PURPOSE: Chronic Headache Disorders (CHDs) are one of the most common sequelae after COVID-19 infection, affecting 20% of patients. The pathomechanism of post-COVID CHDs remains unclear. Recent observations during occipital nerve (ON) decompression surgeries in post-COVID CHD patients suggest that enlarged lymph nodes along the nerve path may be one possible contributing factor to nerve compression. This study aims to evaluate the overlap between patient-reported COVID-19 infection and/or vaccination as a contributing factor in the development or exacerbation of ON. METHODS: This prospective cohort study enrolled 428 consecutive patients screened for headache surgery at two academic institutions between 2021 and 2025. Patients diagnosed with ON were included. Standardized patient surveys collected demographics, perceived relationship between COVID-19 and pain symptoms, precipitating events, and pain characteristics. Intraoperative findings were recorded. RESULTS: Of 113 patients diagnosed with ON, 18 (15.9%) reported COVID-19 as a contributing factor: 6 (5.3%) developed new-onset pain following infection (n=4) or vaccination (n=2), while 12 (10.6%) experienced exacerbation of pre-existing symptoms. Other reported precipitating events included head- or neck trauma (39.8%) and iatrogenic injuries (13.3%), while 32.7% reported no clear precipitating event. Nine COVID-19 related cases (50.0%) underwent nerve decompression surgery. Intraoperative findings included vascular dilation (55.6%), enlarged lymph nodes (55.6%) and trapezius fascia abnormalities (66.7%). At median follow-up of 3.0 months (IQR 3.0-12.0), patients reported median overall pain improvement of 85.0% (IQR 65.0-90.0%, n=7), and 86.0% (IQR 56.5-100%, n=9) at the original operative site. Significant postoperative decreases in pain frequency (p=0.023), duration (p=0.016), and intensity (p=0.035) were observed. Outcomes were comparable in patients with (n=5) or without (n=4) lymph node involvement. CONCLUSION: COVID-19 infection and vaccination represent notable precipitating or exacerbating factors for ON, accounting for approximately 1 in 6 cases in our cohort. The intraoperative findings of lymph node enlargement, vascular proliferation, and fascial abnormalities in these patients support an immune-mediated pathomechanism. Importantly, nerve decompression surgery yielded substantial pain relief, with median improvement exceeding 85%. These findings indicate that ON should be considered in the differential diagnosis of persistent headaches following COVID-19 infection or vaccination. In addition, surgical decompression represents a viable treatment option for appropriately selected patients with refractory symptoms.

Abstract ID: AS28