Abstracts from the Sixth Bioelectronic Medicine Summit: Neurotechnologies for Individuals and Communities

Introduction: Transcutaneous electrical stimulation of the cymba concha targets the auricular branch of the vagus nerve (taVNS) to activate the cholinergic anti-inflammatory pathway.This non-invasive form of nerve stimulation is an investigational therapy to treat immune mediated inflammatory diseases (IMIDs) with effectiveness reported in short term clinical trials with small sample sizes.Long-term taVNS for this purpose is not well reported.We review a case of successful longterm use in a child with Crohn's disease.Case Report: Patient SS presented at age 4 years old in 2013 with abdominal pain and bloody stools.Crohn's disease involving the duodenum and colon was found.She was treated with mesalamine (2013-2014) unsuccessfully, then azathioprine (2014-2017) leading to a clinical and biochemical remission.Due to patient concerns about long term risk of immunomodulatory medication, azathioprine was discontinued.She returned to clinical care in 2019 with abdominal pain, fecal calprotectin 333 ug/g and colonoscopy finding active Crohn's disease of her duodenum and right colon.She enrolled in a 16-week clinical trial using taVNS.The TENS 7000 stimulation device was used with parameters of a normal pulse wave, 20 Hz frequency, and 300 s pulse width for 5 minutes twice daily.At the end of 16 weeks, her abdominal pain resolved with overall no symptoms reported.Her fecal calprotectin normalized to 59 ug/g.She then continued taVNS as her sole long term Crohn's disease maintenance therapy.In the first year, adherence to the taVNS stimulation varied between zero, once, or twice daily use.After 1 year of taVNS, her symptoms remained resolved, however her calprotectin increased to previous levels 388 ug/g.Repeat endoscopy found mildly active duodenitis and much improved but not resolved macroscopic disease in the right colon compared to colonoscopy before taVNS therapy was initiated.In 2021, given active disease persisting, ustekinumab (Interleukin 12/23 antagonist) was initiated and taVNS use was increased to a consistent 5 minutes twice daily with adherence.Two years later in 2023, with durable clinical remission achieved, reevaluation of her disease activity identified a completely normalized fecal calprotectin 14 ug/g and complete mucosal healing (endoscopic and histologic healing) of her duodenum and colon.She continues this combination of ustekinumab and taVNS with excellent growth, nutritional status, and clinical remission of her Crohn's disease to date.Discussion: Transcutaneous electrical neurostimulation of the auricular cymba concha is being investigated for treatment of intestinal IMIDs such as Crohn's disease and ulcerative colitis.Its excellent safety profile allows taVNS to be considered as a potential monotherapy or in combination with a conventional pharmacological therapy as we report here.A limitation of taVNS as compared to an implanted device is the potential for non-adherence, which can impact therapy success.Its mechanistic effect through vagus nerve mediated anti-inflammatory signaling and potentially other neural circuits requires further investigation.*The subject/proxies described in the abstract gave consent permissions for this case report.