Christian Gross, Alain Rougier, Dominique Guehl, Thomas Boraud, Jean Julien, and Bernard Bioulac
✓ The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target.
Seven patients suffering from severe Parkinson's disease (Stages III–V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's Disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.
Emmanuel Cuny, Dominique Guehl, Pierre Burbaud, Christian Gross, Vincent Dousset, and Alain Rougier
Object. The goal of this study was to determine the most suitable procedure(s) to localize the optimal site for high-frequency stimulation of the subthalamic nucleus (STN) for the treatment of advanced Parkinson disease.
Methods. Stereotactic coordinates of the STN were determined in 14 patients by using three different methods: direct identification of the STN on coronal and axial T2-weighted magnetic resonance (MR) images and indirect targeting in which the STN coordinates are referred to the anterior commissure—posterior commissure (AC—PC) line, which, itself, is determined either by using stereotactic ventriculography or reconstruction from three-dimensional (3D) MR images. During the surgical procedure, electrode implantation was guided by single-unit microrecordings on multiple parallel trajectories and by clinical assessment of stimulations. The site where the optimal functional response was obtained was considered to be the best target. Computerized tomography scanning was performed 3 days later and the scans were combined with preoperative 3D MR images to transfer the position of the best target to the same system of stereotactic coordinates. An algorithm was designed to convert individual stereotactic coordinates into an all-purpose PC-referenced system for comparing the respective accuracy of each method of targeting, according to the position of the best target.
Conclusions. The target that is directly identified by MR imaging is more remote (mainly in the lateral axis) from the site of the optimal functional response than targets obtained using other procedures, and the variability of this method in the lateral and superoinferior axes is greater. In contrast, the target defined by 3D MR imaging is closest to the target of optimal functional response and the variability of this method is the least great. Thus, 3D reconstruction adjusted to the AC—PC line is the most accurate technique for STN targeting, whereas direct visualization of the STN on MR images is the least effective. Electrophysiological guidance makes it possible to correct the inherent inaccuracy of the imaging and surgical techniques and is not designed to modify the initial targeting.
Alain Rougier, Dominique Lurton, Bouchaib El Bahh, Véronique Lespinet, Anne-Marie Bidabé, Martine Guillot, and Jean-Marie Caillé
Object. The goal of this study was to determine whether regional cerebral blood flow (rCBF) changes that were found contralaterally to a verified unilateral epileptic focus were associated with the spatiotemporal organization of epileptic abnormalities.
Methods. The CBF in both hippocampi was assessed using stable Xe-enhanced computerized tomography in a series of 19 patients with unilateral mesiotemporal epilepsy. Results were compared according to the distribution of interictal spiking and the spatiotemporal organization of the ictal discharges as determined by stereoelectroencephalography. Two groups were defined: in Group 1 (nine patients), the discharge remained unilateral; in Group 2 (10 patients), the discharge spread to contralateral mesiotemporal structures. For Group 1, the rates of ipsi- and contralateral hippocampal blood flow (HBF) were 32.88 ± 15.53 and 45.88 ± 17.19 ml/100 g/minute, respectively, whereas in Group 2 they were 36.7 ± 11.54 and 36.4 ± 11.27 ml/100 g/minute (mean ± standard deviation). A two-way analysis of variance combining type of seizure (Group 1 compared with Group 2) and HBF (ipsi-compared with contralateral absolute values) demonstrated a main effect for HBF (F[1,17] = 5.051; p = 0.0382), a significant interaction between the two factors (F[1,17] = 6.188; p = 0.0235), and no main effect for type of seizure (F[1,17] = 0.258; p = 0.6178).
Conclusions. In unilateral mesiotemporal epilepsy, asymmetrical interictal hippocampal perfusion was correlated with restricted unilateral ictal discharges, whereas bilateral hippocampal hypoperfusion was correlated with ictal discharges spreading to the contralateral mesiotemporal structures. The lack of correlation between the degree of hypoperfusion and the percentage of neuron cell loss indicated that the decrease in rCBF has both functional and lesional origins.
Bruno Aouizerate, Emmanuel Cuny, Corinne Martin-Guehl, Dominique Guehl, Helene Amieva, Abdelhamid Benazzouz, Colette Fabrigoule, Michele Allard, Alain Rougier, Bernard Bioulac, Jean Tignol, and Pierre Burbaud
✓ Obsessive—compulsive disorder (OCD) is an anxiety disorder associated with recurrent intrusive thoughts and repetitive behaviors. Although conventional pharmacological and/or psychological treatments are well established and effective in treating OCD, symptoms remain unchanged in up to 30% of patients. Deep brain stimulation (DBS) of the anterior limb of the internal capsule has recently been proposed as a possible therapeutic alternative in treatment-resistant OCD. In the present study, the authors tested the hypothesis that DBS of the ventral caudate nucleus might be effective in a patient with intractable severe OCD and concomitant major depression. Psychiatric assessment included the Yale—Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Global Assessment of Functioning (GAF) Scale for determining the symptom severity of OCD, depression, and anxiety as well as the quality of pychosocial and occupational functioning, respectively. Neuropsychological assessment consisted of a wide range of tests primarily exploring memory and executive functions. Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS ≤ 7 and HARS ≤ 10). Remission of OCD (Y-BOCS < 16) was also delayed after 12 or 15 months of DBS. The level of functioning pursuant to the GAF scale progressively increased during the 15-month follow-up period. No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.
Dominique Guehl, Roderick Edwards, Emmanuel Cuny, Pierre Burbaud, Alain Rougier, Julien Modolo, and Anne Beuter
The subthalamic nucleus (STN) is currently recognized as the preferred target for deep brain stimulation (DBS) in patients with Parkinson disease (PD). If there is agreement in the literature that DBS improves motor symptoms significantly, the situation is less clear with respect to the side effects of this procedure. The goal of this study was to correlate the coordinate values of active electrode contacts with the amplitude of residual clinical symptoms and side effects using a mathematical approach.
In this study the investigators examined a cohort of 41 patients with PD who received clinical benefits from DBS after stimulating electrodes had been implanted bilaterally into the STN. The combined scores of residual clinical symptoms plus side effects, including speech disturbance, postural instability, and weight gain, were fitted by using either inverted ellipsoidal exponentials or smooth splines.
These analyses showed evidence of lower combined scores for stimulating contacts at an x coordinate approximately 12.0 to 12.3 mm lateral to the anterior commissure–posterior commissure (AC–PC) line and at a z coordinate approximately 3.1 to 3.3 mm under the AC–PC line. There was insufficient evidence for a preferred y coordinate location.
The authors propose a “best” therapeutic ellipse area that is centered at an x, z location of 12.5 mm, −3.3 mm and characterized by an extension of 1.85 mm in the x direction and 2.22 mm in the z direction. Therapeutic electrode contacts located within this area are well correlated with the lowest occurrence of residual symptoms and the lowest occurrence of side effects independent of STN anatomical considerations. The lack of a significant result in the y direction remains to be explored further.
Bruno Aouizerate, Emmanuel Cuny, Eric Bardinet, Jerome Yelnik, Corinne Martin-Guehl, Jean-Yves Rotge, Alain Rougier, Bernard Bioulac, Jean Tignol, Luc Mallet, Pierre Burbaud, and Dominique Guehl
The ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). However, the respective roles of these structures in the pathophysiology of OCD and MD remain to be clarified. To address this issue, DBS of the ventral striatum was tested in 2 patients with severely distressing and intractable forms of OCD and MD. Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. These findings suggest that the caudate nucleus and nucleus accumbens participate differently in the pathogenesis of both of these psychiatric conditions.