Longitudinal Outcomes of Bilateral and Unilateral Proximal Greater Occipital Nerve Pulsed Radiofrequency in Migraine: A Prospective Randomized Controlled Trial.

Background and Objectives: Greater occipital nerve pulsed radiofrequency (GON-PRF) is an effective neuromodulatory treatment for migraine; however, evidence directly comparing unilateral and bilateral approaches remains limited. This prospective randomized controlled trial compared the clinical efficacy of ultrasound-guided proximal GON-PRF performed unilaterally versus bilaterally at the C2 level in patients with migraine. Materials and Methods: A total of 187 patients were randomized to receive unilateral (n = 91) or bilateral (n = 96) ultrasound-guided proximal GON-PRF without concomitant local anesthetic or corticosteroids. Per-protocol analyses included 78 and 88 participants in the unilateral and bilateral groups, respectively. The primary outcome was the change in monthly headache days (MHD) from baseline to 6 months. Secondary outcomes included Visual Analog Scale (VAS) scores, acute medication days (AMD), Headache Impact Test-6 (HIT-6) scores, Migraine Disability Assessment (MIDAS) grades, and Global Perceived Effect (GPE) scores. Longitudinal outcomes were analyzed using multivariable Generalized Estimating Equations (GEE). Results: Of the 187 randomized participants, 166 completed the 6-month follow-up and were included in the per-protocol analysis. Both groups demonstrated significant improvements in all outcomes throughout follow-up (all p < 0.001). At month 6, the Bilateral Group showed lower MHD values (median [IQR]: 7.0 [6.0] vs. 10.0 [6.0], p = 0.030), a higher ≥50% MHD responder rate (77.3% vs. 55.1%, p = 0.003), and lower AMD values (p = 0.024). Adjusted GEE analyses demonstrated significant treatment effects favoring the Bilateral Group for average VAS (p = 0.047) and HIT-6 (p = 0.004). GPE scores also favored the Bilateral Group at month 6 (p = 0.044). No procedure-related complications occurred. Conclusions: Both unilateral and bilateral ultrasound-guided proximal GON-PRF provided significant clinical improvement in patients with migraine. However, bilateral treatment demonstrated superior longitudinal outcomes, including lower headache frequency, reduced acute medication use, higher ≥50% MHD responder rates, and greater patient-reported improvement. These findings remained consistent after adjustment for baseline covariates.