The Pathophysiology of Gilles de la Tourette Syndrome: Changes in Saccade Performance by Low-Dose L-Dopa and Dopamine Receptor Blockers

Autor: Yasuo Terao, Yoshiko Nomura, Hideki Fukuda, Okihide Hikosaka, Kazue Kimura, Shun-ichi Matsuda, Akihiro Yugeta, Francesco Fisicaro, Kyoko Hoshino, Yoshikazu Ugawa
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Brain Sciences, Vol 13, Iss 12, p 1634 (2023)
Druh dokumentu: article
ISSN: 13121634
2076-3425
DOI: 10.3390/brainsci13121634
Popis: Aim: To elucidate the pathophysiology of Gilles de la Tourette syndrome (GTS), which is associated with prior use of dopamine receptor antagonists (blockers) and treatment by L-Dopa, through saccade performance. Method: In 226 male GTS patients (5–14 years), we followed vocal and motor tics and obsessive–compulsive disorder (OCD) after discontinuing blockers at the first visit starting with low-dose L-Dopa. We recorded visual- (VGS) and memory-guided saccades (MGS) in 110 patients and 26 normal participants. Results: At the first visit, prior blocker users exhibited more severe vocal tics and OCD, but not motor tics, which persisted during follow-up. Patients treated with L-Dopa showed greater improvement of motor tics, but not vocal tics and OCD. Patients with and without blocker use showed similarly impaired MGS performance, while patients with blocker use showed more prominently impaired inhibitory control of saccades, associated with vocal tics and OCD. Discussion: Impaired MGS performance suggested a mild hypodopaminergic state causing reduced direct pathway activity in the (oculo-)motor loops of the basal ganglia–thalamocortical circuit. Blocker use may aggravate vocal tics and OCD due to disinhibition within the associative and limbic loops. The findings provide a rationale for discouraging blocker use and using low-dose L-Dopa in GTS.
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