Gamma knife for functional diseases.

Abstract

Radiosurgery, in the mind of its creator Lars Leksell, was clearly intended to mimic the lesional effects of a surgeon’s knife, hence the name “gamma knife surgery” (GKS) being given to the first completed instrument. The high doses initially selected for the thalamotomies [1], capsulotomies [2], or benign tumors [3, 4] were rapidly identified as being unnecessarily toxic. Since its creation by Leksell in the 1950’s, clinical and experimental radiosurgery experiences have demonstrated that, for classical indications like arteriovenous malformations and benign tumors, radiosurgery is effective owing to its specific histological effects of thrombotic endothelial proliferation and apoptosis, not frank coagulative necrosis. In functional neurosurgery, the strategy is either to target a small volume of normal tissue [i.e., ventrointermediate nucleus (VIM), capsulotomy, trigeminal neuralgia (TN), etc.] with a high dose (maximum 80–140 Gy) or to target a large volume of tissue (i.e., 5–9 cc in epilepsy radiosurgery) with a moderate dose (17–24 Gy at the marginal isodose). Initially, these procedures have been proposed, technically performed, and evaluated based on the hypothesis that their mechanism of action was purely destructive. However, modern neurophysiological, radiological, and histological studies are leading us to question this assumption. Tissue destruction is turning out to be either absent or minimal and in almost all cases insufficient to explain the clinical effects obtained. Therefore, one possibility is that radiosurgery induces changes in the functioning of the neural tissue by inducing remodeling of the glial environment, leading to the modulation of function while preserving basic processing. Thus, the majority of radiosurgery procedures may induce the desired biological effect without requiring a destructive histological effect for the completion of the therapeutic goal. Therefore the concept of “lesional” radiosurgery may be partially incorrect, and a completely hidden world of neuromodulatory effects may remain to be discovered [5, 6].