Transcutaneous auricular vagus nerve stimulation improves dysautonomia in patients with hypermobile Ehlers-Danlos syndrome.

BACKGROUND: Autonomic nervous system dysfunction is highly prevalent in hypermobile Ehlers-Danlos syndrome (hEDS) and contributes substantially to multisystem symptoms and reduced quality of life. Neuroimmune dysregulation and chronic low-grade inflammation are increasingly recognized as key mechanisms underlying these manifestations. Transcutaneous auricular vagus nerve stimulation (taVNS) may restore autonomic balance and engage the cholinergic anti-inflammatory pathway. METHODS: In this prospective, single-center, open-label pilot study, fourteen consecutive female patients with hEDS and disabling dysautonomia (Composite Autonomic Symptom Score-31 [COMPASS-31] > 20) underwent weekly 60-minute taVNS sessions for eight weeks. Autonomic symptoms were assessed weekly using COMPASS-31. Quality of life was evaluated at baseline and week 8 using the 36-Item Short-Form Health Survey (SF-36). RESULTS: taVNS was well tolerated, with no serious adverse events. The mean COMPASS-31 total score decreased significantly from 44.6 ± 12.7 at baseline to 28.3 ± 15.4 at week 8 (- 36.5%, p < 0.001). Significant improvements were observed in orthostatic intolerance, gastrointestinal, vasomotor, and secretomotor domains. The SF-36 total score increased by 27.7% (p = 0.07), with statistically significant improvements in physical functioning, physical role, bodily pain, general health, and vitality. CONCLUSIONS: In this pilot study, taVNS was safe and associated with clinically meaningful improvements in dysautonomia in patients with hEDS. These findings support further randomized controlled studies incorporating objective autonomic and neuroimmune biomarkers.