Prospective study of 10 advanced unilateral tremor-rigid PD patients treated with stereotactic radiofrequency ablation of the caudal zona incerta and Fields of Forel showed very large, sustained UPDRS III improvements over 3 years with minimal transient adverse effects.

Provides clinically relevant evidence that infrathalamic ablation can be a durable, relatively safe alternative to DBS in selected patients or low-resource settings, but offers little mechanistic or biomarker insight for pharmacologic therapeutic discovery.

INTRODUCTION: Advanced Parkinson's disease (PD) with a tremor-rigid phenotype poses therapeutic challenges when pharmacological treatments lose efficacy and deep brain stimulation (DBS) is not an option; particularly in contexts where access to implantable neuromodulation therapies is limited. In this scenario, stereotactic ablation of the caudal zona incerta (cZI) and the Fields of Forel has emerged as a surgical alternative, although long-term evidence remains scarce, especially for combined infrathalamic approaches. METHODS: A prospective study was conducted in 10 patients with advanced unilateral PD and a tremor-rigid phenotype, treated with stereotactic radiofrequency in the cZI and Fields of Forel. Motor function was assessed using the UPDRS III at six time points (baseline, 3, 6, 12, 24, and 36 months), allowing the analysis of both early response and long-term clinical stability. Paired Student's t-tests were applied to compare longitudinal changes in UPDRS III between baseline and follow-up assessments. In addition, effect sizes were calculated using Cohen's d. RESULTS: UPDRS III scores were significantly reduced at all follow-ups (p < 0.001), with mean decreases of -25.8 points at 3 months and -36.3 points at 36 months. Effect sizes were very large (d > 4.0). Tremor improved early and was sustained; rigidity and bradykinesia showed marked reductions during the first year with a slight subsequent upward trend; gait demonstrated continuous progression up to 36 months. No major complications were recorded, and transient adverse effects were minimal, consisting of mild and transient postoperative imbalance in two patients, with rapid clinical recovery and no permanent sequelae. CONCLUSION: Stereotactic ablation of the cZI and Fields of Forel provides robust and sustained clinical benefits at 3 years, with a favourable safety profile. These findings highlight the durability of the motor effect of infrathalamic ablative approaches and position this technique as a viable alternative to DBS in selected patients with advanced PD; underscoring the need for multicentre studies to consolidate its role in contemporary functional surgery.