Effects of deep brain stimulation on the dopamine system in patients with Tourette's syndrome

Objectives Deep brain stimulation (DBS) emerged as an accepted treament strategy for treatment resistant Tourette’s syndrome (GTS). However, there is only insufficient knowledge about the underlying physiological mechanisms. Because of the involvement of dopaminergic dysregulation in GTS, we performed an [18F]fallypride (FP) PET in order to elucidate dopaminergic DBS-effects. Due to the long scan duration in combination with the motor tic symptoms, all scans were performed under long-term anesthesia.

Methods Three patients suffering from treatment resistant GTS (2♂ both 22yrs.; 1♀, 27yrs.) underwent thalamic DBS 6 months before the PET-scans targeting the bilateral mediodorsal nuclei (2 male pat.) or the left ventrolateral nucleus (female pat. with predominant motor tics). All patients improved significantly. Two FP PET-scans have been performed under on- as well as under off-conditions (DBS). The scans have been performed under anesthesia (propofol/remifentanyl) due to tic associated head movements during the 4 hour scan procedure.

Results The D2/3-receptor availability in the target region (thalamus) decreased after turning off the stimulator (-7-18%). The unilateral left-sided thalamic stimulation caused a BPND-reduction of (-6.4%) in the left thalamus whereas the contralateral right thalamus showed an +16% increase. Compared to control subjects (without anesthesia) the baseline receptor availability was highly up-regulated (in the thalamus up to 68%).

Conclusions The BPND-reduction under "stimulator-off" conditions hints at an excess of dopamine release due to a reduced dopamine transmission during chronic thalamic stimulation. In spite of the low group size, data of the unilateral DBS depicting a spatially selective effect strengthen this hypothesis. The upregulation of FP-BPs in all three patients after 6 months of stimulation can be discussed in terms of counterregulative effects that may account for the slow process of recurrence of symptoms.

Research Support IZKF TVN6