Deep Brain Stimulation for Cervical Dystonia
Condition: Dystonia; Generalized Primary Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will evaluate the effectiveness of deep brain stimulation (DBS) in treating
      primary generalized dystonia. Patients with dystonia have muscle spasms that cause
      uncontrolled twisting and repetitive movement or abnormal postures. Medical therapies are
      available, but not all patients get adequate relief from the abnormal movements or the pain
      associated with them. DBS is a surgical procedure that interrupts neuronal circuits in the
      Gpi and STN, areas of the basal ganglia of the brain that do not work correctly in patients
      with dystonia. The surgery results in decreased movement and therefore may lessen patients'
      symptoms and pain.

      Patients 7 years of age and older with generalized dystonia that does not respond to medical
      treatment may be eligible for this study. Candidates are screened with blood and urine tests,
      chest x-ray, and an electrocardiogram in patients 35 years of age or more.

      Participants undergo the following tests and procedures:

        -  Magnetic resonance imaging. MRI uses a magnetic field and radio waves to produce images
           of the brain. The patient lies on a table that is moved into the scanner (a narrow
           cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur
           during the scanning process. The procedure usually lasts about 45 to 90 minutes, during
           which the patient is asked to lie still for up to 15 minutes at a time.

        -  Transcranial magnetic stimulation. This procedure maps brain function. A wire coil is
           held on the scalp, and a brief electrical current is passed through the coil, creating a
           magnetic pulse that stimulates the brain. During the stimulation, the patient may be
           asked to tense certain muscles slightly or perform other simple actions. The stimulation
           may cause a twitch in muscles of the face, arm, or leg, and the patient may hear a click
           and feel a pulling sensation on the skin under the coil. During the stimulation,
           electrical activity of muscles is recorded with a computer, using electrodes attached to
           the skin with tape.

        -  Neurologic evaluation. Before and after DBS, the patient's dystonia, including voice
           strength and difficulty swallowing, are measured with a standardized rating scale.

        -  DBS treatment. Patients are randomly assigned to have electrodes implanted in either the
           Gpi or STN area of the basal ganglia. The electrodes are what stimulate the brain in DBS
           therapy. Before surgery, a frame is secured to the patient's head, and an MRI scan is
           done. DBS involves making two small incisions and two small holes in the skull, opening
           the lining around the brain, locating the Gpi or STN, securing the electrodes in place
           and connecting them to the pulse generator that is placed under the skin below the
           collar bone. Additionally, during the surgery, the patient is asked to move certain
           muscles. The muscle activity is recorded to gain a better understanding of the
           physiology of movement. After surgery, computed tomography (CT) and MRI scans are done
           to confirm placement of the electrodes.

        -  Stimulation and evaluation. After surgery, patients' movements are evaluated during and
           after stimulation. The changes in movement and function are videotaped and scored
           according to a rating scale. The optimal stimulation settings are determined and the
           stimulators are adjusted accordingly.

        -  Follow-up. Patients are evaluated, with videotaping, at 1, 2, 3, 6, 12, 18 and 24 months
           after surgery, and the stimulators are adjusted as needed.
    

Detailed description: 
      OBJECTIVE:

      For dystonic patients who have failed medical therapy, stereotactic deep brain stimulation
      (DBS) of the globus pallidus interna (Gpi) or subthalamic nucleus (STN) can provide
      significant symptom improvement, but it is not known which site provides maximum benefit or
      the physiologic mechanisms by which these improvements may occur. The study goals are to
      determine if DBS of Gpi or STN provides significant clinical improvement in patients with
      primary generalized dystonia, whether the anatomic DBS site (if either) provides optimal
      improvement, and to gain deeper insight into the underlying pathophysiology of this disorder.

      STUDY POPULATION:

      Adult and pediatric patients with medically refractory primary generalized dystonia will
      make-up the study population. Patients with primary generalized dystonia suffer a wide range
      of symptoms including physical deformity, speech difficulties, swallowing dysfunction, visual
      problems, and intractable pain, which can result in an inability to care for themselves.
      Moreover, pediatric primary generalized dystonia patients will often have abnormal skeletal
      development (scoliosis) resulting from the abnormal forces placed on the skeleton by dystonic
      muscle contractions.

      DESIGN:

      We propose placing DBS electrodes (using microelectrode guidance) bilaterally into either the
      Gpi or STN of medically refractory dystonia patients. Physiological studies will be performed
      and compared with clinical changes to understand the mechanism of action of DBS and
      underlying pathophysiology of dystonia.

      OUTCOME MEASURES:

      Clinical effectiveness of DBS of the Gpi or STN will be measured by the Burke-Fahn-Marsden
      Scale (BFM) and monitored over time to determine the effectiveness of DBS and if there is an
      ideal anatomic stimulation site. Electrophysiologic outcome measures will be obtained to
      determine the underlying pathophysiology of dystonia, and the mechanism of action of DBS.
    

Intervention name(s): Deep Brain Stimulation
Intervention type(s): Procedure
Primary purpose: Treatment
Keywords: Surgery; Treatment; Physiology; Pediatric; Neurosurgery; Generalized Primary Dystonia