Cerebellar Transcranial Direct Current Stimulation (tDCS) in Patients With Isolated Cervical Dystonia (CD)

Dystonia is a movement disorder characterized by involuntary, sustained or intermittent muscle contractions, resulting in abnormal movements and postures. CD is the most common form of focal dystonia. It is characterized by abnormal postures or movements of the head. Standard treatment in patients with CD includes regular botulinum toxin injections and physical therapy, but many patients continue to experience symptoms, especially towards the end of the treatment cycle, highlighting the need for alternative treatment options.

One of the challenges in treating CD is the incomplete understanding of its underlying neurophysiological mechanisms. Recently, CD has been recognized as a network disorder, affecting the basal ganglia, the brainstem, the sensorimotor cortex and the cerebellum. So far, there is increasing evidence supporting the role of the cerebellum in the pathophysiology of dystonia, including animal models, neuroimaging and neurophysiological studies, but the exact the role in the proposed dystonia network is only incompletely understood.

TDCS is a form of non-invasive brain stimulation modulating the excitability of superficially located neurons. CtDCS is known to modulate the excitability of neurons of the cerebellar cortex, while the cerebellar nuclei and the brain stem remain unaffected. It has been shown that anodal ctDCS increases and cathodal ctDCS decreases the excitability of the cerebellum.

This randomized and sham-controlled clinical trial aims to investigate the effects of anodal and cathodal ctDCS in CD patients, focusing on both the sensorimotor network excitability and motor symptom severity. Participants will undergo three separated experimental sessions separated by one week, each with a different stimulation condition: anodal, cathodal, and sham ctDCS. Both, the study participants and the experimenter will be blinded to the order of stimulation mode.

The outcome measures will include:

• Changes in the sensorimotor network before and after ctDCS stimulation, assessed by TMS. Measurements include four main metrics to determine the neurophysiological properties of the sensorimotor network in different ways:

• Single-pulse TMS (SP-TMS) of the left primary motor cortex, used to quantify the amplitude of motor-evoked potentials (MEPs) in response to unconditioned stimuli,
• Short-interval intracortical inhibition (SICI),
• Short-latency afferent inhibition (SAI),
• Cerebellar brain inhibition (CBI).
• Clinical motor symptom severity, assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before and after each session.

This study aims to improve the understanding of the neurophysiological mechanisms and clinical effects of ctDCS in isolated CD.

Inclusion criteria

• Clinical diagnosis of isolated cervical dystonia
• Written informed consent by the patient

Exclusion criteria

• History of other neurological disorders other than CD
• Secondary dystonia
• Severe head tremor
• Intake of centrally acting medication
• Contraindications to TMS, such as metallic implants, pregnancy and history of seizures