Joining Forces to Discover Causes of Dystonia

Ueli Rutishauser, PhD 
Adam Mamelak, MD 
Michele Tagliati, MD

Three Cedars-Sinai researchers are combining forces to probe the causes of dystonia, a movement disorder with no known cure that can cause crippling muscle contractions. Funded by a $75,000 grant from the Gustavus and Louise Pfeiffer Research Foundation awarded July 1, they hope their study will contribute to improving current treatment regimens or suggest new strategies.

The co-investigators are Ueli Rutishauser, PhD, assistant professor of neurosurgery; Adam Mamelak, MD, professor of neurosurgery, and Michele Tagliati, MD, professor of neurology and director of the Movement Disorders Program in the Department of Neurology.

In most cases of dystonia, the cause is unknown. The study's hypothesis is that dystonia is a learning disorder in which the motor cortex shows abnormally high levels of change, or "plasticity." Other areas of the brain that control movement – the basal ganglia – then overcompensate by producing abnormal levels of activity. This process results in the excessive, involuntary muscle contractions that typify the disorder, Rutishauser suggested.

To test this hypothesis, investigators will record neural activity while patients undergo awake brain surgery to implant devices for deep brain stimulation (DBS), a treatment technique that stimulates an abnormally active part of the brain with electrical current. DBS often is effective in relieving symptoms of both dystonia and Parkinson's disease, a progressive neurological disorder with symptoms such as tremors, rigidity, slowness of movement and impaired balance.

During the surgery, the patients will be asked to engage in learning tasks, such as moving a joystick to trace an image on a computer screen, that require them to associate a motor action with visual stimuli. As the patient performs the task, investigators, using microelectrodes, will record activity in the motor cortex and reactions of individual neurons in the basal ganglia to monitor how these areas interact.

The pilot study will enroll up to 20 patients in two groups: those diagnosed with dystonia and a control group diagnosed with Parkinson's disease. By studying differences in brain activity between these two groups, the investigators hope to identify a unique pattern in dystonia patients.

"One of the puzzling observations that prompted this study is that the effect of DBS is almost immediate in treating tremor in Parkinson's disease, but it may take weeks or months to show effectiveness in dystonia patients," Rutishauser said. He said he suspects that the underlying neuronal mechanisms by which DBS suppresses symptoms are different in the two disorders.

Ultimately, Rutishauser hopes, the team's research may help to more precisely target deep brain stimulation or even inspire alternative treatments for dystonia. It may be possible one day to help patients "unlearn" abnormal brain plasticity through behavioral therapy, reducing their symptoms, he suggested.