Midcommissural Point Research Articles

NEUROPSYCHOLOGICAL EFFECTS AFTER CHRONIC SUBTHALAMIC STIMULATION AND THE TOPOGRAPHY OF THE NUCLEUS IN PARKINSON'S DISEASE

The neuropsychological effects of chronic subthalamic nucleus (STN)-deep brain stimulation (DBS) as a treatment for Parkinson's disease are variable. Whether these side effects result from the target per se or current diffusion into neighboring structures is uncertain. In this study, the relationship between clinical outcomes and coordinates of active contact are analyzed and compared between patients with and without neuropsychological sequelae. Thirty-eight Parkinsonian patients who underwent bilateral STN-DBS were enrolled in this retrospective cohort study. They were followed for at least 12 months. During the follow-up period, they were divided into two groups for comparison; Group A included patients with neuropsychological side effects and Group B was composed of patients without neuropsychological side effects. The position of the active contact of the electrode was defined with postoperative magnetic resonance imaging scans according to the midcommissural line. Active contact coordinates and clinical outcomes were compared for the two groups. Among the 38 Parkinsonian patients who underwent STN-DBS, eight patients who had neuropsychological side effects were assigned to Group A; the other 30 patients were assigned to Group B. In Groups A and B, the mean follow-up periods were 13.9 and 12.1 months, respectively, the Unified Parkinson's Disease Rating Scale motor score was improved by 53.4 and 45.2% (P = 0.24), respectively, and the levodopa equivalent daily dosage was decreased by 68.4 and 46.4% (P = 0.16), respectively. The mean coordinates of active contact in both Groups A and B were x = 10.1 and 10.5 mm, respectively, y = -2.8 and -3.9 mm, respectively, and z = -6.3 and -6.2 mm, respectively, relative to the midcommissural point. A significant difference was observed on the y axis (P = 0.01). When taking spatial influence into consideration, the neuropsychological effects of chronic STN-DBS were related to a significant anteriorly located active contact within the ventral STN in this preliminary study. This might suggest the existence of topography of STN in patients with Parkinson's disease concerning limbic and associative circuits.

Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor

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. 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. 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). 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.

Chronic stimulation of the posterior hypothalamic region for cluster headache: technique and 1-year results in four patients

Cluster headache (CH) is the most severe of the primary headache disorders. Based on the finding that regional cerebral blood flow is increased in the ipsilateral posterior hypothalamic region during a CH attack, a novel neurosurgical procedure for CH was recently introduced: hypothalamic deep brain stimulation (DBS). Two small case series have been described. Here, the authors report their technical approach, intraoperative physiological observations, and 1-year outcomes after hypothalamic DBS in four patients with medically intractable CHs. Patients underwent unilateral magnetic resonance (MR) imaging-guided stereotactic implantation of a Medtronic DBS (model 3387) lead and Soletra pulse generator system. Intended tip coordinates were 3 mm posterior, 5 mm inferior, and 2 mm lateral to the midcommissural point. Microelectrode recording and intraoperative test stimulation were performed. Lead locations were measured on postoperative MR images. The intensity, frequency, and severity of headaches throughout a 1-week period were tracked in patient diaries immediately prior to surgery and after 1 year of continuous stimulation. At the I-year follow-up examination, DBS had produced a greater than 50% reduction in headache intensity or frequency in two of four cases. Active contacts were located 3 to 6 mm posterior to the mammillothalamic tract. Neurons in the target region showed low-frequency tonic discharge. In two previously published case series, headache relief was obtained in many but not all patients. The results of these open-label studies justify a larger, prospective trial but do not yet justify widespread clinical application of this technique.

Update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain with deep brain stimulation of posterior hypothalamus: results and comments

The objective of this study is to describe the therapeutic effect and the technical and surgical problems of deep brain stimulation (DBS) of the posterior hypothalamus over seven years, for treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain. We report a surgical series of 20 patients that underwent DBS of the posterior hypothalamus. This series includes 16 patients with chronic cluster headache (CH), one patient with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and three patients with atypical facial pain. All patients of this series were resistant to any pharmacological and conservative treatment. The stimulated target was the same in the whole series even though stereotactic coordinates of the target referred to the midcommissural point differ slight in the Y anteroposterior value due to individual anatomical variability. The commissures based reference system was adapted to individual anatomical landmarks of the brainstem adding to the registration a third reference point below the commissural plane. The stimulation parameters of unipolar stimulation were similar in the whole series: 180 Hz, 60 mus, 1-3 V. In the CH series, at five years follow-up the percentage of total number of days free from pain attacks improved from 1%-2% to 71%. Ten patients of this series had a complete and persistent pain-free state at 18 months follow-up and the patient with SUNCT has complete pain relief. In the three patients with atypical facial pain, the neurostimulation procedure was absolutely unsuccessful. DBS of the posterior hypothalamus produced a significant and marked reduction of pain bouts in CH patients and in the SUNCT patient. The attempts to treat atypical facial pain in three patients failed.

Reversible cognitive decline after DBS STN in PD and displacement of electrodes

Cognitive decline may follow deep brain stimulation (DBS) of the subthalamic nucleus (STN).1,2 Changes in cognition between stimulation on and off have also been described.3 We describe a patient with severe decline after STN DBS and postoperative electrode displacement. The patient is a 43-year-old woman diagnosed with Parkinson disease (PD) 8 years prior to DBS STN for severe response fluctuations and dyskinesias. Neuropsychological evaluation was normal (table). She used levodopa/carbidopa slow release 400/100 mg daily. View this table: Table Stimulation characteristics, motor scores, and neuropsychological test results at the evaluation times Surgery was performed using MRI, four-tract microrecordings, and macrostimulation for target localization (12 mm lateral, 2 mm posterior, and 4 mm inferior to the midcommissural point [MCP]). The left electrode (model 3389; Medtronic) was implanted in the central trajectory, with the deepest contact 7 mm below MCP. There was considerable CSF leakage from the burr holes. On the right side, no typical STN activity could be recorded. Because test stimulation along the medial trajectory induced a large reduction in rigidity and bradykinesia, the …

The Role of the Supramammillary Commissure in MR Localization of the Subthalamic Nucleus

Purpose: We have discovered a method for localization of the subthalamic nucleus (STN) utilizing the supramammillary commissure (SMC) as reference point. It is our purpose to present our experience and compare our methods with others. Materials and Methods: Sixteen patients targeted for bilateral DBS for 32 total STN targets were studied by 1 mm MP-RAGE images with coronal T2W images. A modified red nucleus and mustache method was applied. The predicted target points were then confirmed with electronic calipers measuring the differences in methods. Results: Modified red nucleus method using Surgiplan®, and EBAL® and BAGM® electronic brain map atlas matched the target loci of 12 mm, –3 mm, –4 mm on an X-, Y-, and Z-coordinate system with zero at the mid-commissural point. From the coronal view Y is fixed at –3 mm. The mustache method was in error with values of X-axis at 14.25 (± 1.41 SD) (p = 0.69), and of Z-axis at –5.0 (± 1.60 SD) (p = 0.55). Three-fourths had moderate to marked ventricular enlargement of the III, but only 3 had enlargement of the frontal horns. Conclusion: The mustache method erred in the X-axis because the thalamocaudate groove was located lateral to the target point of the STN, and in the Z-axis because of varying thicknesses of the SMC. The top of the SMC is directly lateral from the STN target by 12 mm from the anterior and posterior commissures line. The SMC being a recognizable structure with constant relation to the STN should be the target structure.

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording

Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

Microelectrode recording can be a good adjunct in magnetic resonance image–directed subthalamic nucleus deep brain stimulation for parkinsonism

Background The contribution of MER to improving bilateral STN-DBS is debatable. To resolve the controversy and elucidate the role of MER in DBS, we compared the outcome of bilateral STN-DBS surgery with and without MER in parkinsonian patients. Methods From February 2002 to November 2002, the first 7 of 13 consecutive parkinsonian patients received STN-DBS without MER (group A), and the last 6 received STN-DBS with MER (group B). Pre- and postoperative assessments included scoring of UPDRS with video taping, and MR images. Results The mean Hoehn and Yahr stage was 3.6 in group A and 4.0 in group B. The mean follow-up was 7.4 months for group A and 5.3 months for group B. The mean coordinates of the tip of the permanent electrode relative to the mid–commissural point were x = 8.1 mm, y = 4.3 mm, and z = 5.9 mm for group A and x = 10.6 mm, y = 4.1 mm, and z = 6.9 mm for group B. When levodopa was withdrawn from group A for 12 hours at follow-up, the postoperative UPDRS total score improved by 27.6% ( P = .01) and the motor score by 25.4% ( P = .02); their LEDD decreased by 17.5% ( P = .03). In group B, the postoperative UPDRS total score improved by 49.3% ( P = .00002) and the motor score by 45.2% ( P = .0004); LEDD decreased by 48.5% ( P = .01). Conclusions Although STN-DBS is a promising surgical modality for advanced parkinsonian patients, there is an inevitable learning curve associated with adopting this new procedure. Intraoperative MER is an effective way to ensure correct electrode placement in the STN. With the assistance of intraoperative MER, the outcome of STN-DBS can be improved significantly.

Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were "on" and "off" medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging-determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

Comparison of Three Methods of Targeting the Subthalamic Nucleus for Chronic Stimulation in Parkinson's Disease

The success of subthalamic nucleus (STN) surgery for Parkinson's disease depends on accuracy in target determination. The objective of this study was to determine which of the following techniques was most accurate and precise in identifying the location for stimulation in STN deep brain stimulation surgery that is most clinically effective: direct targeting, indirect targeting using the positions of the anterior and posterior commissures, or a technique using the red nucleus (RN) as an internal fiducial marker. We reviewed 14 patients with Parkinson's disease treated with bilateral STN deep brain stimulation (28 STN targets). Electrode implantation was based on direct and indirect targeting using two-dimensional magnetic resonance imaging with refinement using microelectrode recording. Optimal settings, including the contacts used, were determined during the clinical follow-up. The position of the best contact was defined with postoperative magnetic resonance imaging. This location was compared with the modified direct, indirect, and RN-based targets. The mean distances between the targets and the final position of the optimal contact were calculated. The accuracy and variance of each target were analyzed. The mean position of the best contact was x = 12.12 (standard deviation [SD], 1.45 mm), y = -2.41 (SD, 1.63 mm), and z = -2.39 (SD, 1.49 mm) relative to the midcommissural point. The mean distance between the optimal contact position and the planned target was 3.19 mm (SD, 1.19 mm) using the RN-based method, 3.42 mm (SD, 1.34 mm) using indirect targeting, and 4.66 mm (SD, 1.33 mm) using a modified direct target. The mean distance between the optimal contact and the RN-based target was significantly smaller than the mean distance between the optimal contact and the direct target (post hoc with Tamhane's correction, P < 0.001) but not between the optimal contact and the indirect target. The RN-based target had the smallest variance (F test, P < 0.001), indicating greater precision. The use of the RN as an internal fiducial marker for targeting the optimal region of STN stimulation was reliable and closely approximates the position of the electrode contact that provides the optimal clinical results.

Long-term high-frequency bilateral pallidal stimulation for neuroleptic-induced tardive dystonia

The authors report the results of long-term bilateral high-frequency pallidal stimulation in two patients affected by neuroleptic-induced dystonia. The first patient, a 33-year-old man, experienced a dystonic posture of the trunk, with involvement of the neck and upper and lower limbs after 11 years of treatment with neuroleptic drugs. The second patient, a 30-year-old man, presented with a torsion dystonia, spasmodic torticollis, and involuntary movements of the upper limbs, which appeared after 4 years of neuroleptic treatment. Both of these dystonias worsened even after the neuroleptic treatment had been discontinued, and neither patient responded to clozapine or benzodiazepine therapy. The time lapse between the first appearance of dystonia and surgery was, respectively, 5 and 3 years. In each case bilateral stereotactic implantation of electrodes within the globus pallidus internus (GPI) was performed while the patient was in a state of general anesthesia. The electrodes were placed at the following anterior commissure-posterior commissure line-related coordinates: 20 mm lateral to the midline, 6 mm below the intercommissural plane, and 3 mm anterior to the midcommissural point. Electrical stimulation (130 Hz, 1 V, 90 microsec) was begun on the 1st postoperative day. In both patients, a genetic analysis positively ruled out a mutation in the DYT1 gene, and magnetic resonance imaging yielded normal findings in both cases. Extrapyramidal symptoms and dystonia disappeared almost completely and dramatically in both patients just a few days after high-frequency bilateral pallidal stimulation commenced. Both patients regained autonomy and neuroleptic treatment was reinitiated. The follow-up period for both cases was 1 year. Long-term bilateral high-frequency stimulation of GPI resulted in a dramatic and long-lasting improvement of neuroleptic-induced tardive dystonia.

Correspondence of microelectrode mapping with magnetic resonance imaging for subthalamic nucleus procedures

Background Magnetic resonance imaging (MRI) and microelectrode recording (MER) are commonly used to guide stereotactic procedures on the subthalamic nucleus (STN). Little is known about the correlation between the position of the STN as seen on MRI and that as determined by MER mapping. We compared these in 10 patients with Parkinson's disease. Methods The position of the STN was determined by intraoperative MER findings and stereotactic axial T2 magnetic resonance images with 2-mm slice thickness. Images were reconstructed in a 3-dimensional workstation. The anterior, posterior, medial, lateral, dorsal, and ventral borders of the STN defined with the MRI were measured relative to the midcommissural point. The location of STN activity during MER was reconstructed relative to the midcommissural point for comparison. Results Twenty-nine tracks recorded with microelectrodes provided clear spans of STN-like activity in 18 STN nuclei. The coordinates of MER were, in general, within the borders of the STN defined with the MRI. However, when analyzed individually, some of the tracks had STN-like activity outside the borders of the MRI-defined nucleus (mostly <1 mm). Three tracks had STN-like activity recorded between 2 and 3 mm more anterior than the anterior border of the nucleus defined with the MRI. Conclusions There was a good correlation between MER and the borders of the STN defined in the MRI, except for the anterior-posterior axis, in which MER indicated that the STN extended more anteriorly than as suggested by MRI. This should be taken into account in STN surgery.

Two-year Follow-up of Chronic Stimulation of the Posterior Subthalamic White Matter for Tremor-dominant Parkinson's Disease

To determine the efficacy and safety of unilateral deep brain stimulation on the posterior subthalamic white matter, including the zona incerta (ZI) and the prelemniscal radiation (PRL), for tremor-dominant parkinsonian patients and to determine the exact location of electrodes that were most effective. Eight parkinsonian patients with severe resting tremor underwent unilateral stimulation of the ZI/PRL by use of stereotactic guidance. Electrophysiological targeting was obtained by macrostimulation and by somatosensory evoked potentials recorded directly through a quadripolar deep brain stimulation lead. Postoperative computed tomographic scans and magnetic resonance images were performed to confirm anatomic location of the electrode. Parkinsonian motor disabilities were evaluated by use of the Unified Parkinson's Disease Rating Scale in the medication-off state before surgery and every 6 months after electrode implantations. The mean location of the clinically effective contacts was in the posterior subthalamic white matter, including the ZI and the PRL (mean, 5.6 +/- 1.2 mm posterior to the midcommissural point, 3.2 +/- 1.1 mm inferior to the anterior commissure-posterior commissure line, and 10.5 +/- 1.2 mm lateral to the midline). At 24 months after operation, ZI/PRL stimulation resulted in significant improvement in mean Unified Parkinson's Disease Rating Scale motor score by 44.3%, contralateral tremor by 78.3%, contralateral rigidity by 92.7%, and contralateral akinesia by 65.7% above the "off-stimulation" scores. Handwriting, posture, and gait were also improved. There were no or only mild adverse events. Unilateral ZI/PRL stimulation is a reliable and long-term therapeutic modality and can be considered another surgical target for the treatment of tremor-dominant Parkinson's disease.

Location of the active contact within the subthalamic nucleus (STN) in the treatment of idiopathic Parkinson's disease

Background Chronic electrical stimulation of the subthalamic nucleus (STN) has been shown to be safe and effective in the treatment of medically refractory idiopathic Parkinson's disease. The clinically most relevant location of stimulation within the physiologically defined STN has not been confirmed. We reviewed the locations of active electrical contacts in 33 patients who underwent simultaneous bilateral STN deep brain stimulator (DBS) implantation. Methods The location of the microelectrode-defined dorsal STN border was compared to the location of the center of the active contact(s) employed in achieving optimal clinical results 6 to 18 months postoperatively. Furthermore, the location of this optimal contact was determined with respect to each individual patient's midcommissural point. Bilateral monopolar stimulation was employed in 30 patients using quadripolar DBS electrodes. Results After a minimum follow-up period of 6 months, the motor subscores (UPDRS Part III) in the postoperative on-stimulation/off-medication state were 64 ± 18% (mean ± SD) improved as compared to the preoperative off-medication state ( p < 0.01). Additionally, an improvement of 53 ± 38% was noted when comparing the postoperative on-stimulation/on-medication state to the preoperative on-medication state ( p < 0.01). On average, the center of the optimal contact was 13.3 mm lateral, 0.5 mm posterior, 0.1 mm inferior to the mid-commissural point and was 0.1 ± 2.1 mm dorsal to the physiologically defined dorsal STN border. Conclusions While the achieved clinical results are comparable to those published in the literature, it appears that monopolar electrical stimulation at the anterior dorsolateral border of the STN yields optimal clinical results. Further studies are crucial in determining the precise mechanism of various modes of DBS in an effort to maximize clinical outcome.

786 Targeting of the Subthalamic Area Is Superior to the Ventrolateral Thalamus for Severe Intention Tremor, and Asymmetric Stimulation Can Prevent Side Effects

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.

CLUSTER HEADACHE

Objective: To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug‐resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. Methods: Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long‐term, high‐frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. Results: Since this treatment, all five patients continue to be pain‐free after 2 to 22 months of follow‐up monitoring. Two of the five patients have remained pain‐free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high‐frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. Conclusion: These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug‐resistant chronic CHs. These data point to a central pathogenesis for chronic CHs. Comment.—This study is the big kahuna, the description of the surgical treatment of cluster headache by implantation of a radiostimulator in the “hypothalamic cluster generator” first described by Dr. Peter Goadsby's group (May A, Bahra A, Buchel C, Frackowiak RS, Goadsby PJ. PET and MRA findings in cluster headache and MRA in experimental pain. Neurology. 2000; 55:1328‐1335). This is an exquisite match of pathophysiologic understanding and clinical intervention. The patients operated upon by Dr. Franzini's group were severely impaired with refractory cluster headache. Additional patients have received the procedure in Belgium, and I anxiously await published results. The standard surgical procedure for these patients in the United States has been radiofrequency trigeminogangliorhizolysis, described in great detail by Dr. Ninan Mathew in an abstract (Mathew NT, Hurt W, Kailasam J, Meadors L. Percutaneous radiofrequency trigeminal rhizolysis in intractable chronic cluster headache: 20 years experience, 125 patients [abstract]. Neurology. 2002; 58(suppl 3):A495‐A496). Probably, depending on whether the Belgian physicians reproduce the Italian results, the next step will be to try this procedure in North America, because it may offer greater specificity and higher success rates for our most refractory and desperate patients with cluster headache. SJT

Determining the position and size of the subthalamic nucleus based on magnetic resonance imaging results in patients with advanced Parkinson disease.

The subthalamic nucleus (STN) is a target in surgery for Parkinson disease, but its location according to brain atlases compared with its position on an individual patient's magnetic resonance (MR) images is incompletely understood. In this study both the size and location of the STN based on MR images were compared with those on the Talairach and Tournoux, and Schaltenbrand and Wahren atlases. The position of the STN relative to the midcommissural point was evaluated on 18 T2-weighted MR images (2-mm slices). Of 35 evaluable STNs, the most anterior, posterior, medial, and lateral borders were determined from axial images, dorsal and ventral borders from coronal images. These methods were validated using histological measurements in one case in which a postmortem examination was performed. The mean length of the anterior commissure-posterior commissure was 25.8 mm. Subthalamic nucleus borders derived from MR imaging were highly variable: anterior, 4.1 to -3.7 mm relative to the midcommissural point; posterior, 4.2 to 10 mm behind the midcommissural point; medial, 7.9 to 12.1 mm from the midline; lateral, 12.3 to 15.4 mm from the midline; dorsal, 0.2 to 4.2 mm below the intercommissural plane; and ventral, 5.7 to 9.9 mm below the intercommissural plane. The position of the anterior border on MR images was more posterior, and the medial border more lateral, than its position in the brain atlases. The STN was smaller on MR images compared with its size in atlases in the anteroposterior (mean 5.9 mm), mediolateral (3.7 mm), and dorsoventral (5 mm) dimensions. The size and position of the STN are highly variable, appearing to be smaller and situated more posterior and lateral on MR images than in atlases. Care must be taken in relying on coordinates relative to the commissures for targeting of the STN.

Hypothalamic Deep Brain Stimulation for the Treatment of Chronic Cluster Headaches: A Series Report

The objective of this study was to introduce a new surgical treatment for drug-resistant chronic cluster headaches (CH). Because recent functional studies suggested that a hyperactivity of the posterior hypothalamus might be the primary cause of Cluster Headaches (CH) bouts, we designed a prospective study to explore the therapeutic effectiveness of chronic high-frequency stimulation of this region for the treatment of CH. Nine electrodes were stereotactically implanted in the posterior hypothalamus in eight patients suffering from intractable chronic CH. The stereotactic coordinates of the targeted area were 3mm behind the mid-commissural point, 5mm below the mid-commissural point, and 2mm lateral from the midline. Since initiating this treatment in our center, all of the eight patients have improved. Steroid administration has been progressively withdrawn. All of the patients reported that they were pain-free at 1-26months of follow-up. Three of the eight patients were pain-free without any medication while five of the eight required low doses of methysergide and/or verapamil. No noxious side effects from chronic high-frequency hypothalamic stimulation have been observed nor have we encountered any acute complications from the implant procedure. Tolerance was not observed. We conclude that these preliminary results indicate that hypothalamic stimulation is safe and effective for the treatment of drug-resistant, chronic CH. In addition, these data confirm the "central" pathogenesis for chronic CH.

Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease: Magnetic Resonance Imaging Targeting Using Visible Anatomical Landmarks

Background: The aim of the present study was to validate a magnetic resonance imaging (MRI) visual procedure to target the subthalamic nucleus (STN) based on surrounding anatomical landmarks. Methods: 31 consecutive bilaterally implanted parkinsonian patients were included in this study. After identification of the anterior commissure (AC), posterior commissure (PC) and midcommissural point on a three-dimensional T1-weighted sequence, inversion recovery (IR) T2-weighted coronal slices were performed orthogonal to the AC-PC line. On the slice showing the anterior pole of the red nucleus (RN), the target was placed in the inferolateral portion of the subthalamic zone, limited superiorly by the thalamus, laterally by the internal capsule, inferiorly by the substantia nigra and medially by the midline. The distribution of the targets was analyzed in the AC-PC referential. Results: The mean target coordinates were as follows: anteroposterior (AP) = –2.54 mm (±1.37 mm), lateral (LAT) = 12.03 mm (±0.91 mm) and vertical (VERT) = –6.10 mm (±1.52 mm) for the right side, and AP = –2.65 mm (±1.36 mm), LAT = –11.97 mm (±1.30 mm) and VERT = –5.89 mm (±1.52 mm) for the left side. They projected in the inferior portion of the STN on the Schaltenbrand and Wahren atlas [Stuttgart, Thieme, 1977]. Conclusion: Identification of the anterior pole of the RN and the subthalamic zone on coronal IR T2-weighted MRI performed orthogonal to the AC-PC line provides a precise visual procedure to target the STN.

Variability in Position of the Subthalamic Nucleus Targeted by Magnetic Resonance Imaging and Microelectrode Recordings as Compared to Atlas Co-Ordinates

Background: Traditional methods for localisation of target nuclei for deep brain stimulation (DBS) have used brain atlas co-ordinates for initial targeting. It is now possible to visualise the subthalamic nucleus (STN) on magnetic resonance imaging (MRI) and determine the individual variability of its position. Methods: The present study was performed in patients undergoing STN DBS for Parkinson’s disease. The STN was directly targeted from axially obtained MRI and verified with microelectrode recordings. Postoperatively, the most effective contact was identified for each patient, and its position was calculated. Results: Fifty electrodes were inserted in 25 patients. The target position varied considerably in relation to the mid-commissural point. The mean effective contact position lies just dorsal to the location of the STN in a standard brain atlas. Conclusion: The STN varies in position, and can be accurately targeted from MRI alone.