While there are commonly known medical treatments for Parkinson's disease, the dwindling efficacy of these treatments over time often drives both patients and physicians to seek promising new treatments. This was the case in May 2007 when, after 13 years of medical treatment, a 55-year-old male was referred to the multidisciplinary Center for the Surgical Treatment of Movement Disorders at UCSF.
The patient's history revealed that carbidopa-levodopa and eventually a dopamine agonist had for many years effectively addressed his symptoms of tremor, bradykinesia and rigidity. Yet by 2005, symptom control was weakening and the patient had developed disabling motor fluctuations, dyskinesia and painful left foot toe curling.
In response, his referring neurologist added a COMT inhibitor and an MAO-B inhibitor to the other Parkinson's medications. When these didn't achieve enough symptom improvement, the neurologist increased the dopamine agonist dosage and the frequency of the carbidopa-levodopa. This improved the patient's motor symptoms, but contributed to his developing hallucinations and delusions that were severe enough to require psychiatric hospitalization.
The referring neurologist then discontinued the dopamine agonist and placed the patient on an atypical neuroleptic. This improved the psychiatric symptoms, but the Parkinson's disease motor symptoms worsened.
Neurologist Jill Ostrem, M.D., who saw the patient the morning he arrived at UCSF Medical Center, says, "Our observation was that the patient had been properly treated medically, but with the complications there were few other medication strategies available." After a complete neurological examination, Ostrem felt the man was a good candidate for deep brain stimulation (DBS). She then briefed neurosurgeon Philip Starr, M.D., Ph.D., who met with the patient the same day.
In June 2007, Starr performed bilateral DBS in the subthalamic nucleus. He also placed an implantable pulse generator in the patient's chest wall. The patient went home after a few days, returning a week later to have his sutures removed and battery activated.
"We then saw him every month for the next four months to adjust both his DBS settings and his medications," Ostrem says. "At his last appointment with us in January 2008, his symptoms were greatly improved, with minimal motor fluctuations and no dyskinesia. Though he was still experiencing intermittent left foot dragging, occasional toe curling and a little rigidity, overall he was very happy with the symptomatic treatment."
At that point, the patient returned to his referring movement disorder neurologist, who is comfortable in adjusting medications and monitoring the DBS stimulator. "We continue to be available, though, should the referring neurologist or the patient need us," Ostrem says.
The case highlights how an academic medical center can bring advanced treatment options for neurological disorders into the clinical setting. Another example is a phase I trial recently completed by the UCSF Movement Disorders Clinic and Rush University. The trial uses a gene therapy approach to treat Parkinson's disease.
"Using a viral vector, patients with advanced Parkinson's disease had a gene inserted into the striatum. The gene expresses a protein called neurturin, a growth factor," Ostrem says. "The hope is that by increasing the production of neurturin in this part of the brain, we might be able to slow or reverse the neurodegenerative aspect of Parkinson's disease by helping the dying neurons fight back and survive."
Ostrem and her colleagues Starr, William Marks, M.D., Graham Glass, M.D., and Paul Larson, M.D., are participating in a multicenter, randomized, sham-surgery control phase II trial to further understand the possible benefit of this approach.
For more information, contact Dr. Ostrem at (415) 353-2311 or Dr. Starr at (415) 353-3489.
DBS surgery may be appropriate when the following is indicated in a patient:
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