Lessons Learned from Open-label Deep Brain Stimulation for Tourette Syndrome: Eight Cases over 7 Years

Maria G. Motlagh; Megan E. Smith; Angeli Landeros-Weisenberger; Andrew J. Kobets; Robert A. King; Joan Miravite; Alain C. J. de Lotbinière; Ron L. Alterman; Alon Y. Mogilner; Michael H. Pourfar; Michael S. Okun; James F. Leckman

doi:10.5334/tohm.126

Figures & Tables

Table 1

Published Studies on Deep Brain Stimulation in Tourette Syndrome

Target	Study	No. Patients	Follow-up, Months	Tic Improvement (YGTSS or MRVRS), %
Midline thalamus (CM–Pf/Voi, CM–Pf)	Visser-Vandewalle (2003)5	3	12, 8, 60	90, 72, 83
	Ackermans et al. (2006)10 Ackermans et al. (2007)11	1 (CM–PF/Voi) 1 (CM–PF and postroventrolateral GPI)	12, 12	Tic 20 3 min, Tic 28 2 min
	Bajwa et al. (2007)12	1	24	66
	Maciunas et al. (2007)14	5	3	40 (Mean)
	Servello et al. (2008)17	18	3–18	65 (Mean)
	Shields et al. (2008)20	1	3	46
	Vernaleken et al. (2009)21	1	Not reported	36
	Porta et al. (2009)25 Porta et al. (2012)34	15–18	24, 60–72 long-term follow-up (same cases)	52 (Mean)41, 33, 32, 18, 1
	Servello et al. (2009)26	4	10–26	Slight to modest improvement
	Idris et al. (2010)28	1	2	Not reported
	Marceglia et al. (2010)29	7	6–24	33 (Mean)
	Ackermans et al. (2011)30	6	12	49 (Mean)
	Lee et al. (2011)32	1	18	58
	Kuhn et al. (2012)35	2	12	75 and 100
	Savica et al. (2012)36	3	12	70 (Mean)
	Maling et al. (2012)37	5	4–6	41, 33, 32, 18, 1
	Okun et al. (2013)41	5	6	19 (Mean)
GPi	Deidrerich et al. (2005)6	1	14	47–76
	Gallagher et al. (2006)9	1	Several	Disappearance of tics
	Ackermans et al. (2006)10	1 (CM–Pf and posteroventral GPi)	12	Tics 28 2/min
	Shahed et al. (2007)15	1	6	84
	Dehning et al. (2008)16	1	12	88
	Dueck et al. (2009)22	1	12	No improvement
	Martínez-Fernández et al. (2011)31	5 (one subject had both), 3 (posteroventral), 3 (anteromedial)	3–24	32, 19, 14, 63, 32, 19
	Cannon et al. (2012)33	11 (anteromedial)	4–30	51
	Dong et al. (2012)39	2 right GPi only (posteroventral)	12	59 and 53
	Massano et al. (2013)42	1 (anteromedial)	3, 12, 24	61
CM–Pf and/or GPi (anteromedial)	Houeto et al. (2005)7	1	24	82
CM–Pf and/or GPi (anteromedial)	Welter et al. (2008)18	3	20, 27, 60	65–96
GPe	Piedimonte et al. (2013)40	1	3, 6, 24	39
A/C – NA	Flaherty et al. (2005)8	1	18	25
	Kuhn et al. (2007)13	1	30	41
	Zabek et al. (2008)19	1	28	80
	Neuner et al.(2009)24	1	36	44
	Burdick et al. (2010)27	1	39	15% worse
	Sachdev et al. (2012)38	1	8	57
STN	Martinez-Torres et al. (2009) 23	1	12	76

[i] Abbreviations: A/C, Anterior Limb of Internal Capsule; CM–Pf, Centromedial–Parafascicular Complex; GPe, Globus Pallidus, Pars Externus; GPi, Globus Pallidus, Pars Internus; MRVRS, Modified Rush Videotape Rating Scale; NA, Nucleus Accumbens; STN, Subthalamic Nucleus; Voi, Ventralis Oralis; YGTSS, Yale Global Tic Severity Scale.

Table 2

Stimulation Parameters and Lead Location at Follow-up Evaluation for all Subjects

Patient	Location	Identification of the Anatomic Target	DBS Settings
1 ^a	Thalamus	Leksell frame, MRI intraoperative guidance, general anesthesia (propofol), macrostimulation used, no microelectrode recording	^*R 5-7+, 2.5 V, 210 μs, 185 Hz
	X (mm lateral AC-PC) = 5		^*L 1-3+, 2.35 V, 180 μs, 185 Hz
	Y (mm posterior AC-PC) = 4
	Z (mm beneath AC-PC) = 0
	GPi (posteroventral/sensorimotor)		^*R 5-C+, 1.0 V, 120 μs, 130 Hz
	X (mm lateral to intercommissural) = 17		^*L 1-2+, 1.0 V, 120 ∀ μs, 130 Hz
	Y (mm anterior to mid-commissural) = 4
	Z (mm deep to mid-commissural) = 5
2 ^b	Thalamus	Leksell frame, MRI intraoperative guidance, deep sedation, macrostimulation used, no microelectrode recording	NA
	X (mm lateral AC-PC) = 5
	Y (mm posterior AC-PC) = 4
	Z (mm beneath AC-PC) = 0
3 ^c	Thalamus	Leksell frame, MRI intraoperative guidance, deep sedation, macrostimulation used, no microelectrode recording	NA
	X (mm lateral AC-PC) = 5
	Y (mm posterior AC-PC) = 4
	Z (mm beneath AC-PC) = 0
4	GPi (posteroventral/sensorimotor)	Leksell frame, MRI intraoperative guidance, deep sedation, macrostimulation used, no microelectrode recording	R 2-C+, 2. 5 V, 90 μs, 185 Hz
	X (mm lateral to intercommissural) = 17		L 2-C+, 2.0 V, 90 μs, 185 Hz
	Y (mm anterior to mid-commissural) = 4
	Z (mm deep to mid-commissural) = 5
5	GPi (posteroventral/sensorimotor)	Leksell frame, MRI intraoperative guidance, deep sedation, macrostimulation used, no microelectrode recording	R 4+6-5-7+, 2.1 V, 180 μs, 185 Hz
	X (mm lateral to intercommissural) = 17		L 2-1-0-C+, 2.1 V, 180 μs, 185 Hz
	Y (mm anterior to mid-commissural) = 4
	Z (mm deep to mid-commissural) = 5
6	Thalamus	Leksell frame, MRI/CT fusion, procedure performed under local anesthesia with dexmedetomidine used for sedation	R 1-C+, 3.0 V, 90 μs, 130 Hz
	X (mm lateral AC-PC) = 5		L 1-C+, 3.2 V, 90 μs, 130 Hz
	Y (mm posterior AC-PC) = 4
	Z (mm beneath AC-PC) = 0
		Physiologic confirmation with microelectrode recording and macrostimulation
7	GPi, anterior mesial (limbic)	Leksell frame, MRI intraoperative guidance, sedation with dexmedetomidine/propofol, physiologic confirmation with microelectrodes recording only	^*R 1-C+, 3.0 V, 150 μs, 90 Hz
	X (mm lateral to intercommissural) = 14		^*L 1-C+, 2.5 V, 180 μs, 120 Hz
	Y (mm anterior to mid-commissural) = 18
	Z (mm deep to mid-commissural) = 5
	Thalamus		^*R 11-C+, 2.0 V, 60 μs, 120 Hz
	X (mm lateral AC-PC) = 6		^*L 9-10-C+, 3.0 V, 60 μs, 120 Hz
	Y (mm posterior AC-PC) = 3
	Z (mm beneath AC-PC) = 0
	GPi (posteroventral/sensorimotor)		R 8-C+, 2.5 V, 90 μs, 185 Hz
	X (mm lateral to intercommissural) = 17		^*L 8-C+, 2.5 V, 90 μs, 180 Hz
	Y (mm anterior to mid-commissural) = 4
	Z (mm deep to mid-commissural) = 5
8	Thalamus	Leksell frame, MRI/CT fusion, procedure performed under general anesthesia with propofol and remifentanil	R C+1-, 2.1 V, 90 μs, 130 Hz
	X (mm lateral AC-PC) = 5		L C+1-, 1.9 V, 90 μs, 130 Hz
	Y (mm posterior AC-PC) = 4
	Z (mm beneath AC-PC) = 0
		Physiologic confirmation with microelectrode recording and macrostimulation

Abbreviations: AC, Anterior Commissural; DBS, Deep Brain Stimulation; GPi, Globus Pallidus Pars Internus; PC, Posterior Commissural; NA: Not Applicable.

The DBS settings show right side (R), left side (L), voltage (V), pulse width (µs), and rate (Hz).

a GPi electrodes are not currently functional secondary to forceful head-snapping tics that led to electrode dysfunction.

b Electrodes were removed because of infection.

c Electrodes were removed because of lack of therapeutic benefit.

* Electrodes are currently turned OFF.

Table 3

Baseline Clinical Characteristics of the Eight Patients with Tourette Syndrome

Subject	Sex	Age (Years)	Disease Duration (Years)	Tic Symptoms	Typical Waxing and Waning Course	Self- Injury	Comorbid Disorders	Family History	Living and Work Situation	Medication Before Surgery	Current Medication
1	M	48	45	Eye blinking, violent head jerks, throwing elbow against ribs, abdominal tensing, snapping, grunting, screeching, coprolalia	No	Yes, slamming forearm against forehead	OCD (mild to moderate), depression	No	Separated, employed part time	Haloperidol, pimozide, risperidone, clonidine, fluoxetine, clonazepam, pergolide	Haloperidol, fluoxetine gabapentin, tizanidine, diazepam, temazepam, aspirin
2 ^a	M	44	41	Eye movements, facial tics, head jerking and snapping, shoulder shrugs, grunting, throat clearing	Yes	Yes, skin picking	OCD (severe)	Yes	Unmarried, self-employed	Pimozide, risperidone, olanzapine, quetiapine, fluoxetine, fluvoxamine, sertraline, clomipramine, clonazepam	Sertraline, clonazepam
3 ^b	M	37	27	Head and neck movements, body jerking, shifting body position, tongue movements, hand and arm tensing, bumping objects into teeth, toe curling, diaphragmatic dystonic tics limiting ability to breathe	No	No	OCD, attention-deficit disorder, anxiety symptoms	No	Unmarried, employed	Haloperidol, pimozide, clonidine, fluoxetine, sertraline, clonazepam	Clonidine, clonazepam,
4	M	42	38	Facial grimacing, flopping hands in front of face, pointing finger back and front, chest rubbing, grunting, yelling, whistling, curse words	No	No	OCD, history of ADHD	No	Unmarried, unemployed	Haloperidol, pimozide, clonazepam, methylphenidate	Clonazepam
5	M	24	15	Head jerks, snapping arm against side, kicking, licking items, head grabbing, copropraxia, loud screaming, sniffing	Yes	Yes, punching, hitting himself	OCD	Yes	Married, one child, unemployed	Haloperidol, pimozide, risperidone, fluphenazine, clonidine, fluvoxamine, imipramine, nortriptyline, clonazepam, pergolide	Clonazepam, quetiapine, zolpidem, topiramate, nicotine patches, ketamine, opiates
6	M	16	13	Eye blinking, head and shoulder jerking, head bobbing, flexion and extension of arms and fingers, spinning in place, throat clearing, coprolalia	Yes	No	ADHD	No	Unmarried, high-school student	Risperidone, aripiprazole, ziprasidone, sertraline, tetrabenazine, methylphenidate, topiramate	None
7	M	19	11	Dystonic posturing, exclusively left-sided tics and self-injurious behaviors such as poking left cornea and pulling on left eye lid, repeating single words or syllables	No	Yes poking left eye and pulling on left eye lid, left cheek biting	OCD, some symptoms of ADHD	No	Unmarried, unemployed	Haloperidol, risperidone, aripiprazole, fluphenazine, sertraline, clonazepam, tetrabenazine, guanfacine, topiramate, etanercept, N-acetyl cysteine	Haloperidol, clonazepam, clonidine, clonazepam, sertraline, carbamazepine
8	M	17	13	Atypical long bouts of severe tics (20 minutes to 1 hour) interspaced with long tic-free periods, tics include opening mouth wide, arm and shoulder movements, head and neck jerks, rapidly shaking head from side to side, gyrating head, arching back, flexion and extension of arms one side at a time	No	Yes, pounding of chest, punching forehead	OCD, mild depression, some symptoms of general anxiety disorder	Yes for OCD	Unmarried, student	Pimozide, risperidone, ziprasidone, aripiprazole, fluphenazine, clonidine, guanfacine, fluoxetine, clonazepam, topiramate	None

Abbreviations: ADHD, Attention-Deficit Hyperactivity Disorder; M, Male; OCD, Obsessive–Compulsive Disorder.

Positive family history: a first-degree (parent, sibling, child) or second-degree (grandparent, aunt, uncle, nephew, niece, half-sibling or a grandchild) relative with a chronic tic disorder. For additional clinical details, see Supplementary Materials.

a The electrodes removed due to side effect of infection.

b The electrodes removed due to a lack of therapeutic benefit.

Table 4

Individual Changes in Severity of Tics and Associated Behaviors in Eight Patients with Tourette Syndrome

Patients	Duration of Follow-up (Months)	YGTSS^*		YBOCS^***		HDRS		HARS
Before Surgery	At Last Follow-up^**	Before Surgery	At Last Follow-up	Before Surgery	At Last Follow-up	Before Surgery	At Last Follow-up
1	107	36	10 (72%)	29	8	10	15	0	0
2^a	95	41	32 (20%)	15	0	0	0	5	1
3^b	84	43	40 (7%)	20	27	5	4	20	15
4	51	50	40 (20%)	12	10	3	3	4	3
5	8	38	22 (44%)	0	0	4	1	5	3
6	16	46	7 (85%)	5	5	0	0	2	1
7^c	37	25	25 (0%)	0	0	3	15	3	3
8	6	43	14 (67%)	20	22	2	0	3	3

Abbreviations: HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; YBOCS, Yale–Brown Obsessive–Compulsive Scale; YGTSS, Yale Global Tic Severity Scale.

* Total tic severity does not include impairment score and is based on the worst-ever tic severity measured at the time of interview.

** Percent improvement in the YGTSS Total Tic Score.

*** Obsessive–compulsive symptom severity is based on the total obsessive–compulsive severity measured at the time of interview.

a Electrodes were removed because of infection.

b Electrodes were removed because of lack of therapeutic benefit.

c This patient does not have any vocal tics.