GABAA Receptor Availability Changes Underlie Symptoms in Isolated Cervical Dystonia

Abstract

GABA_A receptor availability changes within sensorimotor regions have been reported in some isolated forms of dystonia. Whether similar abnormalities underlie symptoms in cervical dystonia is not known. In the present study, a total of 15 cervical dystonia patients and 15 age- and sex-matched controls underwent ¹¹C-flumazenil PET/CT scanning. The density of available GABA_A receptors was estimated using a Simplified Reference Tissue Model 2. Group differences were evaluated using a two-sample <i>T</i>-test, and correlations with dystonia severity, as measured by the Toronto Western Spasmodic Torticollis Rating Scale, and disease duration were evaluated using a regression analysis. Voxel-based analyses revealed increased GABA_A availability within the right precentral gyrus in brain motor regions previously associated with head turning and the left parahippocampal gyrus. GABA_A availability within the bilateral cerebellum was negatively correlated with dystonia severity, and GABA_A availability within the right thalamus and a variety of cerebellar and cortical regions were negatively correlated with disease duration. While GABA_A availability changes within primary motor areas could represent a partial compensatory response to loss of inhibition within sensorimotor network, GABAergic signaling impairment within the cerebellum may be a key contributor to dystonia severity.