Insights Into Deep Brain Stimulation (DBS) for Cervical Dystonia
Condition: Cervical Dystonia
MeSH terms: Dystonia; Dystonic Disorders; Torticollis
Study type: Observational

Summary: 
      The purpose of this research study is to determine the physical brain changes in people with
      cervical dystonia after deep brain stimulation (DBS) surgery and as compared to healthy
      controls. We will do this by measuring your body's response to transcranial magnetic
      stimulation (TMS) before and/or after DBS surgery.

      TMS is a non-invasive procedure during which you sit in a chair that looks like one you would
      find at the dentist's office. A nerve stimulator is placed on the wrist of the right hand to
      stimulate the median nerve; the intensity of the nerve stimulator is gradually increased
      until the right thumb begins to twitch. A magnetic coil is placed on the scalp on one side of
      the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles
      in the opposite hand.

      If you are a control subject, and therefore will not/have not have DBS surgery, we will
      measure the body's response to TMS for comparison purposes. We expect that the electrical
      differences in the brain may be related to the physical benefits some patients with primary
      cervical dystonia receive from DBS surgery.
    

Detailed description: 
      Subjects will participate in 1-3 visits, based on eligibility, as described below:

      Study Visit 1: Baseline

        -  This visit applies to subjects with cervical dystonia who are planning DBS surgery in
           the next 1-4 weeks

        -  This visit applies to subjects with cervical dystonia who are not planning DBS surgery

        -  This visit (except #3) applies to healthy control subjects; this is the only visit for
           healthy control subjects

             1. A neurological examination with special attention to the sensory system will be
                performed. The sensory system is the system by which the brain receives and
                perceives feelings from different parts of the body.

             2. Women of child-bearing potential will be given a urine pregnancy test to evaluate
                pregnancy status.

             3. DYSTONIA SUBJECTS ONLY: Clinical assessment of dystonia will be performed by
                administering several scales and measures, including: the Toronto Western Cervical
                Dystonia Rating Scale (TWSTRS), the Short Form (SF-36) scale for quality of life
                assessment, Visual Analog Scale (VAS) for assessment of dystonia and pain severity,
                the Mini Mental Status Examination (MMSE) for cognitive testing, and the Beck
                Depression Inventory (BDI II), for evaluation of mood.

             4. We will determine your individual motor evoked potential (MEP) threshold before
                beginning the study treatment. Your MEP will be recorded from a muscle located
                between the right thumb and index finger on your right hand, and then on your left
                hand. MEP threshold refers to the amount of stimulation to the brain that is
                required to activate muscle cells enough to appear on an electromyography (EMG),
                which records electrical potential in muscle through electrodes placed on the skin.

             5. We will test your sensory system and its interaction with the motor cortex by using
                transcranial magnetic Stimulation (TMS). For these tests, you will sit in a chair
                that looks like one you would find at the dentist's office. A nerve stimulator will
                be placed at the wrist of your right hand to stimulate the median and ulnar nerves.
                The intensity of the nerve stimulator will be gradually increased until the right
                thumb begins to twitch. A magnetic coil will be placed on the scalp on the left
                side of your head, overlying the brain's motor cortex, to stimulate the brain's
                output to the muscles in the opposite hand. This procedure will be repeated using
                the left wrist and the right side of your head.

             6. We will spend an additional 30 minutes performing a protocol that allows for
                testing of plasticity changes in the brain. This protocol is called paired
                associative stimulation (PAS). The median nerve in your wrist and the TMS coil over
                your head undergo repeated paired stimulation. Such repeated pairing builds
                plasticity effect in the motor cortex. MEP, as explained earlier, is recorded
                before and after this protocol.

             7. Subjects who have provided consent will be videotaped during this visit.

      Study Visit 2:

        -  This visit will be identical to Visit 1 for subjects with cervical dystonia who are not
           planning DBS

        -  This visit, as described below, applies to subjects with cervical dystonia who have had
           DBS less than 3 months prior

             1. This study visit involves 2 conditions and will be performed approximately 3 months
                after DBS surgery over a span of up to 3 days. For each condition your DBS
                stimulator will be kept either ON or OFF.

             2. A physical examination, including the clinical dystonia rating scales and TMS tests
                used during Visit 1, will be administered and recorded for both conditions.

             3. PAS, as described above for Visit 1, will be performed both ON and OFF stimulation
                to test the plasticity effects of DBS surgery.

             4. Additionally, women of childbearing potential will be given a urine pregnancy test
                to evaluate pregnancy status.

             5. Subjects who have provided consent will be videotaped.

      Visit 3:

        -  This visit applies to subjects who have had DBS surgery 6 months or more prior

             1. The method and plan will be identical to that used during Visit 2.
    

Intervention name(s): Transcranial magnetic stimulation (TMS)
Intervention type(s): Procedure
Intervention description(s): We will test the sensory system and its interaction with the motor cortex by using TMS. For these tests, you will sit in a chair that looks like one you would find at the dentist's office. A nerve stimulator will be placed on the wrist of your right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of your head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of your head.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be recruited from the University of Florida Center for Movement Disorders &
        Neurorestoration out-patient population, patient care meetings, the UFMDC research
        database, and during the course of normal clinical care. Additionally, we plan to enroll
        subjects from other DBS centers. Patients who are diagnosed with primary (or predominantly
        primary) cervical dystonia and are candidates for DBS surgery, or who have already had DBS
        surgery, will be identified as candidates for this research study.

        Control subjects will be recruited via advertising flyers in the local community.
      
Keywords: Deep Brain Stimulation; DBS; Transcranial Magnetic Stimulation; TMS; Cervical Dystonia; Dystonia; Control; Healthy