Abstract
In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with 99mTc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4–9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased. Our results provide substantial evidence that, in TS, brain perfusion is altered in the frontal cortex and the cerebellum and that these changes can be reversed by both GPi and CM/Voi DBS.
Highlights
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the presence of chronic, fluctuating motor and vocal tics
Stimulation of various targets, including the centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) as well as the globus pallidus internus (GPi), resulted in beneficial clinical effects with tic improvement and variable amelioration of comorbidities, such as obsessive–compulsive disorder (OCD), anxiety, and self-injurious behavior [18,19,20,21,22]
We investigated regional cerebral perfusion patterns in patients with TS compared with neuropsychiatrically healthy control subjects and during different conditions of deep brain stimulation (DBS)
Summary
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the presence of chronic, fluctuating motor and vocal tics. It is associated with an increased risk of comorbid emotional and behavioral psychopathologies, including attention deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD), which considerably affect one’s individual prognosis [1]. Neuropathological studies have reported on cellular alterations in the basal ganglia, such as an increased number of neurons in the GPi along with a reduction of quantity and density of neurons in the globus pallidus externus and nucleus caudatus [8]. Decreases in volume and microstructural changes in the thalamus have been found [9]
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