Deep Brain Frameless Radiosurgery for Drug Resistant Invalidating Tremor. Dose Escalation Pilot Study

BACKGROUND The stereotactic lesioning of thalamus and basal ganglia for the treatment of tremor is a well-known procedure which, before the introduction of deep brain stimulation ( DBS), was usually performed using stereotactic surgical procedures.[16] Consistent positive experience in functional radiosurgery using the Gamma Knife or linear accelerators was reported since the first report by Leksell in 1951.[4, 8, 11, 13, 14, 17, 18, 19, 21, 24, 25, 26, 27] CyberKnife (CK), (Accuray Inc., Sunnyvale, California, USA) allows a real frameless stereotactic radiosurgery of recognizable intracranial targets such as arteriovenous malformations (AVMs), tumours, and trigeminal nerve for the treatment of trigeminal neuralgia.[1, 2, 3, 7, 9, 23] When compared to the frame-based radiosurgery , frameless radiosurgery is a pain free procedure which offers the advantage of a better patient's compliance by avoiding local anaesthesia and the discomfort due to wearing the frame for the period of time needed for the whole procedure.

The present literature on functional frame-based radiosurgery (mainly based on Gamma Knife treatments) shows that, while a mean dose of 140 Gy has been effectively used, toxicity increases with higher doses. Moreover the minimal effective dose has never been reported [8, 10, 15, 25 ].

Based on the fact that the 3D dose distribution with Gamma Knife shows some subtle but substantial differences with the Cyberknife, the investigators chose a lower prescription dose compared to the literature data when performing our first attempts to treat movement disorders.

Particularly the prescription dose as the minimum effective dose for a functional disorder such as trigeminal neuralgia was identified.

At that time no previous CyberKnife experiences had been reported. The first two patients treated at our Institution by using these lower treatment doses (75 and 90 Gy respectively) [28] had remarkably positive results thus bringing us to consider the real relative effectiveness of low doses.