Anterior pallidal deep brain stimulation for Tourette’s syndrome: a randomised, double-blind, controlled trial.
The Lancet Neurology. 2017-08-01; 16(8): 610-619
DOI: 10.1016/s1474-4422(17)30160-6
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1. Lancet Neurol. 2017 Aug;16(8):610-619. doi: 10.1016/S1474-4422(17)30160-6.
Epub 2017 Jun 20.
Anterior pallidal deep brain stimulation for Tourette’s syndrome: a randomised,
double-blind, controlled trial.
Welter ML(1), Houeto JL(2), Thobois S(3), Bataille B(4), Guenot M(5), Worbe
Y(6), Hartmann A(6), Czernecki V(6), Bardinet E(7), Yelnik J(7), du Montcel
ST(8), Agid Y(7), Vidailhet M(7), Cornu P(9), Tanguy A(10), Ansquer S(2),
Jaafari N(11), Poulet E(12), Serra G(13), Burbaud P(14), Cuny E(15), Aouizerate
B(16), Pollak P(17), Chabardes S(18), Polosan M(19), Borg M(20), Fontaine D(21),
Giordana B(22), Raoul S(23), Rouaud T(24), Sauvaget A(25), Jalenques I(26),
Karachi C(27), Mallet L(28); STIC study group.
Collaborators: Welter ML, Cuny E, Derkinderen P, Fontaine D, Houeto JL,
Jalenques I, Mallet L, Pollak P, Thobois S, Welter ML, Bissery A, Oya H,
Bardinet E, Yelnik J, Welter ML, Buot A, Houeto JL, Czernecki V, Jalenques I, du
Montcel ST, Tanguy A, Hajji M, Houeto JL, Mallet L, Tanguy A, du Montcel ST,
Welter ML, Karachi C, Mallet L, Welter ML, Hartmann A, Czernecki V, Yelnik J,
Bardinet E, Agid Y, Worbe Y, Dormont D, Buot A, Vidailhet M, Cornu P, Aouizerate
B, Burbaud P, Cuny E, Jalenques I, Durif F, Fauchon C, Rondepierre F, Derost P,
Aya Kombo M, Polosan M, Chabardès S, Krainik A, Krack P, Piallat B, Pollak P,
Thobois S, Guenot M, Poulet E, Klinger H, Serra G, Broussolle E, Rouaud T,
Sauvaget A, Derkinderen P, Damier P, Raoul S, Fontaine D, Borg M, Giordana B,
Magnie-Mauro MN, Houeto JL, Jaafari N, Bataille B, Ansquer S, Benatru I, Fradet
A, Dugast E, Ouerdani A, Rabois E, Quintin M, Palfi S.
Author information:
(1)Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital,
Neurology Department, Paris, France; Clinical Investigation Centre, INSERM 1127,
Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06,
Paris, France; Unité Mixte de Recherche (UMR) S1127, Centre National de la
Recherche Scientifique (CNRS), UMR 7225, Institut du Cerveau et de la Moelle
Epinière, Paris, France. Electronic address: .
(2)Department of Neurology, INSERM-Centre d’Investigation Clinique 1402,
University of Poitiers, Centre Hospitalier Universitaire (CHU) de Poitiers,
Poitiers, France.
(3)Department of Neurology C, Hôpital Neurologique, Edouard Herriot Hospital,
Hospices Civils de Lyon, Lyon, France; CNRS, Lyon Centre for Neuroscience
Research, University Lyon 1, Bron, France.
(4)Department of Neurosurgery, INSERM-Centre d’Investigation Clinique 1402,
University of Poitiers, Centre Hospitalier Universitaire (CHU) de Poitiers,
Poitiers, France.
(5)Department of Neurosurgery A, Hôpital Neurologique, Edouard Herriot Hospital,
Hospices Civils de Lyon, Lyon, France.
(6)Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital,
Neurology Department, Paris, France.
(7)Unité Mixte de Recherche (UMR) S1127, Centre National de la Recherche
Scientifique (CNRS), UMR 7225, Institut du Cerveau et de la Moelle Epinière,
Paris, France.
(8)AP-HP, Pitié-Salpêtrière Hospital, Biostatistics and Medical Informatics Unit
and Clinical Research Unit, Paris, France; Sorbonne Universités, Université
Pierre et Marie Curie Université Paris 06, UMR S1136, Institut Pierre Louis
d’Epidémiologie et de Santé Publique, Paris, France.
(9)Neurosurgery, INSERM 1127, Sorbonne Universités, Université Pierre et Marie
Curie Université Paris 06, Paris, France.
(10)AP-HP, Pitié-Salpêtrière Hospital, Biostatistics and Medical Informatics
Unit and Clinical Research Unit, Paris, France.
(11)Department of Psychiatry, INSERM-Centre d’Investigation Clinique 1402,
University of Poitiers, Centre Hospitalier Universitaire (CHU) de Poitiers,
Poitiers, France.
(12)PsyR2 Team, U 1028, INSERM and UMR 5292, Centre Hospitalier Le Vinatier,
Bron, France.
(13)Department of Neurology C, Hôpital Neurologique, Edouard Herriot Hospital,
Hospices Civils de Lyon, Lyon, France.
(14)Department of Neurophysiology, Charles Perrens Hospital, University Bordeaux
2, CNRS UMR 5543, Bordeaux, France.
(15)Department of Neurosurgery, Charles Perrens Hospital, University Bordeaux 2,
CNRS UMR 5543, Bordeaux, France.
(16)Department of Psychiatry, Charles Perrens Hospital, University Bordeaux 2,
CNRS UMR 5543, Bordeaux, France.
(17)Department of Neurology, Grenoble Alpes University, CHU Grenoble, Grenoble,
France.
(18)Department of Neurosurgery, Grenoble Alpes University, CHU Grenoble,
Grenoble, France.
(19)Department of Psychiatry, Grenoble Alpes University, CHU Grenoble, Grenoble,
France.
(20)Department of Neurology, University Hospital, Nice, France.
(21)Department of Neurosurgery, University Hospital, Nice, France.
(22)Department of Psychiatry, University Hospital, Nice, France.
(23)Department of Neurosurgery, Nantes University Hospital, Nantes, France.
(24)Department of Neurology, Nantes University Hospital, Nantes, France.
(25)Department of Psychiatry, Nantes University Hospital, Nantes, France.
(26)Department of Psychiatry, CHU Clermont-Ferrand and Clermont Auvergne
University, Equipe d’Accueil 7280, Clermont-Ferrand, France.
(27)Neurosurgery, INSERM 1127, Sorbonne Universités, Université Pierre et Marie
Curie Université Paris 06, Paris, France; Unité Mixte de Recherche (UMR) S1127,
Centre National de la Recherche Scientifique (CNRS), UMR 7225, Institut du
Cerveau et de la Moelle Epinière, Paris, France.
(28)Unité Mixte de Recherche (UMR) S1127, Centre National de la Recherche
Scientifique (CNRS), UMR 7225, Institut du Cerveau et de la Moelle Epinière,
Paris, France; AP-HP, Personalised Neurology and Psychiatry University
Department, Hôpitaux Universitaires Henri Mondor – Albert Chenevier, Université
Paris Est Créteil, Créteil, France; Department of Mental Health and Psychiatry,
Geneva University Hospital, University of Geneva, Geneva, Switzerland.
Comment in
Lancet Neurol. 2017 Aug;16(8):575-576. doi: 10.1016/S1474-4422(17)30206-5.
BACKGROUND: Deep brain stimulation (DBS) has been proposed to treat patients
with severe Tourette’s syndrome, and open-label trials and two small
double-blind trials have tested DBS of the posterior and the anterior internal
globus pallidus (aGPi). We aimed to specifically assess the efficacy of aGPi DBS
for severe Tourette’s syndrome.
METHODS: In this randomised, double-blind, controlled trial, we recruited
patients aged 18-60 years with severe and medically refractory Tourette’s
syndrome from eight hospitals specialised in movement disorders in France.
Enrolled patients received surgery to implant bilateral electrodes for aGPi DBS;
3 months later they were randomly assigned (1:1 ratio with a block size of
eight; computer-generated pairwise randomisation according to order of
enrolment) to receive either active or sham stimulation for the subsequent 3
months in a double-blind fashion. All patients then received open-label active
stimulation for the subsequent 6 months. Patients and clinicians assessing
outcomes were masked to treatment allocation; an unmasked clinician was
responsible for stimulation parameter programming, with intensity set below the
side-effect threshold. The primary endpoint was difference in Yale Global Tic
Severity Scale (YGTSS) score between the beginning and end of the 3 month
double-blind period, as assessed with a Mann-Whitney-Wilcoxon test in all
randomly allocated patients who received active or sham stimulation during the
double-blind period. We assessed safety in all patients who were enrolled and
received surgery for aGPi DBS. This trial is registered with ClinicalTrials.gov,
number NCT00478842.
FINDINGS: Between Dec 6, 2007, and Dec 13, 2012, we enrolled 19 patients. We
randomly assigned 17 (89%) patients, with 16 completing blinded assessments
(seven [44%] in the active stimulation group and nine [56%] in the sham
stimulation group). We noted no significant difference in YGTSS score change
between the beginning and the end of the 3 month double-blind period between
groups (active group median YGTSS score 68·5 [IQR 34·0 to 83·5] at the beginning
and 62·5 [51·5 to 72·0] at the end, median change 1·1% [IQR -23·9 to 38·1]; sham
group 73·0 [69·0 to 79·0] and 79·0 [59·0 to 81·5], median change 0·0% [-10·6 to
4·8]; p=0·39). 15 serious adverse events (three in patients who withdrew before
stimulation and six each in the active and sham stimulation groups) occurred in
13 patients (three who withdrew before randomisation, four in the active group,
and six in the sham group), with infections in DBS hardware in four patients
(two who withdrew before randomisation, one in the sham stimulation group, and
one in the active stimulation group). Other serious adverse events included one
electrode misplacement (active stimulation group), one episode of depressive
signs (active stimulation group), and three episodes of increased tic severity
and anxiety (two in the sham stimulation group and one in the active stimulation
group).
INTERPRETATION: 3 months of aGPi DBS is insufficient to decrease tic severity
for patients with Tourette’s syndrome. Future research is needed to investigate
the efficacy of aGPi DBS for patients over longer periods with optimal
stimulation parameters and to identify potential predictors of the therapeutic
response.
FUNDING: French Ministry of Health.
Copyright © 2017 Elsevier Ltd. All rights reserved.
DOI: 10.1016/S1474-4422(17)30160-6
PMID: 28645853 [Indexed for MEDLINE]