Introduction: The aim of this study is to evaluate the clinical, neurophysiological and imaging characteristics of dystonic patients with GA1 awaiting DBS.

Methods: Data from 15 children with GA1 dystonia awaiting possible DBS included neurophysiological testing of Central Motor Conduction Times (CMCTs) and Somatosensory Evoked Potentials (SEPs) using standard methodology.  14 resting-state FDG-PET scans were quantitatively analysed using Statistical Parametric Mapping (SPM12), applying a visualization threshold of p=0.001

Results: GA1 cases were characterised by the highest baseline dystonia severity with a mean Burke-Fahn-Marsden Dystonia Rating Scale-motor (BFMDRS-M) of 99.6 (SD=16.6) when compared to all other aetiologies, including Cerebral Palsy. Overall, GA1-cases responded positively to DBS at one year (Z=2.2, p=0.028), with six patients improving and one deteriorating. Neurophysiological parameters were normal in 11/15 children, one child had abnormal CMCT and three had abnormal SEP. PET imaging revealed a highly statistically significant (p<10^-5) hypometabolism within the posterior putamen extending to the posterior globus pallidus of those patients, when compared to DYT1 (n=7) cases. The finding was also consistent when comparing with other categories, indicating that this is an intrinsic characteristic of the GA1 group.

Discussion: GA1 is one of the most severely challenging childhood dystonias to manage. Our findings suggest that GA1 patients can benefit from DBS. Neurophysiology results show that the majority of GA1 children have intact motor and sensory pathways, despite extensive white matter abnormalities on MRI scans. The FDG-PET abnormalities imply an underlying functional defect in the striatum and pallidum, providing insights into the GA1 disease’s pathophysiology.