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.
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
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.
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.
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.
- INCLUSION CRITERIA:
To be eligible for entry into the study, candidates must meet all the following criteria:
1. Patients greater than 7 years of age with generalized primary dystonia.
2. Patients who are refractory to medical treatment (including levodopa,
anticholinergics, benzodiazepines, Baclofen) who are considered surgical candidates.
Patients will be determined to have medical refractory dystonia after having been
treated by at least two medications of two different groups at the maximum
recommended dose for a duration of at least two months.
3. In case of treatment by intrathecal Baclofen delivered by a pump, a change to oral
Baclofen must be performed, so that the pump can be taken out.
4. Patients must have a minimum BFM score of 20 on optimal medical therapy.
5. Adults must be mentally competent to consent for entrance into the protocol at the
time of admission.
6. Patients must have a signed DPA for research purposes.
Candidates will be excluded if:
1. The patient has had previous lesioning surgery including radiofrequency lesioning of
deep nuclei (thalamus, pallidum, STN).
2. The patient currently has a functioning and effective stimulator in deep brain nuclei
(thalamus, pallidum, STN).
3. The patient is not able to tolerate surgery, as determined by the preoperative
4. The patient has a coagulopathy demonstrated by an abnormal prothrombin time,
activated partial thromboplastin time, or thrombocytopenia (platelet count less than
5. The patient has an acute or untreated infection (viral, bacterial or fungal).
6. The patient has a contraindication to MR-imaging such as previous surgery that
involved placement of metal objects that could cause tissue damage or produce image
7. The patient has another chronic neurologic disorder.
8. The patient is pregnant at the time of surgery.
9. The patient has epilepsy.
10. The patient does not have access to proper follow-up care at home and may not be
eligible for the study.