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com
Paper
See editorial commentary,
p 111
1
Neurosurgical Division,
Functional Neurosurgery Unit,
Istituto Galeazzi IRCCS, Milano,
Italy; 2 Department of Neurology,
Tourette Centre, Istituto Galeazzi
IRCCS, Milan, Italy; 3 Institute of
Neurology, University College,
London, UK
Correspondence to:
Dr D Servello, Neurosurgical
Division, Istituto Galeazzi IRCCS,
via Galeazzi 4, 20161 Milano,
Italy; servello@libero.it
Received 8 August 2006
Revised 21 August 2007
Accepted 29 August 2007
Published Online First
10 September 2007
136
Deep brain stimulation in 18 patients with severe
Gilles de la Tourette syndrome refractory to
treatment: the surgery and stimulation
D Servello,1 M Porta,2 M Sassi,1 A Brambilla,2 M M Robertson3
ABSTRACT
Background: There have been several reports of
successful deep brain stimulation (DBS) for the treatment
of severe Gilles de la Tourette syndrome (GTS).
Method: 18 cases of GTS who were resistant to at least
6 months of standard and innovative treatments, as well
as to psychobehavioural techniques, underwent DBS. DBS
was placed bilaterally in the centromedian–parafascicular
(CM–Pfc) and ventralis oralis complex of the thalamus.
Patients were evaluated after surgery, with immediate
and formal assessments at least every 3 months,
including ‘‘on–off’’ and ‘‘sham off’’ in the first nine
patients.
Results: All patients responded well to DBS, although to
differing degrees. The duration of follow-up assessments
ranged from 3 to 18 months. The comorbid symptoms of
obsessive–compulsive behaviour, obsessive–compulsive
disorder, self-injurious behaviours, anxiety and premoni-
tory sensations decreased after treatment with DBS.
There were no serious permanent adverse effects.
Conclusions: DBS is a useful and safe treatment for
severe GTS. The results of ours and previous DBS reports
suggest that the CM–Pfc and ventralis oralis complex of
the thalamus may be a good DBS target for GTS.
Gilles de la Tourette syndrome (GTS) is charac-
terised by multiple motor tics and one or more
phonic (vocal) tics lasting longer than 1 year.1 2
Premonitory sensations occur in the majority of
cases, typically tics wax and wane, are suppressible
and suggestible, and approximately 90% of
patients have comorbid disorders, including atten-
tion deficit hyperactivity disorder, obsessive–com-
pulsive disorder (OCD) and behaviours (OCB),
self-injurious behaviours, depression, anxiety and
non-obscene socially inappropriate behaviours. The
pharmacological treatment of GTS usually includes
typical and atypical neuroleptics, clonidine, botu-
linum toxin injections3 and more recently beha-
vioural methods.
The basal ganglia are involved in models of the
pathophysiology of this disorder. The basal ganglia
interconnect the network of cortico-striato-pallido-
thalamic structures, and there are suggestions that
the pathophysiology of GTS is within these areas.4–10
Pathology at any one level of the circuitry alters
activity at all other levels of the circuit ‘‘loop’’.
However, no absolute areas have been identified as
consistently abnormal in GTS.11–13 One study used
positron emission tomography techniques, com-
bined with time synchronised audio and videotaping
of tics to demonstrate that simple motor tics appear
to be associated with the sensorimotor cortex, while
J Neurol Neurosurg Psychiatry 2008;79:136–142. doi:10.1136/jnnp.2006.104067
more complex tics (eg, coprolalia, vocal tics) were
associated with activity in pre-rolandic and post-
rolandic language regions, insula, caudate, thalamus
and cerebellum.14 The thalamus has also been
suggested to be involved in the pathophysiology of
GTS from neuroimaging15 and experimental evi-
dence,16–18 stereotactic lesions19–21 and deep brain
stimulation (DBS) surgery,22 23 which have targeted
the thalamus.
DBS has relatively recently been reported to be
successful in GTS and its associated disorders. The
Dutch–Flemish Group treated four patients (n = 1,
internal globus pallidus (GPi); n = 3, bilateral
thalamic22 24–26) while others have conducted DBS
as follows: Flaherty et al, n = 1, anterior limb of the
internal capsule, terminating in the area of the
nucleus accumbens27; Diederich et al, n = 1, GPi28;
Houeto et al, n = 1, GPi and centromedian–
parafascicular complex (CM–Pfc)23; Priori et al,
n = 1, CM–Pf bilateral thalamic29; and Sturm,
n = 3, nucleus accumbens.30 DBS has also been
used in disorders occurring frequently in associa-
tion with GTS (eg, OCD,31 anxiety32 and depres-
sion33).
We treated 18 GTS patients with DBS who were
severely affected and refractory to treatment.
Based on the fact that the presumed pathophysiol-
ogy of GTS is within the cortico-striato-pallido-
thalamic circuits and that alterations at any level
of the circuitry would be predicted to modify
activity throughout the circuit, the CM–Pfc and
the ventral oral thalamic nuclei (Voa) were the
chosen targets (CM–Pfc–Voa).
METHODS
Patients were recruited in our Tourette Clinic.
Eighteen patients (aged 17–47 years; mean 28.4
(SD 8.9) years; 15 males) satisfying DSM-IV-TR1
and World Health Organisation2 criteria for GTS,
with chronic marked to severe tics refractory to
treatment, were included in the DBS protocol. The
duration of their GTS symptomatology at DBS
was 9–39 years (table 1).
All patients were targeted at the CM–Pfc–Voa
nuclei (follow-up 3–19 months). The demographic
data and diagnostic confidence index (DCI) scores34
of the patients are shown in table 1. DCI was
calculated by two investigators separately (MP and
AB). The scores of the more senior (MP) were used
in table 1. The range of DCI scores of all patients
(AB) was 52–100% (mean 77.8 (SD 15.26)%); the
range of scores calculated by MP was 53–100%
(mean 80.2 (SD 15.4)%). The correlation was
highly significant (Pearson’s r = 0.90).
 Table 1 Demographic data of 18 patients with Gilles de la Tourette syndrome who had deep brain stimulation in the centromedian–parafascicular and ventralis oralis complex of the thalamus
Dur’n of
tics of
GTS DCI
Age at Age at prior to (lifetime Motor tics Phonic tics Drugs for tics DBS
Patient DBS tic onset DBS symptom Educat’n S = simple, S = simple, Assoc and symptoms Date of surgical
No Sex (y) (y) (y) score) (%) (y) C = complex C = complex features (ever) DBS side effects
1 M 24 5 19 83 10 S&C S&C, coprolalia OCB, aggr, SIB, Pimozide, tetra, Nov 04 No
ADHD fluvoxamine
2 M 24 4 20 77 13 S&C S&C, coprolalia OCB, aggr, SIB Clonidine, tetra, Nov 04 No
pimozide, sulpiride
3 M 47 7 39 95 12 S&C S&C, coprolalia OCB, aggr, SIB Tetra, fluvoxamine, Dec 04 No
pimozide , sulpiride
4 M 37 10 27 61 13 S S Depr Pimozide, fluvoxamine Jan 05 No
5 M 19 10 9 98 10 S&C S&C, coprolalia No Pimozide, tetra Mar 05 No
clonidine, fluvoxamine,
tiapride
6 F 28 12 16 84 13 S&C S No Haloperidol, tetra, Apr 05 No
fluvoxamine
7 M 33 10 23 73 8 S&C S&C, Coprolalia OCB, aggr, SIB Pimozide, fluvoxamine May 05 No
8 M 17 6 11 65 10 S&C S No Tetra, pimozide, May 05 No
fluvoxamine, guanfacine,
fluphenazine

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9 M 34 4 30 90 8 S&C S&C, Coprolalia OCB, aggr, SIB Tetra, pimozide, July 05 Wound healing
fluvoxamine, problems
fluphenazine
10 M 30 9 21 91 8 S&C S&C, coprolalia OCB, aggr, SIB Tetra, fluvoxamine, Sept 05 No
pimozide, clonidine
11 F 31 8 23 85 10 S&C S&C, coprolalia OCB, aggr Tetra, fluvoxamine, Oct 05 No
pimozide
12 M 46 10 36 59 13 S&C S OCB Pimozide, tiapride, Oct 05 Abdominal wall
fluvoxamine haematoma
13 M 19 7 12 100 11 S&C S&C No Tetra, fluvoxamine, Oct 05 No
pimozide, fluphenazine,
haloperidol
14 M 23 6 17 95 8 S&C S SIB Tetra, fluvoxamine, Feb 06 No
pimozide, fluphenazine
15 M 31 7 24 53 13 S&C S&C SIB, depr Tetra, fluvoxamine, Feb 06 No
pimozide, fluphenazine,
haloperidol
16 M 30 10 20 71 13 S&C S&C, coprolalia Depr Tetra, fluvoxamine, Feb 06 No
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fluphenazine, tiapride,
sulpiride
17 F 20 7 13 56 8 S&C S OCB Tetra, fluvoxamine, Mar 06 No
fluphenazine,
haloperidol, pimozide
18 M 18 6 12 99 10 S&C S&C, coprolalia SIB, aggr Tetra, pimozide, Mar 06 No
fluphenazine, sulpiride
ADHD, attention deficit hyperactivity disorder; Aggr, aggression; Assoc features, associated features; DBS, deep brain stimulation; DCI, diagnostic confidence index; Depr, depression; Dur’n, duration; Educat’n, education; GTS, Gilles de la Tourette
syndrome; OCB, obsessive–compulsive behaviour; SIB, self-injurious behaviours; Tetra, tetrabenazine.
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Neuropsychiatric assessment methods and criteria Videotaping

Inclusion criteria were: (1) satisfying diagnostic criteria for GTS; All patients were videotaped before and after DBS. Additional
(2) resistance to at least 6 months of conservative treatment recordings were performed during follow-up if the patients’
with standard and innovative treatments (for medication details symptoms increased or decreased markedly.
see table 1); (3) GTS severity resulting in disability considered to
substantially reduce the patient’s quality of life (QOL); (4) it
Surgical procedural techniques
was established that the tic symptomatology was not caused by
Preoperatively, an MRI scan of the brain (3 mm thickness, with
any other condition; and (5) all patients were deemed medically
T1 weighed axial and sagittal slices and T2 weighed coronal
fit to withstand the operation and possible sequelae.
slices) and a CT scan of the brain (after positioning of the
Assessment included full history and examination, blood
stereotactic frame) were processed by a neuronavigator (Treon;
analysis and evaluations using standardised assessment
Medtronic, Minneapolis, Minnesota, USA) to obtain the
schedules, including the Yale Global Tic Severity Rating
Scale (YGTSS)35 and a battery of neuropsychological and
neuropsychiatric schedules and cognitive tests before and after
DBS.
Patient’s impairments were also considered. Two patients
had cervical myelopathy as a direct consequence of violent tics
of the head and neck. One patient (No 12) developed cervical
disc herniation at C4–C5 requiring spinal surgery 6 months
after successful DBS. Another patient (No 15) developed
incapacitating cervical myelopathy at the C4–C5 level, and
was operated on 6 years prior to DBS. Two patients (Nos 8, 17)
were unable to eat unaided because of severe tics in the arms
and head. Prior to DBS only 7/18 patients were able to work
independently.
Exclusion criteria included psychosis, cognitive impairment,
suicide attempts, drug addiction and poor compliance with
medication. Among eight patients selected for DBS, three were
excluded (poor understanding of surgery, suicide attempt, poor
compliance, addiction) and a further five were offered DBS but Figure 1 Effects of deep brain stimulation on tics, as measured by Yale
they or their families declined. Global Tic Severity Rating Scale (YGTSS) scores.

Table 2 Yale Global Tic Severity Rating Scale scores before, and the last score after, deep brain stimulation (including follow-up, ranging from 2 to
18 months)
YGTSS Time of
DCI YGTSS YGTSS YGTSS social Total observation
Patient score YGTSS YGTSS social Total motor phonic impairment score (post DBS)
No (%) motor tic phonic tic impairment score (%) tic post tic post post post (%) (months)

1 87 18 24 50 92 9 13 30 52 17
2 99 20 19 40 79 6 7 10 23 17
3 77 23 24 50 97 6 13 20 39 16
4 58 17 16 30 63 3 4 10 17 15
5 65 15 22 40 77 7 16 30 53 13
6 74 18 15 30 63 3 3 10 16 12
7 98 21 18 50 89 4 6 10 20 11
8 68 24 24 40 88 6 11 10 27 11
9 84 21 20 50 91 5 7 10 22 9
10 81 18 18 30 66 0 7 10 17 7
11 50 17 22 40 79 4 8 10 22 6
12 100 15 14 30 59 3 0 0 3 6
13 79 20 23 40 83 10 16 20 46 6
14 51 21 24 50 95 17 17 30 64 3
15 56 23 16 40 79 5 0 0 5 3
16 65 25 17 50 92 10 3 0 13 3
17 88 23 20 30 73 6 3 20 29 3
18 99 20 20 50 90 10 16 20 46 3
Mean 19.944 19.778 41.111 80.833 6.333 8.333 13.889 28.556
SD 2.980 3.353 8.324 11.982 3.835 5.719 9.785 17.470
Pre- vs post NA 6.42 8.508 5.287 3.362
E = 11 E = 11 E = 09 E = 11
t paired p,0.001 p,0.001 p,0.001 p,0.001

DBS, deep brain stimulation; DCI, diagnostic confidence index; YGTSS, Yale Global Tic Severity Rating Scale.

138 J Neurol Neurosurg Psychiatry 2008;79:136–142. doi:10.1136/jnnp.2006.104067

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coordinates of the nuclei according to the Schaltenbrand–
Wahren atlas.36
Standard antibiotic therapy and benzodiazepines were given
prior to surgery.
A pre-coronal drill hole of 14 mm in diameter was made
under local anaesthetic. Three channel simultaneous micro
recording (high impedance, tungsten bipolar—Inomed MER
system) started from 6 mm above the target point and ended
1.5 mm below the target. Micro recording was performed every
0.5 mm, 1–2 min each, with the following parameters: 500–
5000 MHz filters, cut-off 200 mV/div, 100 ms/div sweep,
obtaining a ‘‘map’’ of neuronal activity, on the base of which
macro stimulation was made (100 Hz frequency and a 60 ms
interval, starting at 1 mAmp and gradually increasing until the
threshold of 5 mAmp was reached). All subjective impressions
reported by the patients were carefully recorded. The choice of
the trajectory of the definitive stimulating electrode (model
3387; Medtronic) was then made on the basis of these results.
Ten patients were treated under general anaesthetic either
because of the severity of tics or because they were unable to
remain immobile. In these patients, both surgical interventions
were performed under a single general anaesthetic. An MRI scan
of the brain (coronal slices, 3 mm thickness, T2 weighted)
demonstrated the correct positioning of the electrodes. All
patients maintained their routine drug therapeutic regimen
throughout surgery.
The pulse generator (Kinetra; Medtronic) was positioned in a
subcutaneous premuscular subclavicular fashion for the first
three patients and in the abdominal subcutaneous layers for
subsequent patients because of aesthetic concerns.
Follow-up protocol
Patients were admitted to the Tourette Clinic for post-
procedural management after 1 day of clinical observation
following activation of the Kinetra stimulator. Patients were
checked 1 week after discharge, and then monthly, provided no
worsening of the clinical picture occurred. Follow-up included a
visit to the clinical multidisciplinary team, care giver interview
and adjustment of drug therapy and neuroelectrical parameters
if and when required. Part of the follow-up evaluation included
a ‘‘switch on–off’’ pulse generator, performed after 6 months of
Figure 2 Postoperative inversion recovery axial MRI, superimposed on
the Schaltenbrand–Wahren Atlas.36 Electrode tips at the
intercommissural plane are shown (white circles). H1+H2, campus
forelii; Vo, nucleus ventrooralis medialis.
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follow-up. The ‘‘switch off’’ period lasted 48–72 h during which
the patients were admitted to the department.
Statistical analysis
Data were examined using SPSS (SPSS inc. V.11.5 Microsoft
Windows); t tests were used to determine significant differences
between the means of the patient scores (YGTSS) before and
after DBS. A p value ,0.05 was considered statistically
significant.
RESULTS
Duration of follow-up
The patients were followed-up clinically for 3–18 months
(table 1); the last assessments were completed at 17 months
(table 2).
Tic severity
All 18 patients responded well to DBS. The effects on tics and
social impairment are summarised in table 2 and fig 1. All four
components of the YGTSS scores improved significantly. In six
patients the improvement in tic symptomatology was progres-
sive, with only a few modifications of the stimulation
parameters (Nos 3, 4, 7, 9, 11, 12) and sustained improvement
at follow-up. The remaining 12 patients showed recurrent
motor and phonic tics after DBS, requiring several adjustments
of the stimulation parameters. In three cases (the younger
patients (Nos 5, 8, 14) and one other (No 16)), the results were
less satisfactory after 3–6 months of follow-up, with significant
spontaneous ‘‘waxing and waning’’ of symptoms. ANOVA
statistical analysis was performed. No difference between motor
and phonic tics was observed (p = 0.339).
Intraoperative results and findings
For all patients an irregular (20–40 Hz) discharge was recorded
by the three probes, with a bi-tri-phasic shape, occurring mainly
between 2 and 7 mm above the target, and then becoming
progressively less evident.
Eight patients who underwent local anaesthesia had macro
stimulation: these latter eight reported a sensation of ‘‘well
being’’ produced between 5 and 2 mm above the target. All
eight patients experienced different sensations during macro
stimulation at the three different tracks, between 5 mm and the
target, ranging from no side effects to significant drowsiness
and/or agitation. We used a three track recording, and chose the
central one because of minimal side effects. Activity patterns of
that target were recorded intraoperatively.
Neuroradiological results
We verified lead positioning with 3 mm section inversion
recovery axial MRI, superimposing on and comparing with
the Shaltenbrand–Wahren atlas.36 The first 14 patients were
studied with 1.5 T control inversion recovery MRI, demonstrat-
ing the correct positioning of the electrodes (figs 2, 3).
Stimulation parameters
The protocol stipulated that clinic visits occurred every month
in the post-DBS period. However, patients were seen more often
according to individual needs. Stimulation parameters were
modified on the basis of fluctuations in the tic symptomatology
of GTS. The frequency of the stimuli was 130 Hz in all patients,
and pulse width was maintained within the range 60–120 ms.
The pattern of stimulation and amplitude varied (2.5–4 V)
according to the symptomatology. The initial electrode setting
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discomfort in two patients. One patient developed an upward

ocular deviation at 3 V (No 17); of note is that this patient had
similar side effects with neuroleptics. Table 3 indicates the
stimulation parameters at the last follow-up visit.

Surgical adverse effects

Two patients developed adverse side effects after DBS. The first,
a 34-year-old male (No 9), developed poor healing of his scalp
scar as he felt compelled to touch it repetitively. He underwent
plastic surgery to repair his scalp skin; also, his arms and chest
were placed in a cast to prevent him from touching the scar.
This occurred again and he required a second similar cast, and
again he improved and subsequently made a good recovery. A
46-year-old male (No 12) developed an abdominal haematoma
where the pulse generator was located. The haematoma was
evacuated, and he improved within a few days.

Post-procedure pharmacological treatment

Figure 3 Postoperative inversion recovery axial MRI, superimposed on
the Schaltenbrand–Wahren Atlas.36 Slice taken 2 mm above the
intercommissural plane. White circles, electrodes; VO, nucleus
ventrooralis; CM, nucleus centralis magnocellularis; Pf, nucleus
parafascicularis.
was 0–2+, 4–6+, amplitude 2.5 V. Seven of the 13 patients (53%)
who were followed-up for 6 months or more (Nos 1, 2, 5, 8,
9,10, 13) required more frequent modifications: two (Nos 5, 13)
were stimulated with a monopolar setting (1- case+) and
required an increase in amplitude reaching up to 4 V at the last
follow-up.
Minor side effects occurred with the parameter regulations
when the intensity was .4 V. Transient subjective vertigo
occurred in almost all patients. Transient blurring of vision
occurred in four patients (Nos 1, 5, 8, 16) and abdominal
Three patients (Nos 4, 10, 12) required no medication after DBS.
The remaining 16 patients required a reduced amount and type
(25–50%) of their pre-DBS medications. After DBS, two patients
required vocal cord infiltration with botulinum toxin for severe
phonic tics.
Videotaping
Videotapes of 17/18 patients (excluding No 14) showed a
marked improvement in tic severity. In many cases, on video,
patients volunteered that their OCB and anxiety were reduced.
In one patient (No 1), walking tics remained.
‘‘On–off’’ and ‘‘sham off’’ findings
For motor and phonic tics and psychobehavioural symptoms,
after 9 months a short ‘‘on–off’’ evaluation was performed with
a blinded rater in nine patients (Nos 1–9). Eight patients (except
No 4) showed varying degrees of deterioration in the ‘‘off’’
condition, including tic reappearance, development of severe
anxiety and return of premonitory sensations and obsessional
symptoms; with ‘‘sham off’’ the patients became anxious.

Table 3 Stimulation parameters at the last follow-up visit

Patient Current stimulation Current wave Current wave width Current
No patterns amplitude (mV) (ms) frequency (Hz)

1 1-2+/5-6+ 3 120 130

2 0-2+/4-6+ 3 90 130
3 0-2+/4-6+ 3.3 210 120
4 1-c+/5-c+ 2.8 210 130
5 0-1+/4-5+ 3.5 90 130
6 1+2-/5+6- 3 210 130
7 0-2+/4-6+ 3 90 130
8 0-2+/4-6+ 3 120 130
9 0-1+/4-5+ 2.8 90 130
10 0-2+/4-6+ 2.5 90 130
11 0-2+/4-6+ 3 120 130
12 0-2+/4-6+ 3.2 120 130
13 1-c+/5-c+ 3.5 120 130
14 1-2-c+/5-6-c+ 3.5 120 130
15 0-2+/4-6+ 3.3 120 130
16 1-c+/5-c+ 3.5 120 130
17 0-2+/4-6+ 2.8 120 130
18 0-1+/4-5+ 4 120 130
Range – 2.5–4 90–210 120–130

140 J Neurol Neurosurg Psychiatry 2008;79:136–142. doi:10.1136/jnnp.2006.104067

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DISCUSSION
DBS was performed in 18 patients with GTS who were severely
affected and refractory to medication and psychobehavioural
techniques, and in whom their quality of life was substantially
reduced. All 18 responded well to DBS although to differing
degrees and all had bilateral DBS targeted at the Vo–CM–Pfc.
The safety profile was good (only 2/18 with ‘‘surgical’’ adverse
effects). The majority had some minor side effects with the
parameter regulations when the intensity was .4 V (transient
subjective vertigo, transient blurring of vision, abdominal
discomfort and in one an upward ocular deviation at even
3 V). The duration of follow-up with assessments ranged from
3 to 17 months. The comorbid symptoms of OCB, OCD,
anxiety, self-injurious behaviours and premonitory sensations
also decreased after DBS. At least half of the patients required
more frequent evaluations before achieving a good result. Motor
tics responded only apparently better than phonic tics (ANOVA
p = 0.339).
Tics did not disappear entirely. After DBS, only 3/18 patients
(ie, 16%; Nos 4, 7, 12) required no medication. All patients
received substantial support in person, on the telephone and by
email. After DBS, medication requirements in most patients
declined by half.
We chose to stimulate the thalamus (Vo–CM–Pfc complex) in
our patients on the basis that the basal ganglia appear to play a
major role in the ‘‘timing’’ and ‘‘sequencing’’ of motor and
behavioural programmes, are implicated in the pathophysiology
of GTS by neuroimaging and other experimental evidence and
have been targeted successfully in previous stereotactic and DBS
procedures.
In our patients, we did not observe any significant clinical
variations during intraoperative stimulation. We demonstrated,
by employing short ‘‘on–off’’ and ‘‘sham’’ conditions, that DBS
works well: the tics and other symptoms were obvious and
distressing when DBS was ‘‘off’’ but improved when DBS was
switched ‘‘on’’. In all but one patient, after a few seconds of
turning ‘‘off’’ the DBS, their tics and behavioural symptoms
reappeared dramatically. As with ‘‘sham off’’, all patients
developed anxiety symptoms; we felt it inappropriate to
continue ‘‘sham off’’ because of the distress and anxiety (not
increase in tics) that it caused. We therefore did no further
‘‘sham off’’. One other DBS study reported ‘‘on–off’’ DBS
testing in GTS26 and tics increased when the stimulator was
‘‘off’’.
One patient (No 1) continues to consider that GTS has a
severe impact on his life, despite a decrease in tics, well
documented by both videotape and caregiver interview. A
further patient had self-assessment visual analogue scale scores
that also indicated that he (No 14) rated his QOL at the same
level as that before DBS, despite the fact that his tics had
reduced.
We suggest that DBS in GTS patients is safe and that there are
few serious adverse effects either from surgery or the stimulation.
Surgical complications with DBS in general can exceed 25%, and
permanent neurological sequelae result in 4–6% of cases; in
Parkinson’s disease, the incidence of stroke and death in 1–5%.37–39
The low morbidity in the present patient sample may reflect the
fact that our patients were young (age range 17–47 years) and
were carefully selected. With regard to stimulation parameters
and regulation, most of our patients experienced vertigo, some
experienced abdominal discomfort, some transient blurring of
vision (at .4 V) and one had an upward deviation of the eye (at
.3 V). Transient side effects have been reported in most previous
studies. Thus Visser-Vandewalle and colleagues22 reported
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Paper
decreased energy (3/3), ‘‘well being’’ (1/3) and altered sex drive
(2/3) during stimulation as well as traction pain (2/3) from the
pulse generator. Houeto and colleagues23 reported loss of weight in
their patient, despite eating normally and having a normal
endocrine evaluation. Flaherty and colleagues27 reported that their
patient had significant mood swings (apathy, depression,
hypomania) during stimulation, but was never suicidal; these
mood swings disappeared when the stimulator was turned off.
Ackermans and colleagues26 described reduced energy at the
stimulus voltage necessary for the best effect on their tics. One
patient experienced a short sudden dystonic jerk of the whole
body each time the stimulators were switched ‘‘on’’ (during on–
off trials).26 All nine documentations to date (n = 11 patients)
suggest that DBS in GTS patients is a safe and well tolerated
procedure. Our results are in agreement with these previous
findings.
In contrast with previous reports of relatively easy DBS
regulation, we found that we had to frequently regulate
stimulation parameters for patients (7/13, 53%) who were
followed for 6 months or more (Nos 1, 2, 5, 8, 9, 10, 13), and
who required frequent modifications because of the reappearance
of symptoms. This feature was more evident in the younger
patients. This fluctuation in symptoms may be partially explained
by more recent hypotheses concerning the long term neuromo-
dulation induced by electrical stimulation.37 40
The procedure should thus be considered a symptomatic
treatment, reserved only for a few patients with marked to
severe GTS symptomatology.
At the present time, no consensus for DBS exists. Training of
surgeons and the need for a multidisciplinary team are
mandatory.39 Only carefully selected patients with severe GTS
who are refractory to medical and psychobehavioural treat-
ments and who have a markedly reduced QOL may benefit
from DBS. DBS should be undertaken only in centres that are
well acquainted with the treatment of GTS patients. Ad hoc
protocols should be constructed based on evidence.
Limitations of our study
1. We have not reported our video assessments as we did not
follow standardised procedures, as suggested by Goetz and
colleagues.41 We do have pre- and post-DBS videos, and all
demonstrate the improvement.
2. We also do not have longitudinal YGTSS scores for our
patients (ie, for 6 months prior to the study); this would
have been useful in further assessing treatment response.
CONCLUSIONS
Our results (n = 18) suggest that DBS of the Vo–CM–Pfc
complex of the thalamus and other targets can be used
successfully and safely in carefully selected patients with GTS
who are refractory to medications and psychobehavioural
treatments and who have severe symptomatology. We also
demonstrated, using both ‘‘on–off’’ and ‘‘sham’’ conditions,
that DBS is efficacious.
Acknowledgements: We would like to thank the Italian Tourette Syndrome
Association for its continuing support. MMR was supported by the National Hospital
Research Development Fund. We would also like to thank Drs Jeremy Stern and Neal
Swerdlow for their invaluable comments on the drafts of the manuscript.
Competing interests: None.
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J Neurol Neurosurg Psychiatry 2008;79:136–142. doi:10.1136/jnnp.2006.104067
 Downloaded from jnnp.bmj.com on December 4, 2013 - Published by group.bmj.com

Deep brain stimulation in 18 patients with

severe Gilles de la Tourette syndrome
refractory to treatment: the surgery and
stimulation
D Servello, M Porta, M Sassi, et al.

J Neurol Neurosurg Psychiatry 2008 79: 136-142 originally published

online September 10, 2007
doi: 10.1136/jnnp.2006.104067

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