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

Abstract

Background: Segawa disease (autosomal dominant guanosine triphosphate cyclohydrolase I [GTP-I] deficiency, DYT5) is a hereditary dopa-responsive generalized dystonia.Objective: To investigate the pathophysiologic mechanisms for dystonia in Segawa disease, we studied intracortical inhibition of the primary motor cortex in patients with Segawa disease.Methods: 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.Results: 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.Conclusion: 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.