The Ethical Committee of our institution approved the surgical procedure in all of the patients, taking into account the chronicity and severity of the condition, the related burden to families, and the refractoriness to conservative treatments. The relatives of all of the patients provided their written consent after a detailed explanation of its hypothetical rationale and of the surgical risks was given. The stereotactic implantation was performed with the Leksell frame (Eleckta, Stockholm, Sweden) under general anesthesia in all patients. Preoperative antibiotics were administrated to all patients. A preoperative MRI (brain axial volumetric fast spin echo inversion recovery and T2 images) was used to obtain high-definition images for the precise determination of both anterior and posterior commissures and midbrain structures below the commissural plane, such as the mammillary bodies and the red nucleus. MRIs were fused with 2-mm thick computed tomography (CT) slices that were obtained under stereotactic conditions by the use of an automated technique that is based on a mutual-information algorithm (Frame-link 4.0, Sofamor Danek Steathstation; Medtronic, Minneapolis, Minnesota, USA).

The workstation also provided stereotactic coordinates of the target: 3 mm behind the mid-commissural point, 5 mm below this point, and 2 mm lateral from the midline.

A possible error in this intervention could be attributable to the anatomical individual variability of the angle between the brainstem and the commissural plane. To correct this possible error, we introduced a third anatomical landmark, which allowed final target registration. We called this landmark the “interpeduncular nucleus” or “interpeduncular point,” and it is placed in the apex of the interpeduncular cistern 8 mm below the commissural plane at the level of the maximum diameter of the mammillary bodies [6]. The Y value of the definitive target (anteroposterior coordinate to the mid-commissural point in the classical mid-commissural reference system) was corrected in our patients, and the definitive target coordinate was chosen 2 mm posterior to the interpeduncular point instead of 3 mm posterior to the mid-commissural point. A dedicated program and atlas has been developed and is freely available on the internet to get the proper coordinates of the target (www.​angelofranzini.​com/​BRAIN.​htm).

During the surgical session, all patients received general anesthesia. Target control infusion was used. This method of intravenous infusion of anesthetic drugs has been studied for its ability to achieve targeted blood or effect-site concentration for selected drugs. Maintaining a constant plasma or effect compartment concentration of an intravenous anesthetic requires continuous adjustment of the infusion rate according to the pharmacokinetic properties of the drugs, which can be achieved by commercially available target controlled infusion pumps (in our study, we used Injectomat Agilia, Fresenius Kabi, France).

A rigid cannula was inserted through a 3-mm, coronal, paramedian twist-drill hole and placed up to 10 mm from the target. This cannula was used as both a guide for microrecording and for the placement of the definitive electrode (Quad 3389; Medtronic).

As far as microrecording is concerned, in two patients spontaneous neuronal activity was recorded along four trajectories (two in each patient). Along the trajectories, it was possible to identify several types of firing discharge rates and patterns. Of the several recorded neurons, a total of 14 cells located within the posterior hypothalamus were further analyzed. None showed either activation or inhibition after tactile and pinprick stimulation. The average firing rate for these cells was 13 Hz, although nine cells (64 %) showed a low-frequency discharge at around 5 Hz, and the remaining five cells (36 %) discharged at greater frequencies (26 Hz). Several firing patterns have been noticed: four cells exhibited tonic regular discharge, four cells exhibited tonic irregular discharge, four exhibited a bursting discharge, and two had a sporadic firing. Periodicity was described in five units (four bursting and one regular), but the remaining one randomly fired [3]. Microrecordings within the pHyp were performed within 2 mm of the stereotactic coordinates (specifically, as stated previously, 2 mm lateral to the commissural line, 3 mm posterior to the mid-commissural point, and 5 mm below the commissural line).