Repetitive transcranial magnetic stimulation for Tourette syndrome

Study design.

The study was approved by the Joint Medical Ethics Committee of the National Hospital of Neurology and Neurosurgery. The study was a single-blinded crossover study with three different rTMS conditions that were applied in random order: left premotor (A), left motor (B), and left motor sham (C) stimulation. Conditions A, B, and C were each administered on 2 consecutive days with an interval of 2 weeks between the different treatment blocks. The entire treatment period thus consisted of six rTMS sessions over a period of 4 weeks (days 1 and 2; days 15 and 16; and days 29 and 30).

Patient selection.

Patients with GTS who were older than 18 years were recruited from the GTS Clinic at the National Hospital for Neurology and Neurosurgery run by M.M.R. The diagnosis of GTS and obsessive compulsive disorder (OCD) was made by M.M.R. according to Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., rev. criteria.4 At study entry all patients were assessed by M.M.R. The number of different motor and vocal tics was determined. Tic severity was measured using the Yale Global Tic Severity Scale.5 OCD was assessed using the Yale-Brown Obsessive Compulsive Disorder Scale (Y-BOCS).6 To screen for depression, the Beck Depression Inventory7 was carried out. Patients with a score greater than 12 were excluded. Also, patients with signs of current attention deficit hyperactivity disorder were excluded. Patients taking drugs for treatment of GTS kept their medication constant throughout the study. Based on these criteria 16 patients with GTS were studied. The mean duration between the baseline evaluation and the start of the rTMS trial was 2 months ± 0.7 SD. Patient characteristics are given in the table.

Outcome measures.

During the rTMS trial and at their final visit after completion of the study patients were followed up by one of the authors (A.M.). As a self-rating scale that patients could complete on a daily basis after each treatment session we used the Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey (MOVES), which consists of five subscales (motor tics, vocal tics, obsessions, compulsions, and coprolalia).8 Motor and vocal tic subscales and obsessions and compulsion subscales can be combined to form a tic and an obsession/compulsion subscale. Additionally, we used the hospital anxiety and depression scale. These scales were completed at baseline immediately before the first rTMS session and on days 1, 2, 3, 5, and 10 after each rTMS treatment and additionally on day 14 after the last treatment.

rTMS treatment.

Subjects were seated in a comfortable reclining chair. They were instructed to relax as much as possible but not to suppress their tics. EMG was recorded and rTMS applied as described elsewhere.9 Briefly, in the motor rTMS condition pulses were applied over the motor cortex hand area “hot spot.” The coil position for premotor rTMS was defined relative to the position of the motor hot spot for the first dorsal interosseous muscle. We defined the premotor area as 3 cm anterior to the motor cortex hand area hot spot. Single trains of 20 minutes’ duration (i.e., 1,200 pulses) were applied in each session. The intensity of rTMS was referenced to each individual’s active motor threshold,9 which was measured before and after rTMS. The intensity we used was set at 80% of active motor threshold. This stimulation intensity did not induce scalp muscle contractions. Stimulation variables were in accordance with published safety recommendations.10 For sham stimulation we used a Nostim coil (Magstim Co., Whitland, UK), which was placed over the motor cortex hand area. This coil looks identical to the figure-of-eight coil used for effective rTMS and produces similar clicking noises without producing a magnetic field. Following each treatment condition, patients were asked whether they were able to state if they had received active or sham rTMS.

Statistical analyses.

Two-factorial repeated measures analysis of variance (ANOVA) was carried out to determine the effects of the different rTMS conditions (factor “rTMS”) on MOVES, anxiety, and depression scores (factor “TIME”). The factor TIME had five levels (baseline score, the mean scores of days 1 and 2, the mean scores of days 3 and 5, score on day 10, and score on day 14 after the last rTMS treatment). The factor rTMS had three levels for premotor (condition A), motor (condition B), and sham (condition C) stimulation. For comparison of nonparametric data Wilcoxon signed rank test was used. Paired samples t-test was used for normally distributed pre- and post-rTMS interval data. For all statistical analyses a p value <0.05 was considered to be significant.

Safety.

rTMS was tolerated well. One patient reported mild headache after premotor rTMS. Two patients reported excessive tiredness after both premotor and motor rTMS lasting for about 1 day.

Clinical outcome after rTMS.

Scores on day 1 did not differ significantly from scores on day 2 and scores on day 3 did not differ significantly from scores on day 5 (Wilcoxon signed rank tests). We therefore took the mean scores of days 1/2 and days 3/5 for further statistical analyses.

In the two-factorial repeated measures ANOVA there were no effects of rTMS, no effects on TIME, and no interaction between rTMS and TIME for any of the MOVES scores.

Regarding anxiety and depression scores, two-factorial ANOVA also did not reveal an effect of rTMS or TIME on these scores and there was also no interaction between TIME and rTMS.

Blinding.

In the group of 12 patients who completed all treatment conditions only one patient correctly identified the sham stimulation condition when this was given.

TMS thresholds.

There was no significant change of active motor thresholds after any of the rTMS conditions.