Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease

2002 ◽  
Vol 97 (5) ◽  
pp. 1167-1172 ◽  
Author(s):  
Aviva Abosch ◽  
William D. Hutchison ◽  
Jean A. Saint-Cyr ◽  
Jonathan O. Dostrovsky ◽  
Andres M. Lozano

Object. The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson disease (PD). Little is known about the neurons within the human STN that modulate movement. The authors' goal was to examine the distribution of movement-related neurons within the STN of humans by using microelectrode recording to identify neuronal receptive fields. Methods. Data were retrospectively collected from microelectrode recordings that had been obtained in 38 patients with PD during surgery for placement of STN deep brain stimulation electrodes. The recordings had been obtained in awake, nonsedated patients. Antiparkinsonian medications were withheld the night before surgery. Neuronal discharges were amplified, filtered, and displayed on an oscilloscope and fed to an audio monitor. The receptive fields were identified by the presence of reproducible, audible changes in the firing rate that were time-locked to the movement of specific joint(s). The median number of electrode tracks per patient was six (range two–nine). The receptive fields were identified in 278 (55%) of 510 STN neurons studied. One hundred one tracks yielded receptive field data. Fourteen percent of 64 cells tested positive for face receptive fields, 32% of 687 cells tested positive for upper-extremity receptive fields, and 21% of 242 cells tested positive for lower-extremity receptive fields. Sixty-eight cells (24%) demonstrated multiple-joint receptive fields. Ninety-three cells (65%) with movement-related receptive fields were located in the dorsal half of the STN, and 96.8% of these were located in the rostral two thirds of the STN. Analysis of receptive field locations from pooled data and along individual electrode tracks failed to reveal a consistent somatotopic organization. Conclusions. Data from this study demonstrate a regional compartmentalization of neurons with movement-related receptive fields within the STN, supporting the existence of specific motor territories within the STN in patients suffering from PD.

2002 ◽  
Vol 96 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Tanya Simuni ◽  
Jurg L. Jaggi ◽  
Heather Mulholland ◽  
Howard I. Hurtig ◽  
Amy Colcher ◽  
...  

Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD. Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods. Conclusions. This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.


2003 ◽  
Vol 99 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Galit Kleiner-Fisman ◽  
David N. Fisman ◽  
Elspeth Sime ◽  
Jean A. Saint-Cyr ◽  
Andres M. Lozano ◽  
...  

Object. The use of deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been associated with a marked initial improvement in individuals with advanced Parkinson disease (PD). Few data are available on the long-term outcomes of this procedure, however, or whether the initial benefits are sustained over time. The authors present the long-term results of a cohort of 25 individuals who underwent bilateral DBS of the STN between 1996 and 2001 and were followed up for 1 year or longer after implantation of the stimulator. Methods. Patients were evaluated at baseline and repeatedly after surgery by using the Unified Parkinson's Disease Rating Scale (UPDRS); the scale was applied to patients during periods in which antiparkinsonian medications were effective and periods when their effects had worn off. Postoperative UPDRS total scores and subscores, dyskinesia scores, and drug dosages were compared with baseline values, and changes in the patients' postoperative scores were evaluated to assess the possibility that the effect of DBS diminished over time. In this cohort the median duration of follow-up review was 24 months (range 12–52 months). The combined (ADL and motor) total UPDRS score during the medication-off period improved after 1 year, decreasing by 42% relative to baseline (95% confidence interval [CI 35–50%], p < 0.001) and the motor score decreased by 48% (95% CI 42–55%, p < 0.001). These gains did diminish over time, although a sustained clinical benefit remained at the time of the last evaluation (41% improvement over baseline, 95% CI 31–50%; p < 0.001). Axial subscores at the time of the last evaluation showed only a trend toward improvement (p = 0.08), in contrast to scores for total tremor (p < 0.001), rigidity (p < 0.001), and bradykinesia (p = 0.003), for which highly significant differences from baseline were still present at the time of the last evaluation. Medication requirements diminished substantially, with total medication doses reduced by 38% (95% CI 27–48%, p < 0.001) at 1 year and 36% (95% CI 25–48%, p < 0.001) at the time of the last evaluation; this decrease may have accounted, at least in part, for the significant decrease of 46.4% (95% CI 20.2–72.5%, p = 0.007) in dyskinesia scores obtained by patients during the medication-on period. No preoperative demographic variable, such as the patient's age at the time of disease onset, age at surgery, sex, duration of disease before surgery, preoperative drug dosage, or preoperative severity of dyskinesia, was predictive of long-term outcome. The only predictor of a better outcome was the patient's preoperative response to levodopa. Conclusions. In this group of patients with advanced PD who underwent bilateral DBS of the STN, sustained improvement in motor function was present a mean of 2 years after the procedure, and sustained reductions in drug requirements were also achieved. Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery.


2004 ◽  
Vol 100 (4) ◽  
pp. 611-618 ◽  
Author(s):  
Pantaleo Romanelli ◽  
Gary Heit ◽  
Bruce C. Hill ◽  
Alli Kraus ◽  
Trevor Hastie ◽  
...  

Object. The subthalamic nucleus (STN) is a key structure for motor control through the basal ganglia. The aim of this study was to show that the STN in patients with Parkinson disease (PD) has a somatotopic organization similar to that in nonhuman primates. Methods. A functional map of the STN was obtained using electrophysiological microrecording during placement of deep brain stimulation (DBS) electrodes in patients with PD. Magnetic resonance imaging was combined with ventriculography and intraoperative x-ray film to assess the position of the electrodes and the STN units, which were activated by limb movements to map the sensorimotor region of the STN. Each activated cell was located relative to the anterior commissure—posterior commissure line. Three-dimensional coordinates of the cells were analyzed statistically to determine whether those cells activated by movements of the arm and leg were segregated spatially. Three hundred seventy-nine microelectrode tracks were created during placement of 71 DBS electrodes in 44 consecutive patients. Somatosensory driving was found in 288 tracks. The authors identified and localized 1213 movement-related cells and recorded responses from 29 orofacial cells, 480 arm-related cells, 558 leg-related cells, and 146 cells responsive to both arm and leg movements. Leg-related cells were localized in medial (p < 0.0001) and ventral (p < 0.0004) positions and tended to be situated anteriorly (p = 0.063) relative to arm-related cells. Conclusions. Evidence of somatotopic organization in the STN in patients with PD supports the current theory of highly segregated loops integrating cortex—basal ganglia connections. These loops are preserved in chronic degenerative diseases such as PD, but may subserve a distorted body map. This finding also supports the relevance of microelectrode mapping in the optimal placement of DBS electrodes along the subthalamic homunculus.


2018 ◽  
Vol 17 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Tatsuya Sasaki ◽  
Ken Kuwahara ◽  
Ittetsu Kin ◽  
Mihoko Okazaki ◽  
Susumu Sasada ◽  
...  

Abstract BACKGROUND Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease. OBJECTIVE To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording. METHODS STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed. RESULTS The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and −0.45 ± 1.5, and −2.5 ± 1.1 and −3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position. CONCLUSION Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.


2003 ◽  
Vol 99 (5) ◽  
pp. 863-871 ◽  
Author(s):  
Emad N. Eskandar ◽  
Alice Flaherty ◽  
G. Rees Cosgrove ◽  
Leslie A. Shinobu ◽  
Fred G. Barker

Object. The surgical treatment of Parkinson disease (PD) has undergone a dramatic shift, from stereotactic ablative procedures toward deep brain stimulaion (DBS). The authors studied this process by investigating practice patterns, mortality and morbidity rates, and hospital charges as reflected in the records of a representative sample of US hospitals between 1996 and 2000. Methods. The authors conducted a retrospective cohort study by using the Nationwide Inpatient Sample database; 1761 operations at 71 hospitals were studied. Projected to the US population, there were 1650 inpatient procedures performed for PD per year (pallidotomies, thalamotomies, and DBS), with no significant change in the annual number of procedures during the study period. The in-hospital mortality rate was 0.2%, discharge other than to home was 8.1%, and the rate of neurological complications was 1.8%, with no significant differences between procedures. In multivariate analyses, hospitals with larger annual caseloads had lower mortality rates (p = 0.002) and better outcomes at hospital discharge (p = 0.007). Placement of deep brain stimulators comprised 0% of operations in 1996 and 88% in 2000. Factors predicting placement of these devices in analyses adjusted for year of surgery included younger age, Caucasian race, private insurance, residence in higher-income areas, hospital teaching status, and smaller annual hospital caseload. In multivariate analysis, total hospital charges were 2.2 times higher for DBS (median $36,000 compared with $12,000, p < 0.001), whereas charges were lower at higher-volume hospitals (p < 0.001). Conclusions. Surgical treatment of PD in the US changed significantly between 1996 and 2000. Larger-volume hospitals had superior short-term outcomes and lower charges. Future studies should address long-term functional end points, cost/benefit comparisons, and inequities in access to care.


2005 ◽  
Vol 103 (6) ◽  
pp. 956-967 ◽  
Author(s):  
Frances Weaver ◽  
Kenneth Follett ◽  
Kwan Hur ◽  
Dolores Ippolito ◽  
Matthew Stern

Object. Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. Methods. This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = −0.02). Conclusions. In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.


2005 ◽  
Vol 103 (2) ◽  
pp. 246-251 ◽  
Author(s):  
Valerie Voon ◽  
Jean Saint-Cyr ◽  
Andres M. Lozano ◽  
Elena Moro ◽  
Yu Yan Poon ◽  
...  

Object. Postoperative psychiatric symptoms have been associated with subthalamic deep brain stimulation (DBS) for Parkinson disease (PD), and preoperative psychiatric vulnerability, the effects of surgery, stimulation, medication changes, and psychosocial adjustment have been proposed as causative factors. The variables involved in whether preoperative psychiatric symptoms improve or worsen following surgery are not yet known. In the present study, preoperative psychiatric symptoms were systematically assessed in patients with PD presenting for routine preoperative psychiatric assessment. Methods. Forty consecutive patients with PD presenting for DBS were interviewed using the Mini International Neuropsychiatric Inventory. Current depressive symptoms were quantified using clinician- and patient-rated depression scales. Seventy-eight percent of patients had at least one lifetime or current Axis I psychiatric diagnosis. The prevalence of depression was 60% (95% confidence interval [CI] 45–85), psychosis 35% (95% CI 25–50), and anxiety 40% (95% CI 25–55). These prevalence rates were comparable to or greater than those in the general population of patients with PD. Twenty-three percent of patients required psychiatric treatment for current symptoms prior to being considered eligible for DBS. Conclusions. As part of the selection process for surgery, members of the study population were chosen for their lack of overt dementia or other active disabling psychiatric symptomatology. The incidence rates of psychiatric disorders, including those diseases occurring in the general population affected with PD, were greater than expected. Data in the present study lead one to question the reliability of patient-rated depression scales as the sole instrument for assessing depression. The authors highlight the need for evidence-based guidelines in the management of these preoperative symptoms as well as the involvement of psychiatric personnel in the assessment and management of these symptoms.


2004 ◽  
Vol 100 (6) ◽  
pp. 1084-1086 ◽  
Author(s):  
Denys Fontaine ◽  
Vianney Mattei ◽  
Michel Borg ◽  
Daniel von Langsdorff ◽  
Marie-Noelle Magnie ◽  
...  

✓ The authors report on a patient with Parkinson disease (PD) and severe obsessive—compulsive disorder (OCD), in whom bilateral stimulation of the subthalamic nucleus (STN) was used to treat both PD and OCD symptoms. This 49-year-old man had displayed symptoms of PD for 13 years. Progressively, his motor disability became severe despite optimal medical treatment. In parallel, he suffered severe OCD for 16 years, with obsessions of accumulation and compulsions of gathering and rubbing that lasted more than 8 hours per day. Bilateral high-frequency STN stimulation was performed to treat motor disability. After surgery (at 1-year follow up), motor and OCD symptoms were dramatically improved. The pre- and postoperative Yale—Brown Obsessive—Compulsive Scale scores were 32 and 1, respectively. No additional antiparkinsonian drugs were administered. This case and other recent reports indicate that OCD symptoms can be improved by deep brain stimulation, a finding that opens new perspectives in the surgical treatment of severe and medically intractable OCD.


2004 ◽  
Vol 100 (3) ◽  
pp. 541-546 ◽  
Author(s):  
Erich O. Richter ◽  
Tasnuva Hoque ◽  
William Halliday ◽  
Andres M. Lozano ◽  
Jean A. Saint-Cyr

Object. 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. Methods. 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. Conclusions. 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.


2003 ◽  
Vol 99 (4) ◽  
pp. 772-774 ◽  
Author(s):  
Jörg Spiegel ◽  
Gerhard Fuss ◽  
Martin Backens ◽  
Wolfgang Reith ◽  
Tim Magnus ◽  
...  

✓ Data from previous studies have shown that magnetic resonance (MR) imaging of the head can be performed safely in patients with deep brain stimulators. The authors report on a 73-year-old patient with bilaterally implanted deep brain electrodes for the treatment of Parkinson disease, who exhibited dystonic and partially ballistic movements of the left leg immediately after an MR imaging session. Such dystonic or ballistic movements had not been previously observed in this patient. In the following months, this focal movement disorder resolved completely. This case demonstrates the possible risks of MR imaging in patients with deep brain stimulators.


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