Noninvasive Brain Stimulation for Cervical Dystonia

Cervical dystonia (CD) is the most common form of dystonia and is characterised by excessive and involuntary muscle contractions of the muscles in the neck. Whilst botulinum neurotoxin (BoNT) injections to the affected muscles can provide therapeutic relief to CD patients, up to one-third of patients report an inadequate response to treatment. In more severe cases, deep brain stimulation (DBS) of the globus pallidus interna (GPi) or subthalamic nucleus is an effective treatment for CD symptoms, directly and indirectly modulating networks thought to be abnormal in CD. TMS trials have previously been conducted to investigate its potential to ameliorate CD symptoms. These studies have shown limited success, with small sample sizes, and variable results. A major factor limiting the more effective use of TMS in CD is that it is not yet known where to target with TMS, given the many structures implicated in the neurobiology of the disorder. A prior study using lesion network mapping in CD attempted to address this issue by localising a brain network connected to lesions causing CD. Corp, et al. demonstrated that although causal lesions were located throughout the brain, all lesions were functionally connected to a brain network involving positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex (S1). Preliminary work from our group examined the effect of targeting this lesion network mapping-derived S1 cluster using TMS. First, a single session of continuous theta-burst stimulation (cTBS) to the S1 indicated target engagement, as demonstrated by abnormal metabolic response in CD patients, and next, a pilot trial of 10 days of daily cTBS demonstrated a 12% reduction in CD symptoms. The primary aim of this study is to assess whether a higher-dose of (4x daily) cTBS can increase therapeutic effect.

Inclusion criteria

• Aged between 18 and 85 years
• Diagnosis of idiopathic cervical dystonia made by an expert physician
• Last botulinum toxin injection administered at least two months before the start of participation in the study (Albanese, Abbruzzese et al. 2015)

Exclusion criteria

• Head or neck trauma occurring less than 12 months before the onset of dystonia
• Acquired dystonia (e.g., drug-induced, brain lesions or trauma)
• History of major psychiatric disorders (e.g., bipolar disorder, schizophrenia, obsessive-compulsive disorder)
• History of neurological diseases other than CD (e.g., epilepsy, Parkinson's disease)
• Other contraindications for TMS or brain MRI (e.g., metal in the head)
• Pregnant or breastfeeding women
• History of substance abuse or dependence