Bilateral gamma knife radiosurgery in severe essential tremor: a prospective trial.

In patients with medically refractory essential tremor, unilateral Gamma Knife radiosurgery (GKS) of the Ventral Intermedius Thalamic nucleus (VIM) is known to improve contralateral tremor with a good safety. Safety of staged bilateral GKS of the VIM has never been strictly evaluated. Our aim was to determine whether staged bilateral VIM-GKS is safe and effective and would avoid side effects, due to bilaterality of the surgery, while providing improvement of tremor impairment. We conducted a prospective, single-arm, phase 2 trial of second-side GKS of the VIM in 33 patients with severe essential tremor and no relevant speech or balance problems. A comprehensive assessment before surgery, as well as 6 and 12 months post-surgery, included a complete neuropsychological testing, the evaluation of voice, speech, gait, posture, tremor severity, activities of daily living, disease related Quality of Life and MRI. The primary endpoint was safety. All patients completed the study after the one year follow up period (19 male, 14 female, 32 right VIM-GKS and 1 left). A single adverse event was observed (hemi-proprioceptive ataxia and dysarthria due to hyper-response 11 months after VIM-GKS). The mean delay between the first and the second GK was 28.7 months. The postoperative cognitive assessment as well as the evaluation of speech, gait and balance showed no significant worsening. The tremor severity score significantly improved by 58.5%, the disability score by 84.8% and the functional impact score by 68.6%. Four patients failed to respond while for the 29 remaining, the mean improvement of the treated upper limb tremor was 74.4%. Quality of life at 12 months was significantly improved. In selected patients with bilaterally disabling essential tremor and without speech, gait or balance concerns, staged bilateral VIM-GKS can be performed with a good safety profile and leads to a major reduction of the tremor and improvement of the quality of life. If confirmed by larger series and longer follow-up, bilateral staged VIM-GKS could be considered as a good option for selected patients presenting with a severe drug-resistant bilaterally disabling essential tremor.