Structural abnormalities in the substantia nigra and neighbouring nuclei in Tourette’s syndrome

Abstract

Although midbrain nuclei (substantia nigra, ventral tegmental area, and periaqueductal grey) are considered candidate loci of pathology in Tourette's syndrome (TS), few imaging studies have examined midbrain structure. The objective of this study was to evaluate the presence of subtle structural abnormalities in the midbrain of patients with TS. High-field magnetic resonance imaging (MRI) (1.5- and 3-T) was used in 23 patients with TS and in 20 age- and sex-matched normal control subjects. Tics symptoms were rated using the Yale Global Tic Severity Scale and comorbid neuropsychiatric disorders were evaluated with standardised psychiatric rating scales. MRI scans revealed subtle structural abnormalities consistent with expanded perivascular spaces (EPVS) in the substantia nigra (compacta and reticulata) and neighbouring nuclei in 6 (26%) patients with TS, but in none of the normal control subjects (P = 0.045). Stereotyped movements were more frequent (P = 0.017) amongst TS patients with midbrain EPVS than in TS patients with normal MRI. Parkinsonism, posttraumatic stress disorder and autistic spectrum disorders exclusively occurred in TS patients with midbrain EPVS. There were no significant between-group differences in other comorbid neuropsychiatric disorders and in tics. Although EPVS are generally viewed as incidental findings, our results suggest that when EPVS are located in the midbrain they may be symptomatic. These abnormalities would reduce the actual number of neurons in specific midbrain nuclei (e.g., substantia nigra) and disrupt their connectivity with limbic, associative, and motor circuits.