As reported by The Hartford Courant, March 23, 2004.

Getting Their Signals Straight

– 'Brain Pacemaker' Helps Parkinson's Patients Prevent Debilitating Lockup of Their Muscles

By William Hathaway

Parkinson's disease can lock up William Stanziano's muscles so quickly, he says it feels like a crowbar thrust into a gearbox.

"Sometimes I walk into a Dunkin' Donuts and can't walk out," said Stanziano, who may have to wait patiently for hours until medication kicks in and loosens his limbs enough to get home.

Four months ago, the 51-year-old Wolcott man went to the University of Connecticut Health Center, where doctors implanted a "brain pacemaker" - electrodes placed deep inside his brain that are designed to short-circuit the errant signals that can immobilize him.

The procedure, known as deep brain stimulation, is one of a growing number of promising treatments that use electricity to heal ailing minds.

For Stanziano, deep brain stimulation is designed to compensate for the death of brain cells that produce the neurotransmitter dopamine, essential for many muscle movements. The death of dopamine-producing cells is caused by Parkinson's disease.

Stanziano's medication had stopped preventing the muscular lockup that his doctors call the "off" state, a period when his muscles are not functioning. The advanced stage of his disease and his relative good health made Stanziano eligible to receive a brain pacemaker. People with milder forms of Parkinson's, dementia patients and those in ill health are not eligible for the procedure, which carries a slight risk of internal bleeding or infection.

After more than a decade of successful trials, deep brain stimulation has now entered the mainstream of Parkinson's treatment. Deep brain stimulation requires two separate operations - one to implant electrodes deep into the patient's brain, and a second to implant two hockey-puck-size pulse generators on both sides of the chest. A hand-held pulse programmer controls the high-frequency electrical signals, which in Stanziano's case are sent to each side of the subthalamus, an area of the brain involved in movement.

The hardware costs $25,000. The technology is similar to cardiac pacemakers, used to regulate the heart, and vagus nerve stimulation, used to control epilepsy.

Although deep brain stimulation has led to a few spectacular successes in unlocking the frozen gaits and ending the debilitating tremors of Parkinson's patients, it does not cure the disease, said Dr. J. Antonelle "Toni" de Marcaida, director of the movement disorders program at UConn.

"There is no real evidence that it is neuro-protective," she said.

And it doesn't work for everyone, although trials have shown eight of 10 Parkinson's patients do show improvement that lasts more than five years, de Marcaida said.

Stanziano also now realizes that deep brain stimulation does not work overnight. Doctors must tinker, sometimes for months, with the strength of the electric pulses and the dosages of dopamine-replacing medicine to get the best results. Although doctors can adjust the strength of the pulse with the hand-held programmer, patients can only turn the pulse generators on or off.

For Stanziano, the results have been mixed since he received his brain pacemaker last November. He no longer has the residual Parkinson's symptoms he used to have when he is in his "on," or more functional, state. However, when he is in the "off" state, his condition is as bad as before the operation, he said.

Doctors can't tell patients why the technology sometimes doesn't work, because they don't fully understand why it works at all.

Some researchers suggest electrical stimulation affects the release of specific neurotransmitters that compensate for the lack of dopamine, while others have argued that electrical pulses reset abnormal electrical signals in the brain.

Scientists still may not know why, but they have known for more than 70 years that modifying electrical impulses in the brain can have therapeutic benefits, said Dr. Sara H. Lisanby, associate professor of clinical psychiatry and medical director of Columbia University's depression center.

Deep brain stimulation is an indirect descendant of some of those early treatments, she said.

The earliest use, in electric shock therapy, has been condemned for the pain and such side effects as memory loss that it afflicted upon patients with mental illness. However, in the past two decades, scientists have rehabilitated the procedure, and today, targeted electrical convulsive therapy "remains the most effective treatment for depression, period," Lisanby said.

However, even carefully targeted applications of electricity still can cause memory loss, and scientists have been searching for ways to reduce the side effects. Lisanby's laboratory, for instance, is working with magnets as a safer way to alter electrical impulses and treat depression. The procedure is now in clinical trials.

Lisanby said magnets have not been shown to be effective in treating Parkinson's, which involves structures deeper in the brain.

Deep brain stimulation's ability to reach deep into the brain is why it also is being used as a treatment for obsessive-compulsive disorder. The symptoms of patients with obsessive-compulsive disorder seem to improve when electrodes are placed in an area of the brain near the basal ganglia - one of the brain areas also targeted in Parkinson's patients.