Impact of biologically effective dose on tremor decrease after stereotactic radiosurgical thalamotomy for essential tremor: a retrospective longitudinal analysis

Abstract

Stereotactic radiosurgery (SRS) is one of the surgical alternatives for drug-resistant essential tremor (ET). Here, we aimed at evaluating whether biologically effective dose (BEDGy2.47) is relevant for tremor improvement after stereotactic radiosurgical thalamotomy in a population of patients treated with one (unplugged) isocenter and a uniform dose of 130 Gy. This is a retrospective longitudinal single center study. Seventy-eight consecutive patients were clinically analyzed. Mean age was 69.1 years (median 71, range 36–88). Mean follow-up period was 14 months (median 12, 3–36). Tremor improvement was assessed at 12 months after SRS using the ET rating assessment scale (TETRAS, continuous outcome) and binary (binary outcome). BED was defined for an alpha/beta of 2.47, based upon previous studies considering such a value for the normal brain. Mean BED was 4573.1 Gy2.47 (median 4612, 4022.1–4944.7). Mean beam-on time was 64.7 min (median 61.4; 46.8–98.5). There was a statically significant correlation between delta (follow-up minus baseline) in TETRAS (total) with BED (p = 0.04; beta coefficient − 0.029) and beam-on time (p = 0.03; beta coefficient 0.57) but also between TETRAS (ADL) with BED (p = 0.02; beta coefficient 0.038) and beam-on time (p = 0.01; beta coefficient 0.71). Fractional polynomial multivariate regression suggested that a BED > 4600 Gy2.47 and a beam-on time > 70 min did not further increase clinical efficacy (binary outcome). Adverse radiation events (ARE) were defined as larger MR signature on 1-year follow-up MRI and were present in 7 out of 78 (8.9%) cases, receiving a mean BED of 4650 Gy2.47 (median 4650, range 4466–4894). They were clinically relevant with transient hemiparesis in 5 (6.4%) patients, all with BED values higher than 4500 Gy2.47. Tremor improvement was correlated with BED Gy2.47 after SRS for drug-resistant ET. An optimal BED value for tremor improvement was 4300–4500 Gy2.47. ARE appeared for a BED of more than 4500 Gy2.47. Such finding should be validated in larger cohorts.

Stereotactic radiosurgery in the treatment of essential tremor – a systematic review

“…Other reported ailment include headaches, depression, minor cognitive deficits, sensory loss, and hemichoreiform movements ( 20 , 25 , 27 , 28 ). Tuleasca et al reported a correlation between BED and the severity of adverse effects ( 32 ). Permanent adverse effects were found in 15 patients including contralateral weakness, numbness, and speech disturbances.…”

“…Tuleasca et al made an assumption that the α/β ratio for normal brain is 2.47 Gy. In their study, it was shown that with BED between 4,300 and 4,500 Gy 2.47 , optimal response rates limiting ARE can be achieved ( 32 ).…”