Intracortical inhibition of the motor cortex in Segawa disease (DYT5).

Abstract

Segawa disease (autosomal dominant guanosine triphosphate cyclohydrolase I [GTP-I] deficiency, DYT5) is a hereditary dopa-responsive generalized dystonia. To investigate the pathophysiologic mechanisms for dystonia in Segawa disease, we studied intracortical inhibition of the primary motor cortex in patients with Segawa disease. We studied 9 patients with Segawa disease (8 genetically confirmed patients and 1 with abnormally low GTP-I activity) and 12 age-matched normal control subjects. We studied the active motor threshold (AMT) using single pulse transcranial magnetic stimulation (TMS) and the short-interval intracortical inhibition (SICI) of the motor cortex using the previously reported paired pulse TMS method. Responses were recorded from the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. The AMT was not significantly different between the patients and normal subjects. For both studied muscles, in Segawa disease, normal amount of SICI was evoked at interstimulus intervals (ISIs) of 1 to 4 msec even though they had dystonia in those muscles. Normal SICI of the motor cortex in Segawa disease stands in remarkable contrast to the previously reported reduction of SICI in focal dystonia. This suggests that the gamma-aminobutyric acid A system of the motor cortex is intact in Segawa disease. The pathophysiologic mechanisms for dystonia must be partly different between Segawa disease and focal dystonia.