BACKGROUND: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 = 8), multiple sclerosis (n = 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% (+/-19; standard deviation) and 73% (+/-21), 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 (+/-1.4; mean +/- standard deviation) lateral, 7.0 (+/-1.6) mm posterior, and 1.5 (+/-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 +/- 18 and 68 +/- 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.

The optimal stimulation site in subthalamic deep brain stimulation (STN‐DBS) was evaluated by correlation of the stereotactic position of the stimulation electrode with the electrophysiologically specified dorsal STN border. In a series of 25 electrodes, best clinical results with least energy consumption were found in contacts located in the dorsolateral border zone, whereas contacts within the subthalamic white matter, e.g., zona incerta, were significantly less effective. We suggest that the dorsolateral STN border should be covered by STN‐DBS. © 2004 Movement Disorder Society

INTRODUCTION: Although deep brain stimulation (DBS) in the ventrolateral thalamus is an effective treatment for severe intention tremor, the optimal site for stimulation is the subject of ongoing debate. METHODS: DBS electrodes were implanted into one of five tracks explored by microrecording and microstimulation in seven patients with essential tremor and six patients with multiple sclerosis. Stereo-tactic coordinates of each electrode contact were determined from stereotactic x-rays, and the efficacy of each contact was assessed. RESULTS: Contacts located ventral to the intercommissural plane reduced lateralized Fahn scores by 63.6 ± 21.1% (right) and 67.9 ± 18.3% (left), whereas dorsal contacts were less effective (20.5 ± 16.4% and 17.6 ± 16.2%, respectively). Similarly, only stimulation below the intercommissural plane resulted in pronounced reduction of intention tremor assessed by magnetic tracking of grasping movements as well as accelerometer total power measuring high-amplitude batwing tremor. The mean coordinates of the most effective contacts (right: 12.9 ± 1.6, −7.4 ± 1.0, −1.6 ± 1.3; left: −12.3 ± 1.2, −7.3 ± 1.7, −2.6 ± 1.1; x, y, z in mm relative to the midcommissural point) suggested stimulation within the subthalamic area, which is corroborated by post hoc correlation with intraoperative microrecordings. Chronaxie values for suppression of tremor (27 ± 14 μs) and induction of ataxia (52 ± 15 μs; P < 0.05) suggested that tremor suppression is caused by modulation of large myelinated fibers. Notably, optimal contacts could not be used for permanent, bilateral stimulation in several instances, because this was associated with side effects, e.g., paresthesias or dysarthria. Whereas the optimal contact was generally chosen for the dominant side (left electrode), contralateral stimulation was performed with less effective contacts located more dorsally. CONCLUSION: For intention tremor, fiber tracks in the subthalamic area (zona incerta, prelemniscal radiation/cerebellothalamic projections, Forel H2) rather than neuronal cell bodies within the ventrolateral thalamus represent an effective target for DBS. Permanent, bilateral stimulation is frequently performed asymmetrically to prevent side effects.

High-frequency deep brain stimulation (DBS) is a powerful instrument for the treatment of neurological movement disorders. Compared to ablative surgery DBS offers a non-lesional modulation of basal ganglia output, its effects are principally reversible, and it is possible to adapt the therapy to the course of the disease and the individual needs of the patient. DBS of the subthalamic nucleus and internal pallidum for advanced Parkinson's disease, of the nucleus ventrointermedius thalami for essential tremor, and of the internal pallidum in severe dystonia have proven a substantial benefit. However, studies evaluating the influence of DBS on the quality of life, carried out for Parkinson's disease and dystonia, are still pending. The treatment of cerebellar tremor in multiple sclerosis (MS) is more complex and careful patient selection is crucial for a functional benefit beyond mere tremor reduction. The available data do not allow an estimate of the long-term efficacy of DBS on MS tremor and studies dealing with this are urgently required.

Background/Aims: The most effective site for subthalamic nucleus (STN) stimulation has remained unclear. The position of active contacts relative to the dorsal margin of the STN was determined. Methods: Electrodes (n = 49) were implanted following STN mapping by microrecording and microstimulation along five tracks (n = 25 patients). The stereotactic position of active contacts was determined and correlated with microrecordings using an algorithm for direct three-dimensional comparisons (n = 37). Results: Most active contacts were detected within ±1.0 mm from the dorsal margin of the STN as defined by microrecording (32.4%) or farther dorsal in the subthalamic area (37.8%), and only 29.7% were localized to the STN proper. This was consistent with the average stereotactic coordinates of the active contacts in these three groups. Conclusion: Our data suggest that the dorsal border area of the STN is the most effective target. Besides the dorsolateral STN (sensorimotor part) this may include projections from/to STN, the zona incerta, and pallidofugal projections in the fields of Forel.

Deep brain stimulation of the subthalamic nucleus (STN–DBS) is an established therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms induced by STN–DBS occurred in a previously psychiatrically healthy patient, focusing on the role of STN–DBS in influencing not only motor but also emotional behaviour. © 2003 Movement Disorder Society

We studied 48 patients after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) who were evaluated 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS) in a standardized levodopa test. Additional follow-up was available in 32 patients after 12 months and in 20 patients after 24 months. At 6 months follow-up, STN-DBS reduced the UPDRS motor score by 50.9% compared to baseline. This improvement remained constant at 12 months with 57.5% and at 24 months with 57.3%. Relevant side effects after STN-DBS included intraoperative subdural hematoma without neurological sequelae (n = 1), minor intracerebral bleeding with slight transient hemiparesis (n = 1), dislocation of impulse generator (n = 2), transient perioperative confusional symptoms (n = 7), psychotic symptoms (n = 2), depression (n = 5), hypomanic behaviour (n = 2), and transient manic psychosis (n = 1). One patient died because of heart failure during the first postoperative year. The current series demonstrates efficacy and safety of STN-DBS beyond the first year after surgical procedure. Complications of STN-DBS comprise a wide range of psychiatric adverse events which, however, were temporary.

Deep-brain stimulation of the subthalamic nucleus appears to reduce levodopa-induced dyskinesias, but whether this effect is caused by the reduction of the total levodopa ingestion or represents a direct effect on the motor system is unknown. Precision grip force of grasping movements and levodopa-induced dyskinesias was analyzed in 10 parkinsonian patients before and after 3 months of deep-brain stimulation of the subthalamic nucleus. Peak grip force was abnormally increased before surgery in the off-drug state and, particularly, in the on-drug state (sensitization). This grip force upregulation normalized with chronic deep-brain stimulation in both conditions (desensitization). Peak-dose dyskinesias also improved, and off-dystonia was completely abolished. Mean dosage of dopaminergic drugs was reduced, but force overflow and dyskinesias were equally improved in 2 patients without a reduction. Despite the same single levodopa test dose, force excess and levodopa-induced dyskinesias were drastically reduced after 3 months of deep-brain stimulation of the subthalamic nucleus. This indicates that direct effects of deep-brain stimulation of the subthalamic nucleus on levodopa-induced dyskinesias are likely to occur. Grip force overflow is a promising parameter to study the desensitizing effect of chronic deep-brain stimulation on levodopa-induced dyskinesias.

Deep brain stimulation (DBS) has developed into an established therapy for the treatment of movement disorders, most commonly Parkinson's disease and tremor of different etiology. The subthalamic nucleus (STN) has evolved as the preferred target for DBS in patients with idiopathic Parkinson's disease. The principal target for DBS in tremor patients is the ventrolateral thalamus which has been explored for ablative procedures (thalamotomy) for some decades. Detailed information about the exact site of chronic stimulation, i.e. the location of the active electrode contacts, are important to map the actual subcortical structures modulating the therapeutic effects of DBS. We compared two different methods not requiring intra-operative teleradiography to determine the stereotactic coordinates of single electrode contacts, (i) correlation of pre- and post-operative MRI, and (ii) post-operative stereotactic skull x-ray. For seven patients implanted bilateral with quadripolar DBS electrodes the coordinates for each contact were determined by both approaches. This revealed for a total of 56 electrode contacts a median euclidean 3D-difference between both methods of 1.18 mm (range 0.42 to 1.93 mm). These data suggest that both approaches may be used to determine the position of single electrode contacts.

Chronic high-frequency stimulation of the subthalamic nucleus has evolved into a routine treatment for motor fluctuations, dyskinesia and medically refractory tremor in Parkinson's disease. The most important predictors for surgical benefit include excellent responsiveness of akinetic-rigid and axial motor symptoms to levodopa, a normal cognitive status and younger age. Current evidence suggests that for patients fulfilling these selection criteria deep brain stimulation of the subthalamic nucleus is superior to standard oral drug therapy in maintaining a good level of health-related quality of life.

With a growing number of patients treated with deep brain stimulation (DBS) operations for both hardware-related complications and routine replacements of impulse generators will be performed more frequently. Failure of DBS systems have to be analyzed thoroughly as this thwarts the enormous efforts required for proper electrode implantation and operative revisions increase the morbidity associated with DBS. A female patient implanted with DBS electrodes for advanced Parkinson's disease presented with straining of the right extension lead and deteriorating gait because of electrode migration. This was due to a malpositioned set screw connector adapting the electrode lead to the extension wire which had been placed below the mastoid process. Following surgical revision with implantation of a new electrode into the STN, electrode dislocation recurred requiring another surgical revision. This was due to renewed connector migration from its parietal position into the cervical region. Straining of extension leads should be recognized as a warning sign for (imminent) electrode dislocation or lead fracture. This may just be the case with connectors located below the mastoid process or in the cervical region, a risk which appears to be increased further with reduced-length extensions. Renewed dislocation of revised extensions may be prevented by securing the position of the connector (e.g. with manipulates).

Summary. The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (±1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (±2.41). The width of the third ventricle correlated with the laterality of the STN (r right =.78; r left =.83) and GP (r right =.76; r left =.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r right =.82; r left =.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.

Wir erleben zur Zeit eine Renaissance der chirurgischen Therapie nicht nur des M. Parkinson, sondern auch anderer Bewegungsstörungen. Die Zielpunkte sind abhängig von den zu behandelnden Symptomen. Die bilaterale Hochfrequenzstimulation des Nucleus subthalamicus wird beim fortgeschrittenen M. Parkinson bevorzugt, und zwar unabhängig davon, ob Fluktuationen, Dyskinesien oder ein Tremor im Vordergrund stehen. Eine wichtige Voraussetzung für das positive Ansprechen auf die STN-Stimulation ist eine gute Dopasensitivität. Die Hauptalternativen der STN-Stimulation beim fortgeschrittenen M. Parkinson oder bei schweren levodopainduzierten Dyskinesien sind die unilaterale Pallidotomie bzw. die uni- oder bilaterale Pallidumstimulation. Thalamotomie und thalamische Stimulation bei tremordominantem M. Parkinson haben nur noch einen geringen Stellenwert. Die wichtigste Operationsindikation neben dem M. Parkinson stellt die generalisierte Dystonie dar. Bei der Dystonie zeichnet sich aktuell ebenso wie beim Hemiballismus und der Hemichorea ein Trend ab, den Globus pallidus internus dem ventrolateral Thalamus gegenüber vorzuziehen. Die gute antidyskinetische Wirkung der Pallidotomie beim M. Parkinson, das geringere Läsionsvolumen und die geringere Inzidenz von Sprechstörungen sind die Hauptargumente für den CPi. Bislang verfügen wir bei der Dystonie im Gegensatz zum M. Parkinson nicht über einen prädiktiven pharmakologischen Test. Die operativen Ergebnisse bei den primären Dystönien erscheinen konstanter als bei der pathophysiologisch uneinheitlicheren sekundären Dystonie. Der essentielle Tremor kann sehr erfolgreich im Nucleus ventrointermedius des Thalamus operiert werden. Gute funktionelle Langzeitergebnisse der thalamischen Chirurgie beim zerebellären Tremor sind wesentlich seltener, die Indikationsstellung bleibt hier eine Einzelfallentscheidung. Die Stimulationstechnik wird der läsionellen Chirurgie aufgrund der geringeren Rate an schwerwiegenden Komplikationen zumeist bevorzugt, unabhängig vom Zielpunkt und der zugrunde liegenden Erkrankung, insbesonders bei bilateralen Eingriffen.