Evolving concepts in the pathogenesis of dystonia

Introduction: The dystonias are a group of disorders defined by over-contraction of muscles leading to abnormal movements and postures. In recent years, enormous advances have been made in elucidating the neurobiological mechanisms responsible for many types of dystonia.

Methods: A literature review was conducted focusing on evolving concepts in dystonia genetics, anatomy and physiology.

Results: The list of genes related to dystonia has grown from a relatively small number to more than 100. Concepts regarding the neuroanatomical basis for dystonia have evolved from a relatively narrow focus on dysfunction of the basal ganglia to a broader motor network model in which the basal ganglia, cerebellum, cerebral cortex, and other brain regions play a key role. Physiologically, our understanding of the core abnormalities has matured; and numerous changes in neural signaling have been revealed in the basal ganglia, cerebellum and cortex.

Conclusion: Although the dystonias share certain clinical aspects such as over-contraction of muscles leading to abnormal movements and postures, they actually comprise a very clinically and etiologically heterogeneous group of disorders. Understanding their neurobiological basis is important for devising rational therapies appropriately targeted for specific subgroups of patients.