Table 1.

Summary of the studies in this review

Study	Target	Patients (n)	Age of surgery (years)	Subjects (ages)	Follow-up	Study Design		Outcome of Tics	Outcome of Comorbidities and Quality of life	Side effects
				< 18	< 25
Ladan et al.2017 [32]	amGPi	15	18–49	NR	NR	17–82 mo	Retrospective review	1. YGTSS 38.2% improvement motor scores 33.2% improvement vocal scores 38.2% improvement 2. 2.MRVRS 3. observed 40.5% improvement unobserved 34.1% improvement	1.OCB (Y-BOCS) (n = 15) severe OCB(n = 4) 38.7% improvement moderate OCB(n = 5) 12.3% improvement mild or subclinical OCB little or no improvement 2.Anxiety (STAI) significantly improve 3.Deprresion (BDI) significantly improve 4.GTS-QOL significantly improve	1.Stimulation-related weight gain, dizziness, feelings of nausea, freezing of gait episode, speech articulation, and akathisia
Rubens et al. 2016 [33]	CM-Pf	1	23	NR	1	18 mo	Case report	1.YGTSS 70.5% improvement impairment 60% improvement	1.Anxiety (HAS) 53% improvement	NR
Paola et al. 2016 [34]	CM-Pf	11	17–46	2	4	2–91 mo	Retrospective review	1.YGTSS 54% improvement motor scores 46% improvement vocal scores 52% improvement impairment 59% improvement	1.be employed(n = 7), enjoy an improve social life(n = 5), drive(n = 3) and go to college(n = 1)	1.Surgery-related: scalp erosion and purulent drainage 2.Postsurgical adverse effects: decreased memory, attention and mental flexibility, shock-like sensations, neck tightness, temporary anterograde amnesia, recurrent headache, nausea, vomiting, photophobia and phonophobia 3.Stimulation-induced: recurrent tension headache, worsening of pre-existing tremor, transient blurring of vision; intensity increase result dizziness and paresthesias; intensity decrease result dysarthria, involuntary movements of the tongue and jaw, and mouth opening, single seizure-like episode
Takanobu et al. 2010 [35]	CM-Pf-Voi	5	19–21	0	3	12 mo	Prospective, open-labeled case series study	1.YGTSS 52–71% improvement	1.OCD (Y-BOCS) improvement(n = 2) or exacerbation(n = 1) 2.Depression (BDI-II) improvement(n = 1) or exacerbation(n = 1) 3.Intelligence level full scale intelligence quotient score, FIQ from 64 to 82(n = 1) Performance intelligent quotient scores, PIQ from 78 ± 14 to 88 ± 13(n = 3) 4.Social impairment scores from 52 to 71% to 56–71%	1.Stimulation-related sensations of irritation, hotness of the body and blurred vision
Marano et al. 2019 [36]	CM-Pf	1	28	0	0	24 mo	Case report	1.YGTSS: sustained motor and phonic tic relief	1.OCB (SCL90), depression (BDI), and anxiety (BAI) showed a remarkable improvement	1.Stimulation-related: mild transient dysarthria and hand kinetic tremor
Richard S. et al. 2018 [37]	Medial Thalamus	13	16–33	5	12	6–58 mo	Retrospective review	1.YGTSS 50% improvement	1.OCD (Y-BOCS) (n = 12) 63% patients > 50% improvement 2.Clinical Global Impression scale much or very much improve	1.Device-related: wound erosion and infection
Daniel.et al. 2016 [38]	Ventral anterior and ventrolateral motor parts of the thalamus	8	19–56	0	2	12 mo	Retrospective open-label trail	1.YGTSS 58% improvement motor scores 51% improvement vocal scores 53% improvement impairment 60% improvement 2.MRVRS 58% improvement	1.OCD (Y-BOCS) no significant improvement 2.Depression (BDI) no significant improvement 3.Anxiety (STAI) trait anxiety significant improve state anxiety no significant improve 4.DAPP-BQ: no effect on personality dimensions of emotional dysregulation, dissocial behavior, inhibition and compulsivity 5.GAF: a significant effect on the patients’ overall level of functioning 6.Modular System for Quality of Life: significant effect on the patients’ general satisfaction with life, psychosocial quality of life, and their affective quality of life	1.Surgery-related: NR 2.Postsurgical adverse effects infection of the IPG pouch 3.Stimulation-related: weight gain, tic severity increase, consecutive deterioration of mood, disturbance of sleep, dysarthria, feelings of heaviness, heat, headache, a humming feeling during head rotation, feelings of a sudden twitch or twinge, agitation and loss of strength in one leg, numbness and tremor of the tongue, lower jaw, and cramps of the hands; intensity increase result dysarthria, disturbance of eye motility and fine motor skills; intensity decrease result disturbance of eye motility and tremor of the lower jaw
Anouk Y.J.M et al.2016 [39]	Cm-Spv-Voi; GPi	7	35–48	NR	NR	12–78 mo	Case series	1.YGTSS 27.5–88.9% improvement	NR	1.Surgery-related: vertical gaze paralysis (bleeding) 2.Postsurgerial adverse effects infection of IPG, binge eating, lethargy, dysarthria, gait disturbances and apathy 3.Stimulation-related sleeping disorders, gaze disturbances; intensity increase result reduced level of energy, minor visual disturbances, and alteration of sexual function
Zinovia et al. 2015 [40]	GPi	15	24–55	0	1	8–36 mo	Randomized, double-blind, crossover trial	1.YGTSS blinded phase (on-stimulation vs stimulation-off): 15.3% improvement baseline vs open-label stimulation phase: 40.1% improvement	Baseline vs open-label stimulation phase 1.OCD (Y-BOCS) no significant change 2.Depression (BDI) significantly improve 3.Axiety (STAI) no significant change 4.GTS-QOL significantly improve	1.Surgery-related: infection of the hardware 2.Stimulation-related deterioration of tics and hypomanic behavior
Elisabeth et al. 2012 [41]	amGPi	11	18–50	0	2	4–30 mo	Retrospective review	1.YGTSS 49.6% improvement at 3 mo motor score 48% improvement at final follow-up vocal score 56.5% improvement at final follow-up	1.OCD (Y-BOCS) (n = 9) 59% improvement at 3 months 2.Depression (HAM-D) (n = 6) 74% improvement at 3 months 3.GTS-QOL change from 39.09 to 79.09 at final follow-up 4.GAF change from 47.27 to 74.55 at final follow-up	1.Surgery-related: NR 2.Device-related lead breakage or damage, lead infection 3.Stimulation-related: anxiety with panic attacks
Perminder S. et al. 2014 [41]	amGPi	17	17–51	2	6	8–46 mo	Retrospective review	1.YGTSS 54.3% improvement motor score 47.8% improvement vocal score 51.5% improvement	1.OCD (Y-BOCS) (n = 11) change from 13.88 to 5.29 2.Depression (HDRS)(n = 8) change from 15.35 to 8.00 3.GTS-QOL change from 40.88 to 66.47 4.GAF change from 50.0 to 72.12	1.Surgery-related: NR 2.Device-related: lead breakage or damage, lead infection 3.Stimulation-related: transient anxiety, agitation, dizziness, poor balance and worsening of pre-existing stuttering, intermittent speech arrest
Johnson et al. 2019 [42]	CM thalamus; anterior GPi; posterior GPi; NA/ALIC	123	14–61	NR	NR	1–120 mo	Multisite study	1.YGTSS 46.7% improvement 2.Median time to clinical response (≥40% reduction in YGTSS) CM thalamus: 12 mo GPi:18 mo all patients: 13 mo	1.OCD (Y-BOCS) 21.1% improvement 2.Median time to clinical response (≥40% reduction in YGTSS) TS with OCD: 24 mo TS without OCD: 11 mo	NR
A.Y.J.M Smeets et al. 2016 [43]	anterior GPi	5	35–57	0	0	12–38 mo	Retrospective review	1.YGTSS motor score s64.8% improvement vocal scores 78.2% improvement 2.MRVRS motor scores 79.7% improvement vocal scores 81.0% improvement	1.Anxiety (BAI) no significant change 2.Depression (BDI) no significant change 3.ADHD (CAARS) no significant change 4.OCB (Y-BOCS) no significant change	1.Postsurgery adverse effects: infection of IPG and neck pain 2.Stimulation-related:apathy, weight loss and agitation
Hauseux et al. 2017 [44]	posteroventral GPi; posteroventral GPi + NA	3	12–18	2	3	40–69 mo	Case series	1.YGTSS motor tics improved(n = 2), vocal tics remained(n = 1) or exacerbation(n = 1), and no significant effects on tics(n = 1)	1.OCD no improvement(n = 1), exacerbation(n = 1) or recurrence(n = 1) 2.GTS-QOLmoderate(n = 2) or low score(n = 1)	1.Stimulation-related: exacerbation of phonic tics and OCD, dysarthria, recurrence of severe depressive symptoms and self-injurious behaviors
Fabian et al. 2013 [45]	GPe	1	47	0	0	6 mo	Case report	1.YGTSS 70.5% improvement	1.Anxiety (HARS) 75%improvement 2.Depression (HDRS) 82.3% improvement 3.GAF score 36.4% improvement 4.MMSE scores 17.4% improvement	1.Stimulation-related:battery depletion and loss of stimulation
Jens et al. 2008 [46]	NAc/ALIC	1	26	0	0	10 mo	Case report	1.YGTSS 20% improvement at 4 weeks 50% improvement at 10 months	NR	1.Stimulation-related: manic-like state (euphoric mood and elation, partially inappropriate behavior, overly familiar interaction patterns, restlessness, psychomotor agitation, and mild logorrhea)
Perminder Singh et al. 2012 [47]	NAc	1	32	0	0	8 mo	Case report	1.YGTSS 57% improvement at 1 month 79% improvement at 7 months	1.OCD (Y-BOCS) 90% improvement at 1 month 68% improvement at 7 months	NR
Irene et al. 2009 [48]	NAc/ALIC	1	38	0	0	36 mo	Case report	1.YGTSS 46% improvement at 3 months 44% improvement at 36 months 2.MRVRS 60% improvement at 3 months 58% improvement at 36 months	1.OCD (Y-BOCS) 53% improvement at 3 months 56% improvement at 36 months	NR
Irene et al. 2010 [49]	NAc/ALIC	1	42	0	0	36 mo	Case report	1.YGTSS 44% improvement 2.MRVRS 58% improvement	1.OCD (Y-BOCS) 56% improvement	NR
Adam et al. 2010 [50]	NAc/ALIC	1	22	0	0	30 mo	Case report	1.YGTSS 15% worsen	OCD (Y-BOCS) no significant improvement	NR
Clemens et al. 2017 [51]	Field H1 of Forel	2	19–31	0	1	6–18 mo	Case series	1.YGTSS patient 1: 91.1% improvement tic severity 82.1% improvement impairment 100% improvement patient 2: 62.7% improvement tic severity 36.4% improvement impairment 83.3% improvement	1.Depression (BDI) patient 1100% improvement patient 2 89.7% improvement 2. Anxiety (STAI) State anxiety (STAI-X1) patient 1 63.9% improvement patient 2 38.3% improvement Trait anxiety (STAI-X2) patient 1 63.8% improvement patient 2 38.8% improvement 3.OCD (Y-BOCS) patient 1 93.8% improvement patient 2 slightly reduction 4.MSQoL patient 1 53.1% improvement patient 2 43.1% improvement 5.GAF change from serious to minimal impairment	1.Stimulation-related: patient 2: worsening of tics
Irene et al. 2009 [52]	STN	1	38	0	0	12 mo	Case report	1.Tics frequency 89% improvement at 6 mo 97% improvement at 1 year	NR	NR
Domenico et al. 2016 [53]	CM-Pf-Voi, NA-ALIC, amGPi, pvGPi	37	17–57	1	8	8–32 mo	Retrospective review	1.YGTSS all patients: 42.0 reduction CM-Pf-Voi(n = 27): 47.5 reduction	1.Y-BOCS> 16 and BDI < 19(n = 7) OCD (Y-BOCS): improvement(n = 6) or slight worsening(n = 1) 2.Y-BOCS< 16 and BDI > 19(n = 6) Depression (BDI): improvement(n = 5) or exacerbation(n = 1) 3.Y-BOCS> 16 and BDI > 19:(n = 17) OCD (Y-BOCS): improvement(n = 16) or worsening(n = 1) Depression (BDI): improvement(n = 17)	1.Device-related: inflammatory reaction to the DBS system, infection, wall hematoma in the IPG pouch, skin erosion
B.Kakusa et al. 2019 [54]	CM-Pf complex+ VC/VS	1	20	0	1	12 mo	Case report	1.YGTSS 84% improvement	1.OCD (Y-BOCS) 70% improvement 2.Depression (HDRS-D17) 95% improvement	1.Stimulation-related: sensory disturbances and dizziness
Raphaëlle et al. 2018 [55]	1st: pvl GPi 2nd: ventral anterior and ventrolateral motor regions of the thalamus 3rd: radiosurgery: ventral portions of the ALIC	1	47	0	0	6 yrs	Case report	1.YGTSS 1st: no change 2nd: 69% improvement	1.OCD(Y-BOCS) 1st: 40% improvement 2nd: 40% improvement 3rd: 70% improvement 2.QIDS-SR 16 2nd to 3rd: 21 to 9 3.GAF 2nd to 3rd: 22 to 87	1.Stimulation-related: weight gain
Zhang et al. 2019 [56]	GPi and anterior capsulotomy	10	19–43	0	6	24–96 mo	Retrospective review	1.YGTSS 77% improvement motor scores 75% improvement vocal scores 78% improvement 2.CGI-SI score 71% improvement	1.OCD (Y-BOCS) 87% improvement 2.Depression (HAMD-24) 93% improvement 3.Anxiety (HAMA) 94% improvement 4.ADHD (ADHD-RS-IV) 28% improvement 5.GAF score 134% improvement 6.GTS-QQL 92% improvement	1.Stimulation-related: fatigue, laziness, confusion, disorientation; an episode of inarticulate speech and transient epileptic seizure 2.Device-related: extension wire–related infection
Zhang et al. 2019 [57]	pv GPi and capsulotomy	1	20	0	1	3 mo	Case report	1.YGTSS 53% improvement tics 45% improvement impairment 60% improvement	1.OCD (Y-BOCS) 42% improvement 2.Anxiety (BAI) 20% improvement 3.Depression (BDI-II) 62.5% improvement	NR
Anouk Y. J. M et al. 2018 [58]	anterior GPi	2	19	0	2	2 yrs	Case series	1.YGTSS patient 1: 53% improvement at 2 years motor scores 43% improvement vocal scores 60% improvement patient 2: 69% improvement at 1 year motor scores 65% improvement vocal scores 78% improvement	NR	1.Stimulation-related: patient 1: hyperkinesia, dyskinesia in the legs and a dejected mood patient 2: increased agitation, an increase in tic frequency and severity
Rene et al. 2018 [59]	CM-Pf	1	27	0	0	12 mo	Case report	1.YGTSS scheduled stimulation 33% improvement responsive stimulation 48% improvement 2.MRTRS scheduled stimulation 53% improvement responsive stimulation 64% improvement	NR	NR

Abbreviations: ADHD attention deficit hyperactivity disorder; amGPi, anteromedial or limbic, GPi ALIC anterior limb of internal capsule, BAI Beck Anxiety Inventory, BDI Beck Depression Inventory, CAARS Conner’s Adult ADHD Rating Scale, CM-Pf-Voi centromedian-parafascicular-ventro-oral internus complex, CGI-SI Clinical Global Impression–Severity of Illness scale score, DAPP-BQ Dimensional Assessment of Personality Pathology–Basic Questionnaire, FIQ Full scale Intelligence Quotient score, GAF Global Assessment of Functioning Scale, GTS-QOL Gilles de la Tourette Syndrome-Quality of Life, HARS Hamilton Anxiety Rating Scale, HDRS Hamilton Depression Scale, MMSE Mini-Mental State Examination, mo month, MRVRS Modified Rush Video-Based Rating Scale, NAc nucleus accumbens, NR not reported, OCD Obsessive-Compulsive Disorder, plGP/pvGPi/pvlGPi, posterolateral/posteroventral/posteroventrolateral, GPi, QIDS-SR16 Quick Inventory Depression Scale – Self Report 16, SCL90 Symptoms Checklist List 90, STAI State-Trait Anxiety Inventory, STN subthalamus nucleus, VC/VS ventral capsule/ventral striatum, Y-BOCS Yale-Brown Obsessive Compulsive Scale, YGTSS Yale Global Tic Severity Scale, yr year