, 12 30-minute sessions are delivered one week apart. He cited a metanalysis that reviewed 17 trials with more than 3,000 drug-refractory participants using PTNS, SNS, or botox therapy. SNS performed best for urinary frequency reduction and urinary incontinence episodes per day. PTNS produced the least risk of urinary tract infection. Botox therapy produced the most amount of complications.
