The Effect of Biological Equivalent Dose on Efficacy of Gamma Knife Thalamotomy in Essential Tremor

 Abstract

Introduction: Essential tremor is one of the most common movement disorders, often requiring a combination of pharmacotherapy and surgical interventions for its management. At the University at Buffalo, we have offered Gamma Knife thalamotomy as an alternative to Deep Brain Stimulation procedures in the elderly population where an open surgical procedure would pose significant risk. We hypothesized that the outcomes of Gamma Knife radiosurgery were directly correlated to the Biological Equivalent Dose (BED) delivered – a function of the prescribed dose of radiation in combination with the biological characteristics of the target, treatment delivery time, and its implications on tissue repair – rather than the numeric physical dose alone. Our secondary objective was to develop a quantitative tool for computerized analysis of patient video recordings to further evaluate the effects of treatment.

Patients and Methods: Forty-three patients underwent Gamma thalamotomy between 2003 and 2023 at the University at Buffalo. Clinical, imaging, and dose parameters were compiled into a database for this analysis. Thirty-eight patients had clinical follow-up ranging from 2 to 61 months. Imaging follow-up was performed with MRI in 20 patients and included Diffusion Tensor Imaging (DTI) in 4 patients. Non-contrast CT was used in follow-up of 3 patients. In addition to traditional statistical tools, specific graphing routines were written, and custom software was designed for conducting video-analysis of patient movement recordings.

Results: Overall clinical response with tremor reduction and was seen in 84% of patients. Median response rate was 90% in patients receiving a BED of at least 4600 Gy2.47 vs. 65% in patients who received less (p<0.004). Complications were observed in 5 patients: apraxia (2), hemiparesis (2), and hemorrhage (1). FLAIR signal changes exceeding 4 mm in diameter on MRI at the thalamotomy site were associated with clinical response. Extensive capsular FLAIR change involving the genu and more anterior parts of the internal capsule and/or FLAIR changes in the cerebral peduncle and insular cortex with or without sylvian fissure deformation were associated with clinical evidence of motor deficits. Expectant and corticosteroid management was used in all patients, and recovery was near complete in all cases in terms of motor function except for the patient with hemorrhage who remained weak on the contralateral side. DTI analysis showed significant reduction in the volume of ipsilateral dentato-rubro-thalamic tract fibers after successful radio-surgical lesioning and was associated with good tremor response. Video analysis of patient recordings revealed that treatment response was associated with reduction in hysteresis of the hand motion curve.

Conclusion: We validated that BED is a more effective predictor of treatment efficacy with a clearly demonstrable response threshold. While the occurrence of side effects corresponded to findings on imaging, the numbers of such cases were too small to evaluate correlations with BED. Tractography changes proved to correlate with response as well, but tractography alone was still not adequate to refine lesion placement. Video analysis software developed for this study will be useful in quantitative data analysis in the future after further validation.