The Role of Biologically Effective Dose in Clinical Improvement and Hyper-Response After Gamma Knife Radiosurgery for Essential Tremor

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is a minimally invasive alternative for drug-resistant essential tremor (ET). The objective of this study was to evaluate whether biologically effective dose (BED Gy2.47 ) is relevant for tremor arrest after SRS for ET. METHODS: Two hundred sixty-one cases were treated in Marseille University Hospital (CHU Timone) between January 2009 and June 2021. The median age was 71.9 years (39.9-91.5). The treated side was the left ventrointermediate nucleus in 237 cases (90.8%). 130 Gy was prescribed in all cases. The median BED Gy2.47 was 4119.3 (3649-4657.9). RESULTS: The median clinical global impression alleviation was 80 (mean 69.6; 0-100). The median percentage of alleviation of the treated hand was 78.6% (mean 69.9; 7-100). A positive response after treatment was encountered in 213 patients (81.6%). The median magnetic resonance reaction volume was 0.085 cc (0-2.04). Radiological hyper-response was encountered in 28 cases (10.7%), with clinical hyper-response being transient and reversible and from which 4.2% was mild hemiparesis (as worse clinical hyper-response). Fractional polynomial revealed that probability of Clinical Global Impression improvement increased with BED Gy2.47 , for values between 3600 and 4200, whereas tremor of the treated hand improvement was higher with BED Gy2.47 between 3800 and 4400 and positive response as a binary outcome suggested values of BED Gy2.47 more than 3800 and less than 4000 as relevant. Hyper-response probability was higher for BED Gy2.47 between 4000 and 4200. CONCLUSION: BED Gy2.47 between 3800 and 4000 is considered as the optimal interval for better clinical improvement after SRS for drug-resistant ET, without magnetic resonance hyper-reaction and potential complications. Neuromodulation using this BED therapeutic window could potentially increase the efficacy and lower the toxicity of this procedure.