Table 1.
Summary of open label trials.
| Study | Target | Sample Size, Sex (Age, Years) | Follow up (Months) | Stimulation Parameters | Tic outcome (Improvement in YGTSS or MRVRS) | Comoribidity Outcome | Adverse Effects/Comments |
|---|---|---|---|---|---|---|---|
| Vandewalle et al. (1999) [20], Visser-Vandewalle (2003) [21] | CMPf, SPv Voi | Three males (42, 28, 45) | 60, 12, 8 | Bipolar all contacts 100 Hz, 210 µs, 2.4 V right, 2.2 V left; Right double monopolar 65 Hz, 210 µs, 3 V; left monopolar 100 Hz, 210 µs; Right monopolar 2.8 V, 130 Hz, 210 µs; left one monopolar 2.4 V, 100 Hz 200 µs | 90%, 72%, 83% | OCD and SIB disappeared in all 3. | A slight sedative effect in all three; 2 had increased or decreased libido. |
| Diederich et al. (2005) [41] | pvGPi | One male (27) | 14 | Monopolar 2 V, 185 Hz, 60 µs | 73% (previous YGTSS 83) | No apparent change in the mild compulsions of the patient. Significant reduction of anxiety/depression. | Small symptomatic haematoma right pallidum bradykinesia of left extremities |
| Flaherty et al. (2005) [42], Shields et al (2008) [43] | Anterior capsule CMPf, SPv Voi | One female (37), same patient operated at different target | 18, 3 | Bipolar 4.1 V, 185 Hz, 210 µs, 7 V, 90 µs, 185 Hz | YGTSS 25%, 32% | Self-injury stopped (previous retinal detachment led to blindness in one eye), but vision stabilized post DBS | Electrode breakage therefore same patient had stimulation at different target. The AC site caused altered mood and impulse control disturbance. |
| Ackermans et al. 2006 [24] | CMPf, Voi pvGpi | One male (45), one male (27) | 12 | Monopolar 6.4 V, 130 Hz, 120 µs bilaterally; Monopolar 3.1 V, 170 Hz, 210 µs bilaterally | Tics 20 to 3/min, Tics 28 to 2/min | Obssessions and compulsions (measured by the revised Padua inventory) improved by 62% in the ON than OFF condition | CMPf patient is the same as in Vandewalle study- he experienced vertical gaze palsy and decreased libido. Both patients complained of reduced energy. |
| Kuhn et al. 2007 [44] | NAC, internal capsule | One male (26) | 30 | Tetra monopolar 90 µs, 130 Hz, 7 V | 41% with YGTSS, 50% MRVRS (Previous YGTSS 90 and MRVRS 18) | Reduction in SIB, reduction in OCD by 52% based on Y-BOCS | No significant adverse effects |
| Bajwa et al. 2007 [25] | CMPf, SPv Voi | One male (48) | 24 | Bipolar 2 V, 130 Hz and 90 µs | 66% (Previous YGTSS score 35.5 and overall 83) | YBOCS improved 75% | Approximately 14 programming sessions required over 2 years. No serious adverse effects. |
| Shahed et al. 2007 [45] | pvGPi | One male (16) | 6 | Monopolar 5 V, 160 Hz right, 145 Hz left, 90 µs | 84% (YGTSS) | YBOCS improved 69% (only obsessions not compulsions). | No surgical adverse effects |
| Dehning et al. 2008 [46] | pvGPi | One female (44) | 12 | Monopolar 4.2 V, 145 Hz, 210 µs | YGTSS 88% | Patient did have SIB including self-biting and beating but outcome not reported. | Complaints of depression. Vertigo and stomach aches in first few months. No serious adverse effects. |
| Zabek et al. 2008 [47] | Right NAC | One male (31) | 28 | Not reported | 80% (15-minute videotaped exams) | None reported | Unilateral right side only. |
| Neuner et al. 2009 [48] | NAC | One male (38) | 36 | Double monopolar 6 V, 145 Hz, 90 µs | YGTSS 44% mRVTRS 58% | YBOCS 56% | Rapid IPG depletion-2 replacements in 36 months. Incidental finding was that patient no longer wanted to smoke. |
| Dueck 2009 [49] | pvGPi | One male (16) | 12 | Monopolar 4 V, 130 Hz, 120 µs | No improvement | Co-morbidity was severe mental retardation which was not affected | Not reported |
| Servello et al. 2008 [22] | CMPf Voi | 15 males, 3 females (17–47) | 3-18 | Bipolar 2.5–4 V, 90–120 µs, 130 Hz | YGTSS 65% | None reported | Transient stimulation induced vertigo, poor scalp incision healing due to repetitive touching requiring body shield. |
| Servello et al. 2009 [50] | CMPF + ALIC/NA in 3, 1 had only ALIC/NA | Three males, one female (25, 31 ,37, 47) | 10–26 | 3 monopolar, 1 bipolar 4–4.5 V, 130–160 Hz, 150–180 µs | Variable, mostly slight improvement in tics | Sight improvement in OCD | None reported |
| Servello et al. 2010 [26] | Total 79 procedures 36 patients) CMPf/Voi (67) pvGPi (2)ALIC-NA (10) | 25 males, 6 females (17–57). 4 additional patients received leads in multiple targets and one in ALIC/NA | 3–48 | At last follow up 2–5 V, 90–140 µs, 60–180 Hz | YGTSS 47% mean improvement | 17% mean improvement in YBOCS | 2 patients had stimulator switched off, reporting unsatisfactory results, 2 had surgical revision of pulse generator due to infection, and one had hardware failure. |
| Martinez-Torres et al. 2009 [51] | STN | One male (38) | 12 | Monopolar 3 and 3.2 V, 130 Hz, 60 µs | 76% | Not reported | Patient also had Parkinson’s disease which was the indication for DBS in STN |
| Martinez-Fernandez et al. 2011 [52] | pvGPi (2), amGPi (2), pvGPi (1) (then changed to anteromedial region after 18 months) | 4 males (21–60), 1 female (35) | 3–24 | PL GPi: Monopolar 2.5 V, 150 µs, 170 Hz, 2.5 V, 60 µs, 130 Hz; AM GPi: Monopolar 4.2 V, 60 µs, 160 Hz, Monopolar 4 V, 210 µs, 130 Hz; PL then AM GPi: Bipolar 3.6 V, 60 µs, 20 Hz for both | Anteromedial group: MRVRS 54% , Posterolateral group (3 patients, with one experiencing worsening symptoms and responders average 37% improvement). YGTSS 38% improvement versus 20% for amGPi and pvGPi. | YBOCS mean change of 26% at last follow up | Complaints of agitation in 1, anxiety in 2, weight gain in 1, infection in 1 requiring repeat removal of battery. |
| Idris et al. 2010 [27] | CMPf, Voa | 1 male (24) | 2 | 3.5 V, 120 µs, 130 Hz | No scales reported, but tics noted to improve | Not reported | Postoperative bilateral subcortical haematomas attributed to low factor XIIIA |
| Ackermans et al. 2010 [28] | CMPf, SPv, Voi | 2 males (42,45) | 72–120 | Amplitude L1, 8 R1, 5 130 Hz, 90 µs Amplitude L8, 5 R8, 5 100 Hz 150 µs At long-term follow up | Patient 1 (5 years) tic improvement 90.1%, maintained at 10 years (92.6%). In patient 2, after 8 months 82% slightly decreased at 6 years (78%). Video tic rating scale used measuring vocal and motor tics/10minutes. | Not reported, but in one patient “psychopathology“ reported to remain. Compulsions said to have disappeared in both patients. In one patient with depression, only slight decrease after surgery. | Both patients reported reduced energy. Both experienced traction of the lead in neck. One patient experienced a decrease in erectile function whilst the other had increased sexual drive. Both reported some visual blurring. One patient reported decreased verbal fluency and learning. |
| Burdick et al. 2010 [53] | ALIC/NA | One male (33) | 30 | Not reported | YGTSS 15% reduction at 6 months and thereafter until 30 months of last follow up remained unchanged. Initially had mild tics with a pre-operative MRVRS score of 5. | Not reported | No reported adverse effects. |
| Kaido et al. 2011 [19] | CMPf | One male (20) ,two females (19, 21) | 14–21 | Tetrapolar bilateral 2.3 V, 210 µs, 130 Hz; Tetrapolar Left 2.1 V, right 2.3 V, left 210 µs, right 180 µs, 130 Hz; bilaterally Tripolar Right 2.6 V, left 2.5 V, 180 µs, 80 Hz | Tics (52%–71%) Social impairment (56%–71%) | Not reported | No reported side effects. |
| Kuhn et al. 2011 [29] | Vop-Voa-Voi (unilateral) | One male (39), one female (27) | 12 | Bipolar 4.5 V, 130 Hz, 120 µs; Bipolar 3.1 V, 90 Hz, 120 µs | YGTSS 75%–100% MRVRS 77%–100% | BDI-no negative impact | Reduced verbal fluency at one year in both patients. |
| Dehning et al. 2011 [54] (one patient previously reported in Dehning 2008 [46]) | pvGPi | Three females (25–44), one male (38) | 5–13 | 4.2 V, 4 V, 3.8 V; 210 µs, 150 µs, 150 µs, 145 Hz, 130 Hz, 130 Hz (3 females) 3.5 V, 180 Ms, 130 Hz | 2 patients responders (64% and 88% improvement YGTSS) 2 patients non-responders 1 female 2 male | Not reported | Lead revision was done in a non-responder without improvement. |
| Dong et al. 2012 [55] | pvGpi (unilateral R) | Two males (41, 22) | 12 | Quadripolar, 3.5 V, 2.8 V, 90 µs, 160, 130 Hz | YGTSS 53.1%–58.5% | None reported | No apparent adverse effects. |
| Cannon et al. 2012 [56] | amGPi | 8 males (22–50), 3 females (18–34) | 4–30 | Quadripolar, initial stimulation 1 V, 60 µs, 130 Hz, adjusted at follow ups | YGTSS motor 48% vocal 56.5% | Mean YBOCS reduction 59%, HDRS 74%, GTS-QLS 102% | Complications from hardware malfunctions in 3 (due to SIB, MVA, and unknown). 1 patient did not tolerate DBS and switched it off. Anxiety in 2 patients |
| Duits et al. 2012 [30] | CM-Spv-Voi | One male (21) | 23 | Not reported | YGTSS- worse with DBS Pre-op-42 Stim OFF-12 Stim on-39 | Y-BOCS Pre-op: 20 Stim OFF-8 Stim ON-7 | Severe post-operative complications including psychogenic paroxysmal hypertonia.The patient may have had a somatoform disorder, that may contra-indicate DBS. |
| Savica et al. 2012 [31] | CMPf | 2 males, one female (17, 17, 35) | 1 | 17 years old males: Bipolar 3.7 V, 120 µs, 117 Hz; Monopolar 2.5 V, 90 µs, 130 Hz. 35 years old female: Bipolar 4.1 V, 120 µs, 107 Hz | YGTSS 70% mean improvement | No formal assessment, but co-morbid symptoms appeared stable or slightly improved. | Adverse effects related to stimulation such as mild paraesthesias but corrected with programming changes. |
| Okun et al. 2013 [32] | CM (scheduled stimulation) | 3 females, 2 males (28–39) | 6 | Not reported | YGTSS 19% mean improvement mRVRS 36% mean improvement | YBOCS, HDRS, QOLAS did not improve. | No serious side effects. |
| Porta et al. 2012 [23] | Cm-Pfc-Voa | 15 male, 3 females (17–47) | 5–6 years | 2.5–4 V, 60–120 µs, 130 Hz | YGTSS 73% | YBOCS 42% (p = 0.003), STAI-46%, BDI−55% | One patient developed poor healing of scalp scar due to compulsion to touch, the other developed abdominal haematoma where pulse generator was located. Majority had some minor side effects if voltage> 4 such as vertigo or blurring of vision. |
| Motlagh et al. 2013 [33] | Midline thalamic | 4 males (16–44) | 6–95 | 0.1–5 V, 60–120 µs, 60–200 Hz (4 bipolar one tripolar) | YGTSS- Greater improvement in the 2 younger patients (67%–85%), compared to older patients (7%–20%). | YBOCS-100% improvement in on patient but minimal change or worsening in others, HDRS and HARS-no change | 44 year old male picked compulsively at chest and cranial incisions so DBS was removed due to infection. 42 year old male had DBS system removed due to lack of therapeutic effect. |
| Dong et al. 2014 [57] | pvGpi | 1 male (33) | 39 | Monopolar 2.8 V, 90 µs, 130 Hz (frequency then reduced to 65 Hz 33 months) | YGTSS 92.9% at 33 and 39 months | YBOCS went from 18 to 0HAS and HDS markedly reduced | Supports that low frequency stimulation may be an optional therapeutic strategy in some patients |
| Zhang et al. 2014 [58] | pvGpi | 12 males (16–34), 1 female (21) | 13–80 | Not reported | YGTSS Mean 52.1% (13–80 months). | GTS-QOL improved by a mean of 45.7% (range, 11.0%–77.2%). | Not reported |
| Sachdev et al. 2014 [59] | amGPi | 14 males, 3 females (17–51) | 8–46 | Mean at follow up: 4.14 V, 95.2 µs, 139.4 Hz | Overall 48.3% reduction motor tics, 41.3% in phonic, 1 month 70.6% of patients had >50% reduction in YGTSS | YBOCS average 62% improvement (p = 0.001), 39% improvement in GTS-QOL (p < 0.001) | Lead breakage in 4 patients, one patient had infection, 2 transient anxiety, 1 dizziness, 1 poor balance. |
| Huasen et al. 2014 [60] | amGPi | One female (19) | 12 | Bipolar 2.9 V, 180 Hz, 180 µs | YGTSS 55% improvement | Not formally assessed | Patient had a cervical cord contusion secondary to violent cervical tics, with DBS used to preserve limb function and led to improvement in her neck extension tics |
| Zekaj et al. 2015 [38] | CMPf, Vo | 1 male (17) | 84 | Not reported | At 12 months YGTSS 58.2% | Not reported | 5 years post surgery DBS removed, and patient had stabilized despite stimulation. 2 year later continues stable. Symptoms may have resolved spontaneously. However, supports DBS in younger patients. |
| Huys et al. 2016 [34] | Ventro- anterior and ventrolateral motor parts of thalamus | Three female, five male (19–56) | 12 | 1.3–3.7 V, 80–130 Hz, 60–150 µs | YGTSS and mRVRS at last follow up average 58% | In 5 no OCD at baseline, 2 mild and 1 severe. No significant effect on OCD comorbidity. Significant effect on quality of life improvement. | One patient had mild infection of subcutaneous pulse generator one patient had disturbance of eye motility, tremor of lower jaw. 1 patient had suicidal thoughts, 1 dysarthria. |
| Smeets et al. 2016 [61] | Anterior GPi | Three males and two females (35–57) | 5–38 | Tetrapolar 2.2–5.6 V, 180-360 µs, 100–180 Hz | YGTSS 71.5% average | In the three patients with baseline OCB (12%, 35% and 100%). | Two males had previous CMPf stimulation but due to side effects such as gaze disturbance, switched to GPi after 6 and 8 years after infection with IPG replacement. Other adverse effects included apathy in 2 patients, weight loss and agitation in 1 patient |
| Cury et al. 2016 [35] | CMPf | One male (23) | 18 | Not reported | YGTSS 70.5% Subscore impairment 60% | Patient did not have OCD 53% improvement on hospital anxiety scale (HAS) | None reported |
| Servello et al. 2016 [36], Testini et al. 2016 [37] | Vo-Cm-Pf-30, Vo-Cm-Pf and NA-ALIC-2, NA-ALIC (in 3 patients as single target, 3 as rescue therapy) amGPi (1 patient and 2 as rescue) CMPf | 14 females, 34 males (total 48), 37 included in final analysis (17–57) 18 males, 3 females (17–46) | Up to 4 years 2–91 | 130 Hz initally in all patients, 60–120 µs, 2.5–4.5 V Bilateral quadripolar, specific parameters not reported | For remaining 37 patients Mean postoperative decrease in YGTSS 63% Reduction of more than 50% seen in 78.4% patients Average YGTSS 54% (46% motor, 52% vocal and 59% impairment). All but two patients reported marked reduction in tic severity and quality of life | 35 OCD, 25 both OCD and depressive disorder. In 4 patients with moderate/severe depression, BDI improved by 45%, in the other 2 only slightly or inconsistently. All patients had psychiatric co-morbidities but outcome not reported. | In 11 patients the device was removed due to inflammatory complications or poor compliance and these were not included in final analysis. NA-ALIC was the single target in 3 patients, joint target in another 3, and rescue for further 3 patients. PvGPi targeted in one patient who then required rescue surgery in NA-ALIC. 12 patients had skin erosions requiring surgical intervention. 1 patient underwent wound revision due to scalp erosion and wound infection. Three years before, one patient had pallidal DBS with no apparent benefit. Postsurgical adverse effects reported on neuropsychological evaluation included occipital headache, and memory loss (including temporary anterograde amnesia) |