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Bilateral Globus Pallidus Internus Deep Brain Stimulation in Tardive Dyskinesia: A Case Report 1
2
Hazem A. Eltahawy, MD, Anthony Feinstein, Mphil, PhD, Farouk Khan, MD,3 Jean Saint-Cyr, PhD,1,3 Anthony E. Lang, MD,3 and Andres M. Lozano, MD1* 1
Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada 2 Department of Psychiatry, Sunny Brook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada 3 Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada
Abstract: The clinical response of a 53-year-old woman with tardive dyskinesia treated with bilateral globus pallidus interna deep brain stimulation is described. At 18 months follow-up, her Burke–Fahn–Marsden Dystonia Rating Scale score fell from 52 (preoperative) to 21 (60% improvement). © 2004 Movement Disorder Society Key words: globus pallidus; deep brain stimulation; tardive dyskinesia Tardive dyskinesias (TD) are abnormal involuntary movements resulting from chronic treatment with agents that block central dopamine receptors.1 The commonest movements are rapid unsustained movements described as choreic or stereotypic.2 They occur with a fairly consistent prevalence in the range of 15 to 20% of patients on neuroleptic treatment.3 Dystonic movements also occur in TD, either alone or in combination with other dyskinesias, commonly with an axial distribution in most patients.4 Recent studies suggest that high doses5 and high cumulative dose6 of neuroleptics are risk factors for TD. There is more controversy on whether the type of neuroleptics used contributes to the risk of developing TD.7,8 When neuroleptics are discontinued, TD resolves spontaneously within 3 months in approximately one third of patients but can take as long as 5 years after withdrawal to resolve.9,10 In approximately 50% of patients, symptoms may persist indefinitely.1 It remains impossible to predict which symptomatic patients will have “reversible” rather than persistent dyskinesias.2 Because of the refractoriness of TD despite discontinuation of the causative agent and in some cases the inability to stop neuroleptics because of their important therapeutic effects,
A videotape accompanies this article. *Correspondence to: Dr. Andres M. Lozano, Toronto Western Hospital, Division of Neurosurgery, 4th floor, West Wing, 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada. E-mail:
[email protected] Received 4 March 2003; Revised 23 July 2003; Accepted 12 January 2004 Published online 5 April 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20092
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alternate strategies including surgical approaches have to be considered. There have been a small number of recent reports showing promising results with pallidal surgery for refractory TD.11–14 We report here the use of bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) to treat TD.
Clinical Case Report A 53-year-old, right-handed woman had bipolar affective disorder for 27 years. She had been treated with multiple neuroleptics, including perphenazine and chlorpromazine. Her mother was known to have schizophrenia. There was no family history of movement disorders. In 1995, she developed dyskinetic movements that started in the left leg and quickly became generalized, persisting despite withdrawal of neuroleptics. At the time of referral to our movement disorder group, in 1998, her affective disorder was fully controlled. However, she was incapacitated by the movement disorder, which had not changed since 1997. Her medications at that time were lithium, clozapine, verapamil, and clonazepam. Her examination showed preserved cognitive functions apart from mild short-term memory difficulties. She was dysarthric and gave a history of swallowing difficulties. She had intermittent torticollis to the right and mild retrocollis. Her cranial nerve examination was normal. She had akathisia, marked axial and limb dystonia with bouts of axial extension and leaning to the left side, intermittent myoclonic jerking-like movements and also some fine choreiform movements of the hands (see Video, Segment 1), which were worse in the upper limbs particularly on the left side. There was mild finger to nose dysmetria possibly due to the hyperkinesia. Strength, tone, reflexes, and sensory examinations showed no significant abnormalities. During walking, she had no problems with turning but was unable to tandem gait or stand on a single foot, again possibly due to the hyperkinetic movement disorder. Her brain magnetic resonance imaging (MRI) scan was normal. Blood tests, including vasculitis screen (antinuclear antibodies, rheumatoid factor, complement level, and so on), serum copper, and ceruloplasmin, were normal. Over the next several months, multiple trials of several drug modalities resulted only in mild improvement. She had been tried on verapamil SR 240 mg/day, clonazepam 1 to 4 mg/day, diazepam 5 to 20 mg/day, benztropine, buspirone, and sodium amytal. Tetrabenazine was not used because of concern about the potential for exacerbation of her previously profoundly disabling depression. She remained on clozapine 600 mg/day and lithium 1.2 g/day. Botulinum toxin injections were also given to the face and neck muscles with little benefit. Because of the persistent dyskinesia, it was decided to proceed with surgery. The preoperative Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS)15 total score was 52. In October 1999, she underwent insertion of bilateral GPi DBS electrodes. Microelectrode recordings were used to identify the sensorimotor GPi bilaterally as previously described.16,17 The final target for the deepest contact was 20 mm lateral to the midline, 4 mm below the anterior commissure– posterior commissure (AC–PC) line at plane of the mid commissural point on the right. On the left, the position of the deepest contact was similar except that it was 3 mm anterior to the plane of mid AC–PC. Subsequent MRI confirmed location of the electrodes in the posteroventral aspect of the GPi (Fig. 1).
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FIG. 2. Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) total scores preoperatively and in progressive follow-up after surgery with the stimulator ON and OFF. Black bars, stim off; gray bars, stim on.
kinetic, requiring assistance with walking and even to keep sitting on chair, which was much worse than baseline (i.e., marked rebound dyskinesia; see Video, Segment 2). There was no change in her medications. Twelve months after surgery, rebound dyskinesias with the stimulator off were more severe, needing further adjustments in the stimulation parameters because, it was thought that higher frequency stimulation was at that point driving her dyskinesia. The parameters for her stimulator were optimized to amplitude 2.6 V, pulse width 210 sec, rate 40 Hz on both sides with contact C⫹ 2- on the right and C⫹ 2- 3- on the left side. This relatively low frequency gave the patient the best benefit from stimulation. After this modification, her speech and swallowing difficulty stabilized and her dyskinesia continued to improve; 1.5 years after the operation, her BFMDRS total score was 21 and she scored 3 on the Global Outcome Scale for dyskinesia. (In this scale, 4 ⫽ marked improvement in movement disorder and function; 3 ⫽ moderate improvement in movement disorder and function; 2 ⫽ moderate improvement in movement disorder but minimal improvement in function; 1 ⫽ mild improvement in movement disorder but no improvement in function; and 0 ⫽ no effect.18 Her serial BFMDRS scores in the follow-up visits after surgery are given in Figure 2. FIG. 1. Postoperative magnetic resonance imaging scans showing bilateral deep brain stimulation electrodes in the posteroventral part of the globus pallidus interna. A: In axial FLAIR (black arrow). B: In coronal T1.
Postoperatively, there was a gradual but significant improvement, over 3 months, in her dyskinesia especially in the axial muscles and in the lower limbs; a milder degree of facial, perioral, and cervical dystonia persisted, as did her speech and swallowing difficulties with occasional choking. The latter were unchanged when the stimulators were turned off and slightly improved when on. With the stimulator on (see Video, Segment 3), she was able perform unassisted most activities of daily living. When turned off, she would become grossly dys-
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Discussion In this report, we show a sustained benefit 18 months after bilateral GPi DBS in a patient with tardive dyskinesia/ tardive dystonia. Five other case reports have been published recently, describing stereotactic functional procedures in patients with refractory tardive dyskinesia: 2 patients had unilateral pallidotomy,11,13 1 had bilateral pallidotomies,14 1 had thalamotomy,19 and recently, a patient with tardive dystonia had bilateral pallidal and thalamic DBS.12 The results are shown in Table 1. In all six cases, there has been a sustained improvement in the severity of the dyskinesia even though it was
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TABLE 1. Outcome in five cases of TD after stereotactic procedures as reported in the literature and in the current case Study
Diagnosis
Sex
Wang et al., 199713
53
F
TD after perphenazine for chronic pain
R pallidotomy
2
Weetman et al., 199714
31
M
TD after trifluoperazine for schizophrenia
Bil pallidotomy
8
Vitek et al., 199811 Hillier et al., 199919
30
M
TD (presumed)
11
66
M
Trottenberg et al., 200112
70
F
TD after triflouperazine for bipolar affective disorder TD after fluspirilene for anxiety neuroses
Unil pallidotomy R thalamotom Bil GPi and Vim DBS
6
Current report
53
F
Bil GPi DBS
18
TD after perphenazine and others for bipolar disorder
Procedure
F. up (mo.)
Age
12
Outcome Bilateral improvement more on left, AIMS pre/post op.: 26:6 Sustained partial improvement bilaterally. BFM pre/post:76:21 Significant improvement. BFM pre/post: 31:9 Improvement mainly on the left side. AIMS pre/post op.: 36:8 Improvement only with GPi DBS, no benefit from Vim AIMS pre/post op.: 24:11 and BFM 34.5:11.5 Bilateral improvement GOS:3/4, BFM pre/post op: 52:21
TD, tardive dyskinesia; Bil, bilateral; GPi, globus pallidus interna; Vim, ventralis intermedius; DBS, deep brain stimulation; mo, month; op, operative; F. up, follow-up; AIMS, Abnormal Involuntary Movement Scale for assessment of tardive dyskinesia, max (worst) score: 42 (30); BFM, Burke–Fahn–Marsden Dystonia Rating Scale: maximum severity: 120 (15); GOS, global outcome scale for dystonia, 3 ⫽ moderate improvement in movement disorder and function, 4 ⫽ marked improvement in movement disorder and function (previously used in Yosher et al.18).
not entirely abolished. The symptoms that most commonly persisted were the orobuccal dyskinesia and cervical torticollis/retrocollis.12,14,19 This finding was observed in our patient as well. In one patient, the movements were completely abolished immediately after bilateral pallidotomy and this benefit persisted for 1 week, after which return of orofacial dyskinesia was observed.14 In our patient, the pattern of improvement was much more gradual over the course of 3 months. This is more akin to the reported postoperative course after pallidal procedures for dystonia. However, despite persistence of some abnormal movement, all the patients seem to have satisfactory functional gains enabling them to regain independence in carrying out daily life activities. Worsening of speech and swallowing is known to sometimes follow bilateral pallidal procedures. In our patient, these conditions gradually improved. Turning the stimulators on improved speech by reducing the abnormal perioral–lingual movements. The patient who had bilateral pallidotomy14 also had transient swallowing difficulty that completely resolved. In our patient, there was a noticeable rebound dyskinesia (dyskinesia much worse than before when the stimulator is switched off; see Video, Segment 2) and tolerance, which needed readjusting of the stimulation parameters to keep the clinical benefit over 18 months. Similar phenomena have been noticed with chronic thalamic stimulation for tremor.20 –24 The cause for this
finding is not understood. It has been suggested that switching off the stimulators at night sometimes limits this tolerance effect23 but in some, as in parkinsonian patients, switching off at night is difficult. The pathophysiology of tardive dyskinesia/dystonia remains unknown. Theories proposed to explain TD include excessive dopaminergic activity in the putamen secondary to neuroleptic-induced “denervation supersensitivity” of dopamine-2 receptors1 and enhanced striatal glutamatergic neurotransmission caused by neuroleptic-induced blockade of presynaptic D-2 receptors leading to striatal degeneration.25,26 These changes could produce a change in GPi and substantia nigra reticulata firing rates and patterns. The proposal of dyskinesia being mediated by a change in GPi neuronal firing is supported by the work of Filion and colleagues27 in 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) -treated monkeys and similar studies by our group28 in parkinsonian patients during intraoperative microelectrode recording. Lesioning the GPi or inactivating it by DBS seems to remove the substrate for this disordered neuronal firing pattern and, thus, prevents its propagation to the thalamocortical and brainstem circuits, hence reducing the dyskinesia.29 Acknowledgments: H.A.E. thanks Drs. A. El-Naggar and M. ElKalliny, Lake Cumberland Neurosurgical Clinic, Somerset, KY, for their help and support during his fellowship at the Toronto Western Hospital.
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CLINICAL/SCIENTIFIC NOTES Legends to the Video
Segment 1. Preoperative assessment of dystonia. The segment shows marked orofacial dyskinesia and truncal dystonia. The patient is wearing a gown and cap to allow blinded rating of videotapes. Segment 2. The patient with the stimulator off 5 months after surgery, showing rebound orofacial/axial and limb dyskinesia. Burke–Fahn–Marsden Dystonia Rating Scale total score ⫽ 54. See Figure 2. Segment 3. Patient with the stimulator turned on on the same day as video Segment 2, showing marked improvement in the facial and oral dyskinesia. Burke–Fahn–Marsden Dystonia Rating Scale total score ⫽ 32.
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