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  • Author or Editor: Philippe Damier x
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Jérôme Yelnik, Philippe Damier, Sophie Demeret, David Gervais, Eric Bardinet, Boulos-Paul Bejjani, Chantal François, Jean-Luc Houeto, Isabelle Arnulf, Didier Dormont, Damien Galanaud, Bernard Pidoux, Philippe Cornu and Yves Agid

Object. The aim of this study was to correlate the clinical improvement in patients with Parkinson disease (PD) treated using deep brain stimulation (DBS) of the subthalamic nucleus (STN) with the precise anatomical localization of stimulating electrodes.

Methods. Localization was determined by superimposing figures from an anatomical atlas with postoperative magnetic resonance (MR) images obtained in each patient. This approach was validated by an analysis of experimental and clinical MR images of the electrode, and the development of a three-dimensional (3D) atlas—MR imaging coregistration method. The PD motor score was assessed through two contacts for each of two electrodes implanted in 10 patients: the “therapeutic contact” and the “distant contact” (that is, the next but one to the therapeutic contact). Seventeen therapeutic contacts were located within or on the border of the STN, most of which were associated with significant improvement of the four PD symptoms tested. Therapeutic contacts located in other structures (zona incerta, lenticular fasciculus, or midbrain reticular formation) were also linked to a significant positive effect. Stimulation applied through distant contacts located in the STN improved symptoms of PD, whereas that delivered through distant contacts in the remaining structures had variable effects ranging from worsening of symptoms to their improvement.

Conclusions. The authors have demonstrated that 3D atlas—MR imaging coregistration is a reliable method for the precise localization of DBS electrodes on postoperative MR images. In addition, they have confirmed that although the STN is the main target during DBS treatment for PD, stimulation of surrounding regions, particularly the zona incerta or the lenticular fasciculus, can also improve symptoms of PD.

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Boulos-Paul Bejjani, Didier Dormont, Bernard Pidoux, Jérôme Yelnik, Philippe Damier, Isabelle Arnulf, Anne-Marie Bonnet, Claude Marsault, Yves Agid, Jacques Philippon and Philippe Cornu

Object. Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance.

Methods. Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure—posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately.

Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted.

Conclusions. At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the “off” and “on” medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopainduced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.

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Sylvie Raoul, Dominique Leduc, Thomas Vegas, Paul Sauleau, Andres M. Lozano, Marc Vérin, Philippe Damier and Youenn Lajat

Object

Deep brain stimulation (DBS) has been shown to be an effective treatment for various types of movement disorders. High-frequency stimulation is applied to specific brain targets through an implanted quadripolar lead connected to a pulse generator. These leads can be used for creating lesions in the brain. The experimental study reported here was designed to examine the electrical parameters that could be used to create reproducible therapeutic lesions in the brain.

Methods

Egg whites were used to measure the relationship between the electrical parameters (current and voltage) applied through the DBS electrode and the size of coagulum. The authors measured current spread from the electrode contact used for lesioning to the adjacent contact. Similar studies were performed in the pallidum or the thalamus of human cadavers. Modeling of the lesion size was performed with simulation of current density and temperature. The ultrastructure of the electrodes after lesioning was verified by electron microscopy.

Results

Coagulation size increased with time but reached a plateau after 30 seconds. For a given set of electrical parameters, reproducibility of the size of lesions was high. Using constant voltage, lesions were larger in egg whites than in cadaveric brains with a mean length of 5 ± 0.6 mm in egg whites at 40 V, 125 mA, impedance 233 Ω; and 4.0 ± 0.8 mm in cadavers at 40 V, 38 mA, impedance 1333 Ω. Computer modeling indicated negligible current flow to the adjacent, unused electrodes. The electrodes showed no structural alterations on scanning electron microscopy after more than 200 lesions.

Conclusions

Results of this study demonstrate that DBS electrodes can be used to generate lesions reproducibly in the brain. The choice of lesioning parameters must take into account differences in impedance between the test medium (egg whites) and the human brain parenchyma.