Abnormalities of voluntary saccades in Gilles de la Touretteʹs syndrome: pathophysiological consideration

Gilles de la Touretteʹs syndrome (TS) is a neurobehavioral disorder. Although the etiology and the pathophysiology of TS are still unknown, the involvement of the basal ganglia has long been postulated. On the other hand, saccadic eye movement was shown to be a useful measure to assess order and disorder of the function of the basal ganglia. To investigate the dysfunction of the basal ganglia of TS, we examined voluntary saccades in children with TS in comparison with the saccades in age-matched control children. Two kinds of saccades, visually-guided saccades (VGS) and memory-guided (MGS) saccades were evaluated. During the MGS, distracted saccades (DS), which indicate the distractibility, were examined. The results revealed the abnormalities in the parameters of the MGS, i.e. longer latencies and hypometric amplitudes, and decrease in the frequency of MGS. Whereas, the frequency of DS, the saccade to the predicted cue was significantly lower in younger patients (6−<9-years) than normal, but it was higher in the older TS children (9−<12-years). In addition, some of the patients showed large involuntary saccades, usually associated with eye blinks, during the task performance. These results suggest that in TS the basal ganglia fails to disinhibit the saccade neuron in the superior colliculus with the input of the frontal eye field to the striatum, and later allow the neurons to evoke non-goal directed saccades. In reference to abnormal saccades in other basal ganglia disorders with dopamine deficiency and to animal experiments with MPTP monkeys, these findings postulate primary hypodopaminergic state followed by upward regulation of dopamine receptors later in TS.