Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a double-blind 12-month evaluation study

2004 ◽  
Vol 101 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Isabelle M. Germano ◽  
Jean-Michel Gracies ◽  
Donald J. Weisz ◽  
Winona Tse ◽  
William C. Koller ◽  
...  

Object. Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been established as an effective treatment for Parkinson disease (PD). Nevertheless, bilateral surgical procedures can be associated with frequent and severe complications. The aim in the present study was to assess the safety and efficacy of unilateral STN stimulation, and the need for a second procedure. Methods. Twelve patients with PD underwent unilateral DBS of the STN and were followed up for 12 months. Patients were assessed at baseline and at each visit in a double-blind fashion by analyzing the Unified PD Rating Scale (UPDRS), ambulation speed, and home diaries. Levodopa-off/stimulation-on UPDRS motor scores were improved by 26 ± 8% (p < 0.05, mean ± standard deviation [SD]) compared with the baseline levodopa-off score; there was a 50% improvement in contralateral features, a 17% improvement ipsilaterally, and a 36% improvement in axial features. The mean ambulation speed increased by 83 ± 44% (p < 0.01, mean ± SD). The medication-on time with dyskinesias was significantly reduced (p < 0.01) and the daily levodopa dose was reduced by 19 ± 6% (p < 0.05, mean ± SD). There were no clinically significant side effects. Conclusions. Unilateral DBS of the STN is safe and well tolerated, and may provide sufficient benefit so that additional surgery is not required.

2004 ◽  
Vol 101 (2) ◽  
pp. 195-200 ◽  
Author(s):  
Antonella Peppe ◽  
Mariangela Pierantozzi ◽  
Andrea Bassi ◽  
Maria Grazia Altibrandi ◽  
Livia Brusa ◽  
...  

Object. The authors compared the effects of deep brain stimulation (DBS) in the globus pallidus internus (GPi) with those in the subthalamic nucleus (STN) in patients with Parkinson disease (PD) in whom electrodes had been bilaterally implanted in both targets. Methods. Eight of 14 patients with advanced PD in whom electrodes had been implanted bilaterally in both the GPi and STN for DBS were selected on the basis of optimal DBS effects and were studied 2 months postsurgery in offand on-stimulus conditions and after at least 1 month of pharmacological withdrawal. Subcutaneous administration of an apomorphine test dose (0.04 mg/kg) was also performed in both conditions. Compared with the off status, the results showed less reduction in the Unified PD Rating Scale Section III scores during DBS in the GPi (43.1%) than during DBS of the STN (54.5%) or DBS of both the STN and GPi (57.1%). The difference between the effects of DBS in the GPi compared with that in the STN or simultaneous DBS was statistically significant (p < 0.01). In contrast, no statistical difference was found between DBS in the STN and simultaneous DBS in the STN and GPi (p < 0.9). The improvement induced by adding apomorphine administration to DBS was similar in all three stimulus modalities. The abnormal involuntary movements (AIMs) induced by apomorphine were almost abolished by DBS of the GPi, but were not affected by stimulation of the STN. The simultaneous stimulation of STN and GPi produced both antiparkinsonian and anti-AIM effects. Conclusions. The improvement of parkinsonian symptoms during stimulation of the GPi, STN, and both nuclei simultaneously may indicate a similar DBS mechanism for both nuclei in inducing antiparkinsonian effects, although STN is more effective. The antidyskinetic effects produced only by DBS of the GPi, with or without STN, may indicate different mechanisms for the antidyskinetic and antiparkinsonian activity related to DBS of the GPi or an additional mechanism in the GPi. These findings indicate that implantation of double electrodes for DBS should not be proposed as a routine procedure, but could be considered as a possible subsequent choice if electrode implantation for DBS of the STN does not control AIMs.


2004 ◽  
Vol 100 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
Mitsuhiro Ogura ◽  
Naoyuki Nakao ◽  
Ekini Nakai ◽  
Yuji Uematsu ◽  
Toru Itakura

Object. Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. Methods. Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as γ-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. Conclusions. Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.


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.


2004 ◽  
Vol 100 (4) ◽  
pp. 606-610 ◽  
Author(s):  
Taro Nimura ◽  
Tadashi Ando ◽  
Keiichiro Yamaguchi ◽  
Takeshi Nakajima ◽  
Reizo Shirane ◽  
...  

Object. Levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD) mimics acute dystonic reactions induced by antipsychotic agents, possibly mediated by σ-receptors; however, there are few reports in which the relationship between σ-receptors and LID in advanced PD is investigated. The binding potential of cerebellar σ-receptors before and after a pallidal surgery for dyskinesia in patients with advanced PD is assessed. Methods. Six patients with advanced PD (male/female ratio 3:3, age 56.7 ± 9.8 years) underwent stereotactic pallidal surgery (two posteroventral pallidotomy procedures and four deep brain stimulation of the globus pallidus internus, including one bilateral case). Clinical features of patients with PD were assessed using Hoehn and Yahr (H & Y) stages, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Schwab and England Activities of Daily Life Scale (S & E). The LID was evaluated by LID severity score. The binding potential of cerebellar σ-receptors was determined before and after the surgery by 11C-nemonapride positron emission tomoraphy, a specific radioligand for σ-receptors in the cerebellum. All clinical scores, especially the LID severity score, were dramatically improved after the surgery (p < 0.05). Preoperatively, contralateral cerebellar binding potential was significantly elevated (p < 0.01), and it was reduced after the surgery, but it was still higher than that of healthy volunteers (p < 0.05). The ipsilateral cerebellar binding potential remained unchanged after the surgery. The level of binding potential did not correlate with H & Y stage, UPDRS, or S & E score, but a strong positive correlation was seen between the binding potential and the preoperative LID severity score when the patients were receiving medication (r = 0.893, p < 0.05). Conclusions. Cerebellar σ-receptors may potentially involve the genesis of LID in advanced PD.


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.


2001 ◽  
Vol 95 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Yoichi Katayama ◽  
Masahiko Kasai ◽  
Hideki Oshima ◽  
Chikashi Fukaya ◽  
Takamitsu Yamamoto ◽  
...  

Object. A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopaintolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III–V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0–400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500–990 mg/day). Methods. The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. Conclusions. Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.


2002 ◽  
Vol 97 ◽  
pp. 592-599 ◽  
Author(s):  
Marcus F. Keep ◽  
Lois Mastrofrancesco ◽  
Daniel Erdman ◽  
Brent Murphy ◽  
Lynn S. Ashby

✓ The authors present the neuroimaging, treatment planning, and radiosurgical technique for the first reported case of unilateral radiosurgical subthalamotomy, which was performed to control motor symptoms associated with advanced Parkinson disease (PD) in a patient who had undergone previous contralateral radiofrequency (RF) pallidotomy. A 73-year-old woman with end-stage PD had undergone RF pallidotomy of the right globus pallidus with resolution of symptoms. Two years following this procedure, due to the natural progression of her disease, she suffered recurrent motor fluctuations, dyskinesia, and worsening bradykinesia of the right side. Her Parkinson's Disease Disability Rating (PDDR) score was 28. Computerized tomography and magnetic resonance (MR) imaging were used to localize the left subthalamic nucleus (STN). The patient underwent gamma knife radiosurgery—a single shot of 120 Gy was administered using the 4-mm collimator helmet. The patient was evaluated up to 42 months after the procedure. The dyskinesia became minimal. Right-sided motor control improved as did her balance. At 3 months after treatment MR imaging demonstrated the radiosurgical lesion in the left STN. At 3.5 years postradiosurgery, she experienced minimal focal (oral) dyskinesia, no bradykinesia or rigidity, and her PDDR score was 11. Radiosurgery of the STN in this case was safe and effective. The STN is a readily localized anatomical target with neuroimaging. Radiosurgery avoids the risks of open procedures.


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.


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.


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