Dystonia: hopes for a better diagnosis and a treatment with long-lasting effect

Abstract

Dystonias represent a group of heterogeneous neurological conditions characterized by sustained simultaneous co-contraction of agonist and antagonist muscles in one or more sites of the body. The resultant repetitive movements and abnormal postures can affect gait and execution of voluntary movements. The pathophysiological mechanisms of dystonia remain to be fully elucidated. Not long ago, dystonia was commonly considered a manifestation of psychiatric disturbances and it has taken more than 40 years to recognize that dystonic movements originate from dysfunction within the basal ganglia circuitry. Findings from neuroimaging studies and physiological investigations clearly indicate that dystonia is associated with reduced inhibitory basal ganglia output, failure of cortical inhibition, abnormal sensorimotor integration, and maladaptive plasticity (Hallett, 2006). Over the last 20 years, many imaging studies using 18F-FDG PET, H2[15O] PET and functional MRI have been performed in patients with different types of dystonia and have revealed widespread changes in cortical and subcortical activity, both at rest and during execution of motor tasks (van Eimeren et al ., 2006; Neychev et al ., 2011). Patients with primary dystonia caused by mutations in the DYT1 and DYT6 genes and asymptomatic gene carriers of these mutations, show an abnormal resting metabolic brain network, consisting of hypermetabolism of the basal ganglia, supplementary motor area and the cerebellum (Trost et al ., 2002). Activation studies …