Pathophysiology of dystonia

Abstract

Pathophyiology of dystonia Alfredo Berardelli and Daniele Belvisi Dystonia is now considered a heterogeneous condition, characterized by motor and non-motor features. Several studies have clearly demonstrated that the pathophysiology of motor symptoms in dystonia is characterized by a combination of mechanisms including loss of inhibition, maladaptative cortical plasticity and deficits in sensorimotor integration, at various levels of the central nervous system. Recent evidence, however, casts doubts on the disease-specificity of these abnormalities. From an anatomical perspective, dystonia has been traditionally considered as a consequence of a cortico-basal ganglia-thalamo-cortical circuit dysfunction. Growing evidence suggests that also cerebellum may be involved in the pathophysiology of dystonia, either exerting a compensatory role or being involved in specific motor manifestations of dystonia, such as tremor. Dystonia has been recently modeled as a “network disorder” in which the clinical phenotype depends on an abnormal interaction among several neural pathways. In this complex scenario, idiopathic, inherited, and acquired forms of dystonia may have different pathophysiological mechanisms. In addition, different mechanisms and distinct neural structures seem to underlie the various forms of focal dystonia (cranial, cervical and focal hand dystonia). Patients with dystonia may also show non-motor symptoms, including cognitive, psychiatric, sleep and sensory disturbances. The pathophysiology of non-motor symptoms in patients with dystonia has been poorly investigated. The coexistence of motor and non-motor symptoms suggests that dystonia is characterized by the involvement of a wide and highly-interconnected network, that include several brain regions.