Treatment Options in Dystonia

Dystonia is a hyperkinetic movement disorder manifesting as involuntary muscle contractions causing abnormal posture, movements, or both. In addition to motor symptoms, a high percentage of patients with dystonia have psychiatric comorbidities, including anxiety, obsessive-compulsive disorders, and suicidal ideations. Traditionally, all forms of dystonia have been considered a basal ganglia disorder due to an imbalance of the direct and indirect pathways leading to a bottom-up decrease of intracortical inhibition and an increase in motor cortical excitability. However, advanced neuroimaging studies revealed a more complex, large-scale pattern of brain abnormalities that allowed a profound understanding of the pathophysiological mechanisms of dystonia. They are multifactorial, involving abnormal structural, functional, and metabolic brain network organization, gene association, and extrinsic/environmental risk factors. According to the current network model of the disorder, a core of alteration in the cerebellum, basal ganglia, and thalamus is common across forms of dystonia. Shared and distinct patterns of cortical abnormalities characterize instead phenotypically and genotypically forms of dystonia.

Despite the significant progress made in the past decades toward identifying genetic, cellular, and neural network re-organization underlying dystonia pathophysiology, the development of adequate treatment options is still lacking. Therapeutic options are limited primarily to temporary symptom management. Botulinum toxin injections into the affected muscles can only temporarily relieve symptoms and need to be repeated every three months; the use of off-label drugs is based on trial-and-error explorations. Invasive neuromodulation with deep brain stimulation of globus pallidus and, more recently, magnetic resonance–guided focused ultrasound thalamotomy shows therapeutic benefits. However, only a fraction of patients with dystonia undergo brain surgery. Attempts to use non-invasive neuromodulation approaches produced a significant variability in the outcome, possibly due to the absence of disorder-specific effective targets. To improve the clinical management of patients with dystonia, a recent workshop organized by the National Institute of Neurological Disorders and Stroke on research priorities stressed the need to design novel, effective therapeutic interventions based on evidence of network-level alterations in dystonia.

This Special Issue aims to provide a comprehensive understanding of current research endeavors to develop novel pathophysiologically-based treatment options for dystonia. Emphasis will be given to research studies on non-invasive and invasive neuromodulation techniques aiming at perturbing the abnormal connectivity of the motor control network to improve patients’ symptoms. We want contributors to address the following themes: non-invasive neuromodulation in dystonia, deep brain stimulation and magnetic resonance-guided focused ultrasound, and novel pharmacological options in dystonia. We welcome original articles, case reports/series manuscripts, and review papers summarizing the current state of the art on treatments in dystonia.

Keywords: Dystonia, Neuromodulation, Neurostimulation, Treatment, Neural networks