Transcranial Magnetic Stimulation for Children With Tourette's Syndrome
Condition: Tourette Syndrome
MeSH terms: Tourette Syndrome; Syndrome
Study type: Interventional

Summary: 
      Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary
      movements or sounds. In some children, these tics can be especially bad and require
      treatment, however, options are limited. It is only with time and practice that youth with
      Tourette syndrome are better able to suppress their tics. For these reasons, new
      interventions are needed. The investigators will target a brain region involved in tics
      called the supplementary motor area. Using low frequency repetitive transcranial magnetic
      stimulation, the investigators will inhibit the activity, in a similar way to the tic
      suppression that develops with age. The investigators propose the following objectives: (Aim
      1) The investigators hypothesize that Tourette syndrome symptom severity (as measured by the
      Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial
      magnetic stimulation targeting the supplementary motor area. (Aim 2) The investigators
      further hypothesize that improvement in Tourette syndrome symptoms will be moderated by low
      frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate
      in the supplementary motor area, and changes in the functional connectivity between the
      supplementary motor area and primary motor cortex. Eleven children (7-12 years of age) with
      Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation
      (five times a week for three weeks). After the three weeks, they will look for changes in tic
      severity and brain chemistry and function. By developing a novel avenue for treating Tourette
      syndrome, they can directly impact the care of children by reducing the severity of tics and
      improving quality of life.
    

Detailed description: 
      Background Tourette syndrome is very common. It affects over 80,000 Canadian youth. Tics are
      the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements
      or sounds. In some children, these tics can be especially bad and require treatment, however,
      options are limited. Medications for Tourette syndrome carry significant risk of side
      effects. Behavioral treatments, like habit reversal therapy, show promise and are safe, but
      are difficult to apply to younger children. It is only with time and practice that youth with
      Tourette syndrome are better able to suppress their tics. Finally, neither medication nor
      behavior therapies directly target the root cause of the tics. For these reasons, new
      interventions are needed.

      Specific Objectives The investigators will target a key brain region involved in tics. It is
      called the supplementary motor area. Using low frequency repetitive transcranial magnetic
      stimulation, they will inhibit the activity of that brain region, in a similar way to the tic
      suppression that develops with age.

      The investigators propose the following specific objectives:

      (Aim 1) The investigators will characterize the effect of low frequency repetitive
      transcranial magnetic stimulation of the supplementary motor area on Tourette syndrome
      symptoms. They hypothesize that Tourette syndrome symptom severity (as measured by the Yale
      Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic
      stimulation targeting the supplementary motor area.

      (Aim 2) The investigators will identify the changes in brain metabolites (glutamate and GABA)
      and functional connectivity caused by low frequency repetitive transcranial magnetic
      stimulation that normalize brain activity. They hypothesize that improvement in Tourette
      syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic
      stimulation induced changes in GABA and glutamate in the supplementary motor area. This will
      be assessed with proton magnetic resonance spectroscopy, potentiation of GABAergic
      neurotransmission assessed with short-interval cortical inhibition, and changes in the
      functional connectivity between the supplementary motor area and primary motor cortex.

      Methods Eleven children (7-12 years of age) with Tourette syndrome will be undergo low
      frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks). The
      investigators will assess the key variables with interviews and brain imaging of the children
      before and after the three-week intervention. After the three weeks, they will look for
      changes in tic severity and brain chemistry and function.

      Expected Results The investigators have pioneered transcranial magnetic stimulation
      applications in child and adolescent populations. By developing a novel avenue for treating
      Tourette syndrome, they can directly impact the care of children by reducing the severity of
      tics and improving quality of life.
    

Intervention name(s): Low frequency repetitive transcranial magnetic stimulation
Intervention type(s): Device
Intervention description(s): Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tourette Syndrome; Children; Tics