Convergent mechanisms in etiologically-diverse dystonias

Dystonia is a neurological disorder associated with twisting motions and abnormal postures, which compromise normal movements and can be both painful and debilitating. It can affect a single body part (focal), several contiguous regions (segmental), or the entire body (generalized), and can arise as a result of numerous causes, both genetic and acquired. Despite the diversity of causes and manifestations, shared clinical features suggest that common mechanisms of pathogenesis may underlie many dystonias.

Shared themes in etiologically-diverse dystonias exist at several biological levels. At the cellular level, abnormalities in the dopaminergic system, mitochondrial function and calcium regulation are often present. At the anatomical level, the basal ganglia and the cerebellum are frequently implicated. Global CNS dysfunction, specifically aberrant neuronal plasticity, inhibition and sensorimotor integration, are also observed in a number of dystonias. Using clinical data and data from animal models, this article seeks to highlight shared pathways that may be critical in understanding mechanisms and identifying novel therapeutic strategies in dystonia.

Identifying shared features of pathogenesis can provide insight into the biological processes that underlie etiologically diverse dystonias, and can suggest novel targets for therapeutic intervention that may be effective in a broad group of affected individuals.