Disruption of GABA(A)-mediated intracortical inhibition in patients with chorea-acanthocytosis

Chorea-acanthocytosis (Ch-Ac) is an autosomal recessive neurodegenerative disorder characterized by adult-onset chorea, acanthocytes in the peripheral blood, and Huntington's disease-like neuropsychiatric symptoms. Animal studies have shown mutation-related dysregulated cortical gamma-aminobutyric acid (GABA)ergic inhibitory networks in its pathophysiology. Herein we found that in patients with Ch-Ac there is a striking alteration of intracortical inhibitory circuits detected by using paired pulse transcranial magnetic stimulation protocols. Our findings show in vivo the functional disruption of GABA(A)-mediated networks in humans with Ch-Ac supporting the existing data in mice models with this condition.