Movement Disorders Vol. 20, No. 3, 2005, pp. 371–386 © 2004 Movement Disorder Society

Clinical/Scientific Notes glia and frontal lobes. Clinical features of HD range from movement disorders to mood disturbances and cognitive decline. Motor dysfunction first presents as chorea then progresses to dystonia and rigidity. Oculomotor deficits have also been documented in HD, such as slower saccade velocity, increased voluntary saccade latency, and an inability to suppress unwanted saccades to newly appearing stimuli.1– 4 Deep brain stimulation (DBS) produces remarkable improvement in the cardinal motor symptoms of Parkinson’s patients (PD), through stimulation of subthalamic nucleus (STN).5 We report on one of the first HD patients to undergo bilateral globus pallidus internus (GPi) DBS implantation for the treatment of severe and disabling chorea and dystonia. Four months after his DBS surgery, the patient performed a series of saccade tasks (pro, anti, and memory-guided) with stimulation ON and OFF to quantitatively document any differences in oculomotor performance due to pallidal DBS.

Pallidal Deep Brain Stimulation Influences Both Reflexive and Voluntary Saccades in Huntington’s Disease Adrian P. Fawcett, BSc,1 Elena Moro, MD,2 Anthony E. Lang, MD,2 Andres M. Lozano, PhD,3 and William D. Hutchison, PhD1,3* 1

Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 2 Department of Medicine, Division of Neurology, The Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada 3 Department of Surgery, Division of Neurosurgery, The Toronto Western Hospital, Toronto, Ontario, Canada Abstract: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is being evaluated as a potential new therapy for patients with Huntington’s disease (HD). In addition to skeletal movement disorders, HD patients have difficulty initiating voluntary saccades and have difficulty in suppressing rapid saccades toward newly appearing stimuli. We measured several saccade parameters in an HD patient who had marked improvement of clinical symptoms with bilateral GPi DBS to determine whether oculomotor performance improved in parallel with clinical scores. Oculomotor performance was assessed using three testing paradigms: pro-saccades, anti-saccades, and memory-guided saccades. The data from the HD patient was also compared to that of two healthy controls. Pallidal DBS decreased pro-saccade latency, total movement time, and the number of correctly executed trials, as well as increasing saccade gain. Memory–saccade performance was negatively affected with stimulation: saccade gain decreased, latency increased, and the patient’s ability to suppress unwanted saccades decreased with stimulation. Our data demonstrate a task-specific improvement of oculomotor deficits in this HD patient with pallidal DBS, supporting a role of GPi in oculomotor control. © 2004 Movement Disorder Society

Case Report A 42-year-old Caucasian man with genetically confirmed HD with severe chorea, speech, swallowing, balance, and gait impairment and relatively preserved neuropsychological and psychiatric conditions was implanted with bilateral GPi stimulators. The patient gave his free and informed consent to participate in the study, and all procedures were reviewed and approved by the University Health Network Research Ethics Board. At the time of testing, the patient was on 200 mg of amantadine BID, 20 mg of omeprazole QD, 0.5 to 1 mg of clonazepam QHS, 1,250 mg of calcium carbonate and vitamin D QHS, and 12.5 mg of tetrabenazine QID.

Surgical Procedure The surgical procedure for stereotactic microelectrodeguided surgery and GP localization has been described in detail elsewhere.6 After implantation of DBS electrodes, postoperative assessment of stimulating parameters optimized the clinical benefit the patient received from stimulation.

Clinical Response to DBS

Key words: basal ganglia; oculomotor control; eye movements

The clinical outcomes in this patient are reported in detail elsewhere.7 Before surgery, the patient’s Unified Huntington’s Disease Rating Scale (UHDRS) motor score was 86, his dystonia subtotal score was 16, and his chorea subtotal score was 25. At the time of testing, stimulation parameters were right pallidum 3.5 V, 70 Hz, 90-␮sec pulse width, contact 2 negative, case positive; left pallidum 2.0 V, 70 Hz, 60-␮sec pulse width, contact 1 negative, case positive. With DBS ON, the UHDRS motor assessment score was 64, dystonia subtotal was 10, chorea subtotal was 11, and speech, swallowing, and gait showed moderate improvement.

Huntington’s disease (HD) is a progressive autosomal dominant disorder with neurodegeneration affecting the basal gan-

*Correspondence to: Dr. William D. Hutchison, Division of Neurosurgery, The Toronto Western Hospital, 399 Bathurst Street MP11-308, Toronto, Ontario M5T 2S8, Canada. E-mail: [email protected] Received 8 January 2004; Revised 11 February 2004; Accepted 19 February 2004 Published online 3 December 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20356

Eye Movement Recordings Saccade tasks were performed initially with the stimulators on, and repeated 10 minutes after the stimulators were turned

371

372

CLINICAL/SCIENTIFIC NOTES

FIG. 1. An eye position trace of a rightward saccade from an Huntington’s disease (HD) patient, illustrating the parameters used for the analysis of the effects of globus pallidus internus (GPi) deep brain stimulation (DBS) on oculomotor performance. FS, first saccade amplitude; FLS, final saccade amplitude; TMT, total movement time. Note the series of hypometric saccades necessitating the definition of first and final amplitude.

off. This time period was chosen because symptoms were shown previously to have sufficiently returned after 10 minutes and to minimize the patient’s discomfort while off DBS therapy.8 When DBS was off, the patient had increased chorea and dystonia in the limbs, but these symptoms did not interfere with his ability to perform the trials. The subject’s gaze was centered on a flat panel that was placed 0.9 m in front of him. The panel had three light-emitting diodes (LEDs) in a horizontal row: left, middle, and right. The right and left LEDs were at ⫹20 degrees and ⫺20 degrees with respect to the middle target. The subject’s head was manually restrained during the testing protocols, to eliminate coordinated head– eye gaze shifts. A Biometrics Model SGH/V-2 Photoelectric Eye Movement Monitor measured eye position. The resolution of the monitor was 0.25 degree, the accuracy was 1 degree, the maximum drift was 50 mV/hour, and the response time was 16 msec. The patient was required to fixate on each LED at the end of each trial for 2 to 3 seconds for calibration purposes. Signals were digitized at 200 Hz by a Cambridge Electronic Design (CED) 1401 computer interface and saved as computer files for off-line analysis by Spike 2.0 v. 4.04 (CED). Data from two healthy controls were used for comparison.

Testing Paradigms Saccades to targets were assessed using three paradigms: a pro-saccade task, an anti-saccade task, and a memory-guided saccade task. Each paradigm was selected to measure the motor performance of reflexive, externally generated movements (pro-saccades) or volitional, internally cued movements (antiand memory-guided saccades). After a brief 2- to 3-minute training period, the subject was cued to perform 50 saccades, 25 to each side, which were presented in random order. During the pro-saccade task, the subject was required to fixate a central

Movement Disorders, Vol. 20, No. 3, 2005

light for 800 msec then make a saccade toward a target LED at 20 degrees eccentricity, which was randomly generated to the right or left direction. In the anti-saccade task, the subject was required to fixate the central LED for 800 msec and then after a gap period of 200 msec, make a horizontal saccade of the same amplitude, but opposite in direction to a randomly illuminated target LED. In the memory-guided task, the subject was required to fixate the central LED and after 4 seconds a target LED came on for 50 msec. The patient was required to fixate the central LED for a further 7 seconds then make a saccade toward the remembered target position. The memoryguided task incorporated a single eccentricity at 20 degrees and not toward targets with several eccentricities (i.e., 5 degrees, 10 degrees, and 15 degrees) to maximize the number of correct trials within the time constraints of a 2-hour testing period. Future studies may investigate the effects of GPi DBS on memory-guided saccades in more detail.

Data Analysis and Statistical Evaluation The latency, direction, gain, and total movement time for each saccade were calculated off-line (Fig. 1). Latency was defined as the duration of time between the appearance of the saccade-cue and the onset of the first saccadic eye movement. Saccade amplitude was measured by first saccade (FS) gain and final saccade (FLS) gain. Saccade gain was defined to be the eccentricity of the eye after a saccade, divided by its intended eccentricity (20 degrees). FS and FLS gain were defined to be the eccentricity of the eye after the first and final saccades made toward the target, respectively. FLS was expected to have a gain of 1.0. Total movement time (TMT) was defined to be the total time it took the patient to move his eyes from the fixation light to the target light. TMT was calculated by subtracting the time when the subject made his first saccade toward the target

1

4

94 0.10 ⫾ 0.06

96 0.14 ⫾ 0.09

0.96 ⫾ 0.09

1.04 ⫾ 0.07

0.98 ⫾ 0.10

1.01 ⫾ 0.10

0.66‡* ⫾ 0.41 0.80‡* ⫾ 0.47 0.76* ⫾ 0.39 0.92 ⫾ 0.26 1.31 ⫾ 0.23 1.45 ⫾ 0.54 0.26 ⫾ 0.05

0.26 ⫾ 0.16

0.49‡* ⫾ 0.39 0.45‡* ⫾ 0.28 1.26* ⫾ 0.39 0.98 ⫾ 0.39 1.27 ⫾ 0.53 1.40 ⫾ 0.45 0.24 ⫾ 0.08

Anti

Mem

Right Left Right Left Right Left Pro

Eye movement parameters from an HD patient and 2 controls that were collected during pro-saccade (Pro), memory-guided saccade (Mem), and anti-saccade (Anti) tasks. HD parameters were shown to be significantly different by ANOVA (P ⬍ 0.05) with respect to condition and direction, whereas directions were pooled for control data. Significant values (P ⬍ 0.05) are marked with an asterisk. Data that was significant when pooled between right and left sides is marked with double-dagger and asterisk. GPi, globus pallidus internus; DBS, deep brain stimulation; HD, Huntington’s disease; C, control; FS, first saccade; FLS, final saccade; TMT, total movement time.

0 0 42 25 47 75

OFF ON

6 0 63 57 50 43 0

52* 46* 69 88 38 15 1.05* ⫾ 0.19 0.74 ⫾ 0.36 0.47* ⫾ 0.22 0.91 ⫾ 0.18 0.78 ⫾ 0.32 0.78 ⫾ 0.61 1.00 ⫾ 0.10

0.62* ⫾ 0.30 0.72 ⫾ 0.19 0.81* ⫾ 0.33 0.75 ⫾ 0.24 0.69 ⫾ 0.20 0.76 ⫾ 0.07

1.01 ⫾ 0.08

1.12* ⫾ 0.16 1.06 ⫾ 0.22 0.83* ⫾ 0.16 1.04 ⫾ 0.08 1.10 ⫾ 0.24 1.14 ⫾ 0.10

0.89* ⫾ 0.13 1.02 ⫾ 0.08 1.17* ⫾ 0.12 0.97 ⫾ 0.11 1.01 ⫾ 0.21 0.89 ⫾ 0.05

0.08 ⫾ 0.04

100

87* 84* 85 83 17 12 0.75‡* ⫾ 0.50 0.73‡* ⫾ 0.32 0.95 ⫾ 0.52 0.84 ⫾ 0.41 0.55 ⫾ 0.30 0.60 ⫾ 0.71 0.56‡* ⫾ 0.30 0.44‡* ⫾ 0.28 0.93 ⫾ 0.38 0.53 ⫾ 0.23 0.89 ⫾ 0.28 0.38 ⫾ 0.13

OFF ON

% Completed

C OFF

TMT

ON C OFF ON

FLS Gain

C OFF ON

FS Gain

C OFF ON

Latency

C Saccade direction Type of task

TABLE 1. Effects of GPi DBS on eye movement parameters from an HD patient compared to controls

C

% Errors

CLINICAL/SCIENTIFIC NOTES

373

from the time when he finished his last saccade toward the target. The percentage of completed trials was defined to be the ratio of correctly executed trials, in the correct direction and within the correct amount of time, over the number of cued trials. Saccade onset and offset were marked using a velocity criterion. During a trial, if the first saccade was in the wrong direction, for example toward the target in the anti-saccade task, the trial was deemed to be an incorrect saccade. Comparison between sides and condition (DBS ON versus OFF) were made with one-way analysis of variance (ANOVA) using SigmaStat. If the ANOVA showed a significant difference, post hoc comparisons were made using Bonferroni t tests. The ␹2 test with Yates’ correction was used to compare the proportion of errors with stimulators on and off. A P value of less than 0.05 was regarded as significant.

Results GPi DBS had task-specific effects on parameters of eye movements (Table 1 and Figs. 2– 4). GPi DBS was shown to improve pro-saccade latency (Figs. 2A and 3A), gain (Fig. 2B), TMT (Fig. 2C), and the number of correctly executed trials in pro-saccades made to either the right or left (Fig. 2D). Improvement in TMT is also demonstrated by increased average rightward pro-saccade velocity in comparison with two controls (Fig. 3B). Apparent detrimental effects of GP DBS were also found in memory-guided saccades made to the right, demonstrated by increased latency (Fig. 4A), decreased FS and FLS gain (Fig. 4B,C) and an increase in saccade errors (Fig. 4D). The total movement time and the number of correctly completed trials did not change with stimulation. There was no observable effect of GPi DBS on any anti-saccade performance, but this finding was confounded by very low numbers of correctly completed trials. A postoperative magnetic resonance imaging scan confirmed that the DBS electrodes were in GP. Analysis of single unit recordings obtained during the DBS surgery confirmed that the left and right stimulating contacts were found to lie in dorsal and ventral GPi, respectively. An illustration of the location of active DBS contacts is shown in Figure 5, which has been corrected for the location of the optic tract and internal capsule, localized by microstimulation mapping.

Discussion This patient’s oculomotor deficits when OFF stimulation were typical for advanced HD patients: an inability to suppress reflexive saccades to suddenly appearing stimuli, delayed initiation of voluntary saccades, and poor performance of antisaccades.1– 4 It is likely that the observed changes resulted from DBS and were not due to nonspecific effects of inattention or fatigue for the following reasons: (1) performance of rightward pro- and memory-guided saccades each improved and worsened, respectively, with stimulation; (2) correct anti-saccade parameters were not significantly affected by DBS; and (3) both control subjects showed no significant difference in performance between sets of tasks. Active contacts of DBS electrodes were confirmed by intraoperative microelectrode mapping to be located in the dorsal left GPi and in ventral right GPi. These contacts were chosen because they gave the greatest clinical benefit. The effects on

Movement Disorders, Vol. 20, No. 3, 2005

374

CLINICAL/SCIENTIFIC NOTES

FIG. 2. Differences in rightward (R) and leftward (L) pro-saccades parameters, ON versus OFF stimulation. A: Latency (s). B: First saccade gain. C: Total movement time. D: The percentage of correctly executed trials. Asterisks denote statistically significant differences (P ⬍ 0.05).

oculomotor function suggest the left contact influenced memory-guided and pro-saccade performance. The areas of GP that were affected by the left contact but not the right contact were dorsal GPi and possibly ventral GPe. DBS mechanisms are not fully elucidated, but there is evidence that its action is inhibitory because it produces similar clinical benefits to electrolytic lesions.9 –11 Other evidence indicates that neurons are excited by DBS, which might also serve to disrupt transmission of phasic oculomotor signals throughout basal ganglia or to brainstem structures.12 Inhibition of dorsal GPi by DBS may be responsible for the observed changes in saccade amplitude, latency, and frequency of incorrect saccades. The basal ganglia are well known to influence purposeful eye movements through actions of the caudate nucleus (CN), the SNr and the STN, but little is known what role the pallidum may have in oculomotor control.13 Previous lesion studies suggest that the pallidum has a contributing oculomotor influence. Bilateral focal lesions of the lentiform nucleus, affecting the putamen and/or pallidum, were

Movement Disorders, Vol. 20, No. 3, 2005

shown to increase the percentage of errors in saccade sequences and impair saccade accuracy in a memory-guided paradigm.14 Pallidotomy has also been shown to affect fixation15 and to decrease internally guided saccade velocity, but not latency.16 Dorsal GPi is known to receive input from caudate regions implicated in oculomotor function.17 Additionally, there is a striato-pallidal-thalamo-striatal loop, through which GPi sends extensive projections to the centromedian nucleus of the thalamus, which then sends projections back to the striatum and conveys sensorimotor information.18 Disruption of the normal activity in this loop or in the areas of GPi that receive oculomotor information from the caudate may cause the observed deficits in internally generated saccade latency and gain with stimulation, as well as the increase in incorrect saccades, because an inability to suppress unwanted saccades is considered a failure of the volitional saccade system.19 Alternatively, because reflexive saccades are generated by direct cortical action of the frontal eye fields and parietal areas on the superior colliculus

CLINICAL/SCIENTIFIC NOTES

375

FIG. 3. A: Eye position traces to the right (up) and left (down) during a pro-saccade (toward target) trial with stimulation on (right side) or off (left side). Cues for fixation (black) and for saccade targets (gray) are shown as boxes above the traces. Note increased latency, particularly in first three saccades, in the OFF condition. B: Average traces of rightward pro-saccades from two controls C1 (n ⫽ 25) and C2 (n ⫽ 26) and the HD patient when ON (n ⫽ 20) and OFF (n ⫽ 12) DBS. The number of correct trials used in each trace is in brackets. Traces were aligned on saccade initiation (time ⫽ 0) and show mean eye position (solid line) and standard error of the mean (SEM) of eye position (dotted lines). Note the change in average saccade velocity with DBS ON.

(SC),20 and because GPi DBS has been previously shown to activate frontal and parietal areas in PD,21 the improved performance on the pro-saccade task with stimulation may be a result of DBS-mediated restoration of visual and/or oculomotor cortical function. Because GPi sends inhibitory projections to the brainstem,18 it is also possible that DBSmediated improvements are due to disinhibition of brainstem oculomotor neurons. This case study of an HD patient demonstrates that GPi DBS modulates the latency and amplitude of both prosaccades and internally guided saccades, as well as influ-

encing the ability to suppress unwanted saccades. Our results showing pallidal modulation of oculomotor function emphasize the need to include pallidal circuitry in oculomotor models and demonstrate that evaluation of eye movement performance may contribute in the assessment of novel DBS therapy. Acknowledgments: A.P.F is funded by the Vision Science Research Program, W.D.H. is funded by the Parkinson’s Society of Canada. We thank Dr. J.A. Sharpe for the use of his Biometrics monitor, and Dr. P. Broussard for reading an earlier version of the manuscript.

Movement Disorders, Vol. 20, No. 3, 2005

FIG. 4. Differences in rightward (R) and leftward (L) memory-guided saccades parameters, ON versus OFF stimulation. A: Latency (s). B: First saccade gain. C: Final saccade gain. D: The percentage of saccade errors. Asterisks denote statistically significant differences (P ⬍ 0.05).

FIG. 5. The gray rectangles indicate the location of deep brain stimulating electrodes used for chronic therapy and evaluation of saccades in this report. Electrophysiological recording tracks are labeled 1 to 6 in the order in which they were taken. The globus pallidus internus (GPi), globus pallidus externus (GPe), optic tract (OT), internal capsule (IC), visual responses (Vi), and muscular contractions (M) in response to intraoperative stimulation are shown.

Movement Disorders, Vol. 20, No. 3, 2005

CLINICAL/SCIENTIFIC NOTES

377

References 1. Lasker AG, Zee DS. Ocular motor abnormalities in Huntington’s disease. Vision Res 1997;37:3639 –3645. 2. Leigh RJ, Newman SA, Folstein SE, Lasker AG, Jensen BA. Abnormal ocular motor control in Huntington’s disease. Neurology 1983;33:1268 –1275. 3. Lasker AG, Zee DS, Hain TC, Folstein SE, Singer HS. Saccades in Huntington’s disease: slowing and dysmetria. Neurology 1988;38: 427– 431. 4. Lasker AG, Zee DS, Hain TC, Folstein SE, Singer HS. Saccades in Huntington’s disease: initiation defects and distractibility. Neurology 1987;37:364 –370. 5. Moro E, Esselink RJ, Xie J, Hommel M, Benabid AL, Pollak P. The impact on Parkinson’s disease of electrical parameter settings in STN stimulation. Neurology 2002;59:706 –713. 6. Lozano AM, Hutchison WD, Tasker RR, Lang AE, Junn F, Dostrovsky JO. Microelectrode recordings define the ventral posteromedial pallidotomy target. Stereotact Funct Neurosurg 1998; 71:153–163. 7. Moro E, Lang AE, Strafella AP, et al. Bilateral globus pallidus stimulation for Huntington’s disease: role of stimulation frequency in clinical results and in a PET study. Ann Neurol. 2004;56:290 – 294. 8. Lopiano L, Torre E, Benedetti F, et al. Temporal changes in movement time during the switch of the stimulators in Parkinson’s disease patients treated by subthalamic nucleus stimulation. Eur Neurol 2003;50:94 –99. 9. Lozano AM, Dostrovsky J, Chen R, Ashby P. Deep brain stimulation for Parkinson’s disease: disrupting the disruption. Lancet Neurol 2002;1:225–231. 10. Lozano AM, Abosch A. Pallidal stimulation for dystonia. Adv Neurol 2004;94:301–308. 11. Tasker RR, Munz M, Junn FS, et al. Deep brain stimulation and thalamotomy for tremor compared. Acta Neurochir Suppl (Wien) 1997;68:49 –53. 12. Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL. Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 2003;23:1916 –1923. 13. Hikosaka O, Takikawa Y, Kawagoe R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol Rev 2000;80:953–978. 14. Vermersch AI, Muri RM, Rivaud S, et al. Saccade disturbances after bilateral lentiform nucleus lesions in humans. J Neurol Neurosurg Psychiatry 1996;60:179 –184. 15. O’Sullivan JD, Maruff P, Tyler P, Peppard RF, McNeill P, Currie J. Unilateral pallidotomy for Parkinson’s disease disrupts ocular fixation. J Clin Neurosci 2003;10:181–185. 16. Blekher T, Siemers E, Abel LA, Yee RD. Eye movements in Parkinson’s disease: before and after pallidotomy. Invest Ophthalmol Vis Sci 2000;41:2177–2183. 17. Alexander GE, Crutcher MD, DeLong MR. Basal gangliathalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res 1990;85:119 – 146. 18. Parent A, Hazrati LN. Functional anatomy of the basal ganglia. I. The corticobasal ganglia-thalamo-cortical loop. Brain Res Brain Res Rev 1995;20:91–127. 19. Briand KA, Strallow D, Hening W, Poizner H, Sereno AB. Control of voluntary and reflexive saccades in Parkinson’s disease. Exp Brain Res 1999;129:38 – 48. 20. Stuphorn V, Schall JD. Neuronal control and monitoring of initiation of movements. Muscle Nerve 2002;26:326 –339. 21. Fukuda M, Ghilardi MF, Carbon M, et al. Pallidal stimulation for parkinsonism: improved brain activation during sequence learning. Ann Neurol 2002;52:144 –152.

Bilateral Subthalamic Nucleus Deep Brain Stimulation in a Patient With Cervical Dystonia and Essential Tremor Kelvin L. Chou, MD,1* Howard I. Hurtig, MD,2 Jurg L. Jaggi, PhD,2 and Gordon H. Baltuch, MD, PhD, FRCS(C)3 1

Department of Clinical Neurosciences, Brown University Medical School, Providence, Rhode Island, USA 2 Parkinson’s Disease and Movement Disorders Center, Pennsylvania Hospital, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA 3 Department of Neurosurgery, Pennsylvania Hospital, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Abstract: The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well established in Parkinson’s disease, but experience with STN DBS in other movement disorders is limited. We report on a patient with medically refractory cervical dystonia and essential tremor resulting in dystonic head tremor and action tremor of the hands who obtained complete tremor suppression and near resolution of her cervical dystonia with bilateral STN stimulation. The results in this case demonstrate that STN DBS can dramatically improve dystonia and tremor in nonparkinsonian movement disorders. © 2004 Movement Disorder Society Key words: subthalamic nucleus; deep brain stimulation; cervical dystonia; tremor Deep brain stimulation (DBS) has emerged as an effective treatment for a wide range of movement disorders, including Parkinson’s disease (PD), essential tremor (ET), and dystonia. Recent research has shown that the subthalamic nucleus (STN) may play an important role in basal ganglia disorders, especially in PD, where STN stimulation improves the parkinsonian triad of rest tremor, bradykinesia, and rigidity.1 STN DBS also markedly reduces action tremor in patients with PD2 and consistently improves all manifestations of off-period dystonia.3,4 This response suggests that stimulation of the STN might also suppress tremor and dystonia seen in disorders other than PD. Although the reported experience with subthalamic stimulation in these other conditions is limited to a few case series, overall results have been promising. Of 8 patients with generalized

This article includes Supplementary Video Clips, available online at http://www.interscience.wiley.com/jpages/0885-3185/suppmat. *Correspondence to: Dr. Kelvin L. Chou, 111 Brewster Street, Pawtucket, RI 02860. E-mail: [email protected] Received 22 January 2004; Revised 8 March 2004; Accepted 20 July 2004 Published online 3 December 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20341

Movement Disorders, Vol. 20, No. 3, 2005