Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic cluster headache. We report the results of a multicentre case series of six patients with chronic cluster headache in whom a DBS in the posterior hypothalamus was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13-35 Hz, n = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under neurostimulation before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders.
Background: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. Objective: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). Methods: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre-and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. Results: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (± 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (± 1.0) lateral, 1.9 mm (± 1.4) posterior, and 1.6 mm (± 2.1) ventral to the midcommissural point. Conclusions: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.
SummaryBackground. The ventro-lateral thalamus is the stereotactic target of choice for severe intention tremor. Nevertheless, the optimal target area has remained controversial, and targeting of the subthalamic area has been suggested to be superior.Patients and methods. Eleven patients with disabling intention tremor of different etiology (essential tremor (n ¼ 8), multiple sclerosis (n ¼ 2) and one with, spinocerebellar ataxia) were implanted bilaterally with DBS electrodes targeted to the ventro-lateral thalamus using micro-recording and micro-stimulation. Among five tracks explored in parallel optimal tracks were chosen for permanent electrode implantation. Postoperative tremor suppression elicited by individual electrode contacts was quantified using a lateralised tremor rating scale at least 3 months (in most patients >1 year) after implantation. The position of electrode contacts was determined retrospectively from stereotactic X-ray exams and by correlation of pre-and postoperative MRI.Results. In all patients, DBS suppressed intention tremor markedly. On average, tremor on the left and right side of the body was improved by 68% (AE19; standard deviation) and 73% (AE21), respectively. In most patients, distal electrode contacts located in the subthalamic area proved to be more effective than proximal contacts in the ventro-lateral thalamus. In stereotactic coordinates, the optimal site was located 12.7 mm (AE1.4; mean AE standard deviation) lateral, 7.0 (AE 1.6) mm posterior, and 1.5 (AE 2.0) mm ventral to the mid-commissural point. In general, the best contacts could be selected for permanent stimulation. Nevertheless, in some instances, more proximal contacts had to be chosen because of adverse effects (paraesthesiae, dysarthria, gait ataxia) which were more pronounced with bilateral stimulation resulting in slightly less tremor suppression on the left and right side of body (63 AE 18 and 68 AE 19%, respectively).Conclusion. Direct comparison of different stimulation sites in individual patients revealed that DBS in the subthalamic area is more effective in suppressing pharmacoresistant intention tremor than the ventro-lateral thalamus proper. Anatomical structures possibly involved in tremor suppression include cerebello-thalamic projections, the prelemniscal radiation, and the zona incerta.
Article abstract-Gait analysis was carried out to assess the effects of L-dopa and bilateral subthalamic nucleus stimulation on gait velocity, cadence, stride length, and gait kinematics in nine patients with PD. Substantial effects of bilateral subthalamic nucleus stimulation on gait, with an increase in gait velocity and stride length comparable to that of a suprathreshold L-dopa dose, were found. Interestingly, stride length was more improved by L-dopa and cadence more by subthalamic nucleus stimulation. In two patients with freezing during the "on" period, subthalamic nucleus stimulation failed to reduce this symptom effectively. The time needed to perform the stand-walk-sit test is also reduced. 1 Bilateral surgery or stimulation of either the internal pallidum (GPi) or the STN is required to improve axial symptoms such as the gait disorder in patients with PD.2,3 A quantitative study investigating the effects of STN stimulation on gait in patients with PD is lacking so far.After several years of treatment, freezing of gait may become resistant to L-dopa. 4 It has not been assessed whether L-dopa-resistant freezing may respond to STN stimulation. Because it has been proposed that preoperative L-dopa response predicts the clinical outcome after STN stimulation, 3 our interest was focused on patients who exhibited a gait disturbance with severe freezing even in their best "on" condition before surgery.Patients and methods. Nine patients with PD (mean age, 56 Ϯ 7 years; Hoehn and Yahr score, III to V) were studied 3 months after bilateral electrode implantation in the STN for deep brain stimulation (DBS). Seven patients had an L-dopa-responsive gait disorder (Group 1) and two patients were identified preoperatively as having severe freezing episodes, even at their best L-dopa response (Group 2). Ten age-matched, healthy subjects served as controls.The UPDRS and gait analysis were carried out following a 12-hour overnight withdrawal of dopaminergic medication. A subscale for gait was constructed (items 13 to 15 of part II and items 29 to 30 of part III of the UPDRS). Gait analysis was carried out under four different conditions: off drug and on stimulation, off drug and off stimulation, on drug and off stimulation, and on drug and on stimulation. For the on-drug condition, a suprathreshold dose of L-dopa was applied. Before gait analysis on a treadmill, the natural walking speed of each patient was measured during overground locomotion in each of the four conditions. Subsequently, a complete gait analysis was carried out on a treadmill, with the speed adjusted exactly to the subjects' individual gait velocities as measured before. Gait was recorded with a three-dimensional infrared movement analysis system, comprising four infrared cameras and video processors (50-Hz sampling rate) connected to a computer. Different gait measurements, including kinematics, were calculated using self-developed software. Results. After surgery, the UPDRS motor score was reduced by 45% with stimulation in the off-drug condition (G...
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