AO is a 25-year-old female with primary generalized dystonia. The first symptom she noticed was a turning inward of her left foot while walking at 4 years of age. Testing at that time, including an MRI of the brain and blood work, was normal. Her father had carried the diagnosis of generalized dystonia from a young age, so it was suspected early on that she might also have the same condition. Eventually, both she and her father were discovered to have a mutation in the DYT1 gene, which regulates the production of torsin A protein and is responsible for most cases of early-onset primary dystonia.
AO's symptoms remained mild until 7 years of age, when she developed more difficulty holding a pencil and drawing and was diagnosed with writer's cramp. In junior high, she had more difficulty writing and began typing reports and exams on a laptop. At age 20, she developed increasing left-leg dystonia and involuntary toe flexing. The more she walked, the more severe the dystonia affected the left leg.
Initially, AO was very active and could run and participate in sports without trouble, but she gradually noticed more difficulty walking long distances or running. She also experienced cramping and abnormal posturing in her arms and back with certain activities. Sometimes she also had a mild tremor in her arms, especially under stressful conditions.
In the past, AO had tried medications, including Sinemet (carbidopa-levodopa) to rule out the rare possibility of dopamine-responsive dystonia (with no effect), clonazepam (which caused cognitive side effects) and Artane (trihexyphenidyl). For one and a half years before referral to UCSF, she had taken 2 mg of Artane in the morning, which had minimal effect on her dystonia. Higher doses caused severe dry mouth. She had been treated with Botox injections in her toe flexors and upper legs every three months in an attempt to improve her walking, with very minimal benefit.
As a patient with severe primary generalized dystonia who had unsatisfactory results from traditional medical therapies and had continued, significant disability, AO was referred to the UCSF Movement Disorders Program. When AO came to UCSF, she was entering her third year of law school, working at an internship. A multidisciplinary team of movement disorders specialists — neurologist Jill Ostrem, M.D., stereotactic neurosurgeon Philip Starr, M.D., Ph.D., and colleagues — evaluated her. A careful history and neurological exam were performed, including a videotaped exam of her dystonia and determination of the severity of her dystonia with standardized dystonia rating scales.
It was determined that AO was an excellent candidate for treatment with deep brain stimulation (DBS) therapy because she had failed medical therapy, suffered from significant disability from her dystonia, was in excellent physical health aside from her dystonia, had a known cause of dystonia (DYT1 mutation) that historically responds very well to DBS therapy, had not developed any fixed orthopedic deformities and was well informed with realistic expectations and commitment to follow-up after surgery.
DBS surgery was performed by Starr, who has extensive experience with such surgeries. During surgery, AO was lightly sedated and two small burr holes were drilled into the skull. She was then awakened from sedation before a microelectrode was inserted into the left globus pallidus. Intraoperative testing was done to confirm correct electrode placement. A Medtronic DBS electrode was inserted into this location, tested, and then implanted in the left side of the brain.
After successful retesting, the scalp was closed and the patient was put under general anesthesia, so that subcutaneous extension wires could be placed down the neck. A generator/control unit was then placed in AO's chest wall under her right clavicle.
Since surgery, AO has traveled to UCSF on several occasions for adjustments in her DBS programming for active, maximal dystonia control. At her last follow-up visit, she was noted to have a 60 percent improvement in her symptoms. The most noticeable improvement in dystonia has been in her left leg, which no longer shows any signs of dystonia.
She no longer has difficulty walking long distances, is an avid kickboxer and has also noticed better control of her arm and hand movements. She has been able to discontinue taking Artane. AO recently graduated from law school, took the bar examination and is currently enjoying international travel before joining a law practice in San Francisco.
For more information, call Jill Ostrem, M.D., at (415) 353-2273 or Phillip Starr, M.D., at (415) 353-7500.
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