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Acute Deep-Brain Stimulation of the Internal and External Globus Pallidus in Primary Dystonia Functional Mapping of the Pallidum

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Acute Deep-Brain Stimulation of the Internal and External Globus Pallidus in Primary Dystonia Functional Mapping of the Pallidum ORIGINAL CONTRIBUTION Acute Deep-Brain Stimulation of the Internal and External Globus Pallidus in Primary Dystonia Functional Mapping of the Pallidum Jean-Luc Houeto, MD, PhD; Je´roˆme Yelnik, MD, PhD; Eric Bardinet, PhD; Laurent Vercueil, MD; Pierre Krystkowiak, MD, PhD; Vale´rie Mesnage, MD; Christelle Lagrange, PhD; Didier Dormont, MD; Jean-Franc¸ois Le Bas, MD; Jean-Pierre Pruvo, MD; Sophie Tezenas du Moncel, MD, PhD; Pierre Pollak, MD; Yves Agid, MD, PhD; Alain Deste´e, MD; Marie Vidailhet, MD; for the French Stimulation du Pallidum Interne dans la Dystonie Study Group Background: Dystonia is a syndrome characterized by trapallidal localization of the contacts of the quadri- prolonged muscle contractions that cause sustained twist- polar electrodes was performed using a 3-dimensional ing movements and abnormal posturing of body parts. atlas–magnetic resonance imaging coregistration method Patients with the severe and generalized forms can ben- by investigators blinded to the clinical outcome. efit from bilateral high-frequency pallidal stimulation. Results: Bilateral acute ventral stimulation of the GP sig- Objective: To investigate the functional map of the glo- nificantly improved the Burke-Fahn-Marsden Dystonia bus pallidus (GP) in patients with primary generalized Rating Scale score by 42% and resulted in stimulation of dystonia. contacts located in the internal GP or medullary lamina in 18 of 21 patients. Bilateral acute dorsal pallidal stimu- Design: Prospective multicenter, double-blind, video- lation, primarily localized within the external GP, had controlled study in patients treated at a university hospital. variable effects across patients, with half demonstrating slight or no improvement or even aggravation of dysto- Setting: University secondary care centers. nia compared with baseline. Patients: Twenty-two patients with primary general- Conclusions: Ventral pallidal stimulation, primarily of ized dystonia. the internal GP or medullary lamina or both, is the op- timal method for the treatment of dystonia. The varying Interventions: Acute internal and external pallidal deep- effects across patients of bilateral acute dorsal pallidal brain stimulation or pallidal deep-brain stimulation. stimulation, primarily of the external GP, suggest that unknown factors associated with dystonia could have a Main Outcome Measures: The clinical effects of acute role in and contribute to the effects of the electrical bilateral high-frequency ventral vs acute dorsal pallidal stimulation. stimulation were assessed with the Movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale. In- Arch Neurol. 2007;64(9):1281-1286 YSTONIA IS A SYNDROME ent study, we used the reversibility of elec- characterized by pro- trical stimulation and the anatomical char- longed muscle contrac- acteristic of the GP to investigate the tions that cause sustained paradox of pallidal surgery by analyzing twisting movements and the effects of high-frequency stimulation Dabnormal posturing of body parts.1 Patients applied in different areas of the GP in 22 with severe and generalized forms of dys- patients with primary generalized dysto- tonia benefit from pallidotomy2 and bilat- nia. When the posteroventral part of the Author Affiliations are listed at eral high-frequency pallidal stimula- GP is targeted for surgery using quadri- the end of this article. tion.3,4 The beneficial effects of lesioning polar electrodes, the most ventral con- Group Information: A full list or high-frequency stimulation of the glo- tacts are likely to be localized within the of the investigators of the French Stimulation du Pallidum bus pallidus (GP) have long represented internal globus pallidus (GPi) and the dor- Interne dans la Dystonie Study a paradox because, according to the model sal contacts within the external globus pal- 6 Group was published in The of basal ganglia function, the abnormal in- lidus (GPe) or its ventral border. This en- New England Journal of Medicine voluntary movements are predicted to be abled us to explore the effects of ventral (2005;332[5]:467). aggravated by pallidotomy.5 In the pres- vs dorsal electrical stimulation of the GP. (REPRINTED) ARCH NEUROL / VOL 64 (NO. 9), SEP 2007 WWW.ARCHNEUROL.COM 1281 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 1. Effects of Bilateral Ventral vs Dorsal High-Frequency Stimulation on Dystonia Motor Disability in 22 Patients With Primary Generalized Dystoniaa Before Surgery After Surgery BFM Movement Subscale Criteria (Range) Baseline Score Ventral Stimulation Score Dorsal Stimulation Score Axial (neck and trunk) (0-24) 12.7 ± 8.0 6.3 ± 6.4b 8.4 ± 6.4b Right limbs (lower and upper) (0-32) 14.1 ± 8.3 9.3 ± 6.5b 11.8 ± 8.4 Left limbs (lower and upper) (0-32) 14.7 ± 9.3 8.7 ± 7.3c 11.7 ± 9.2 Face (eyes and mouth) (0-16) 2.2 ± 2.5 0.75 ± 1.1b 1.7 ± 2.6 Speech and swallowing (0-16) 2.7 ± 3.8 1.7 ± 3.0 1.7 ± 2.8 Total score (0-110) 46.3 ± 21.1 26.7 ± 14.9c 33.6 ± 18.2b Abbreviation: BFM, Burke-Fahn-Marsden (range, 0-120, with higher scores indicating greater impairment). a Data are given as mean±SD. b PϽ.05. c PϽ.01. METHODS metric test was chosen because of the small sample size and the abnormally distributed data. Comparison of the effects of ventral vs dorsal stimulation was made using a weighted ␬ co- The study was part of the prospective multicenter French Stimu- efficient. PϽ.05 was considered statistically significant. Sta- 4 lation du Pallidum Interne dans la Dystonie Study evaluating tistical analyses were performed using the SAS 9.1 statistical the efficacy and safety of pallidal deep-brain stimulation in 22 package (SAS Institute Inc, Cary, North Carolina). patients with primary generalized dystonia. Quadripolar elec- trodes (model 3389; Medtronic Inc, Minneapolis, Minnesota) were implanted bilaterally in the posteroventral area of the GPi, iden- RESULTS tified either by stereotactic brain magnetic resonance imaging (MRI) or by MRI with ventriculography and intraoperative elec- trophysiologic guidance. The positions of the quadripolar elec- EFFECTS OF VENTRAL trodes were checked postoperatively in all patients but 1 at MRI VS DORSAL STIMULATION performed before connection of the leads to a neurostimulator (Kinetra; Medtronic Inc) placed in the subclavicular area. Lo- calization of the electrodes and each of their 4 contacts was per- Effects of ventral vs dorsal stimulation are given in formed by 2 investigators (J.Y. and E.B.), who were blinded to Table 1 and shown in Figure 1. Bilateral high- the clinical outcome, by using a 3-dimensional atlas–MRI coreg- frequency ventral pallidal stimulation significantly im- istration method, a procedure that consists of fusion of an ana- 7 8 proved by 42% the total BFM Movement subscore com- tomical atlas with the MRI for each patient. pared with preoperative status (Table 1). The BFM Twenty-two patients (11 males and 11 females; median age subscores for the neck and trunk (axial), right and left at surgery, 30 years [age range, 14-54 years]) having a clinical diagnosis of primary generalized dystonia (median age at onset, limbs, and face improved by 50%, 34%, 61%, and 65%, 8 years [age range, 5-38 years]; duration of disease, 18 years [range, respectively, whereas scores for speech and swallowing 4-37 years]) were prospectively studied. All patients underwent did not change. Overall, with stimulation of the ventral clinical evaluation, but the dorsal and ventral contacts were lo- contacts, 15 of 22 patients experienced significant im- calized in only 21 patients. The patients were evaluated preop- provement (Ͼ50% in 11 patients and 25%-50% in 4; eratively (baseline) and 1 month after surgery in 2 different con- Figure 1A), 6 demonstrated improvement of less than 20% ditions: bilateral ventral and dorsal pallidal stimulation. The ventral (Figure 1A), and dystonia slightly worsened in 1 patient. contact was defined as the most ventral contact (contacts 0 or 1 Bilateral high-frequency dorsal pallidal stimulation of the 4 contacts) that did not elicit visual adverse effects (by cur- significantly improved the total BFM movement sub- rent diffusion to the optic tract), and the dorsal contact was sys- score by 23% (Table 1). The axial subscore improved by tematically defined as contact 3. For each hemisphere, electrical parameters used for ventral or dorsal contacts were selected as 34% compared with preoperative status, but the sub- follows: pulse width, 60 to 90 µs; frequency, 130 Hz; and high- scores for the right (P=.06) and left (P=.06) limbs, est amplitude to obtain the best benefit–adverse effects ratio. The speech and swallowing, and face did not improve patients served as their own controls and were blinded to the stimu- (Table 1). Overall, with bilateral high-frequency dorsal lation conditions. They were evaluated on different days with ran- pallidal stimulation, symptoms in 4 patients improved domization of the stimulation condition (ventral or dorsal con- more than 50%; in 6, by 25% to 50%; and in 12, by less tact stimulation). The effects of stimulation on movement were than 20% (Figure 1A). In 3 patients, symptoms wors- 4 videotaped using a standardized protocol after at least 48 hours ened (data not shown). Of these 3 patients, 1 required of stimulation and were blindly assessed on the videotapes by an interruption of the stimulation condition after 7 hours of independent investigator (M.V.) using the Movement subscale dorsal test stimulation because of painful dystonic pos- of the Burke-Fahn-Marsden Dystonia Rating Scale (BFM).9 The study was approved by the ethical committee of the Salpeˆtrière turing that was worse than in the preoperative state. University Hospital, Paris, France, and all of the patients gave writ- Because the stimulation conditions were emergently ten informed consent. returned to therapeutic values on the ventral contacts, Scores at baseline and 1 month after surgery were com- the dystonia severity score could not be evaluated dur- pared using a paired Wilcoxon rank sum test.
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