Posted on Mon, Jul. 26, 2004

The body electric
Deep brain stimulation is effective for thousands with Parkinson's. One day, electricity may treat such varied ailments as obesity and depression.
By Stacey Burling
Inquirer Staff Writer

How's this for a bizarre, sci-fi scene?

Carman Wylie lies on an operating table at Temple University Hospital. Five metal pins are screwed into his balding head. A black plastic and metal contraption rises from a dime-sized hole above his right temple. To his right is a computer screen showing MRI pictures of his brain. To his left is another computer alight with an X-ray. It reveals a skinny metal wire probing into his subthalamic nucleus, home of the Parkinson's disease tremors that have made it impossible for the 64-year-old Muncy, Pa., man to sit or stand still.

Wylie's eyes are open. For hours, under local anesthesia, he has listened as neurosurgeon Jack Jallo drilled into his skull, as the OR team discussed how to put new equipment together, as a device that listens to electrical signals in his brain helped Jallo guide the wire through the cortex, the white matter and the thalamus. Wylie is getting jittery.

Jallo leans close. "This is where it's important to work with us," he says.

It's time to turn on the deep brain stimulator - four tiny electrodes at the end of the wire that will release 180 pulses of electricity per second. Wylie will help the OR team confirm it has found the right spot. Jallo asks Wylie to raise his arm and repeatedly touch his nose.

He's not shaking anymore. Wylie says his hand has not been so steady in years.

Jallo is satisfied and locks the stimulator in place.

Cutting-edge as it looks, deep brain stimulation for Parkinson's disease - approved by the FDA in 2002 and already in use in 25,000 people worldwide - is an older form of treatment in a new and rapidly expanding field called neuromodulation.

Researchers are exploring various ways of zapping parts of the brain with small amounts of electricity. The approach also is approved by the FDA for two other movement disorders, essential tremor and dystonia, and epilepsy. It is being tested for a host of other conditions: depression, obsessive-compulsive disorder, anxiety, obesity, bulimia, pain, migraine, stroke, and Alzheimer's, and even for patients who are in a minimally conscious state, a condition just a couple steps above coma. Experts believe electrical treatments also hold promise for attention-deficit/hyperactivity disorder, dyslexia, autism, Tourette's syndrome and schizophrenia.

The techniques capitalize on the growing recognition that the brain functions through electrical and chemical signals. Some neurosurgeons foresee a time when they will be less likely to cut into the brain with a scalpel. Instead, they'll deliver drugs, gene therapy, new cells, and corrective electrical stimulation directly to malfunctioning sections of the brain.

"I absolutely think this is the future," said Ashwini Sharan, a neurosurgeon at Thomas Jefferson University Hospital.

Doctors, who use these treatments only in patients who don't respond to anything else, don't really know what the electrical stimulation is doing. In some cases, it makes an area of the brain more active. But it may block signals or slow activity in others. Hence, the imprecise word "modulation."

Neuromodulation experts acknowledge that talk of psychiatric treatments that may alter or disable parts of the brain makes people uneasy. It quickly brings to mind some relatively recent and unsavory history - the widespread use of lobotomies and shock treatments.

But doctors say these new treatments are nothing like lobotomy, which permanently disconnected the frontal lobes from the rest of the brain, or even shock therapy, which still hasn't recovered from One Flew Over the Cuckoo's Nest. They are much more targeted, and the devices can always be turned off.

Joseph Fins, chief of the division of medical ethics at Weill Medical College of Cornell University, said the history had been distorted. Lobotomy, which was prevalent before the advent of antipsychotic drugs, was more helpful than many people believe, he said. Some hospitals continue to use surgery that removes much smaller parts of the brain for depression and obsessive-compulsive disorder (OCD).

Any discussion of the new treatments, Fins said, needs to keep in mind that severe depression or OCD can be as devastating as Parkinson's disease.

"We're sort of forgetting the burden of illness that people are feeling," he said.

Neuromodulation comes in three forms: deep brain stimulation; vagus nerve stimulation (VNS), in which an electrode is attached to the body's largest nerve at the neck and sends signals from there into a broad swath of the brain; and cortical stimulation, in which a paddle-shaped electrode is attached to the outside of the brain under the skull. All are powered by batteries implanted in the chest, just like those for heart pacemakers. In fact, doctors often think of the devices as brain pacemakers.

Deep brain stimulation is approved for treating Parkinson's and two other disabling movement disorders, dystonia and essential tremor.

The results can be dramatic. Jim Evridge, a Pennsville, N.J., man with Parkinson's, hasn't used his cane since his deep brain stimulator was turned on at Temple in April 2003. If he turns it off, he said, "within less than 30 seconds, I just become a quivering, trembling mass of muscle."

Doctors at Pennsylvania Hospital, which has an active program in deep brain stimulation, are part of a study of whether the technique can reduce epileptic seizures.

Ali Rezai, a Cleveland Clinic neurosurgeon who is active in neuromodulation research, said results of early tests of deep brain stimulation for OCD and depression were encouraging.

Cleveland Clinic and Cornell, he said, are also embarking on a clinical trial of deep brain stimulation for patients in a minimally conscious state after severe brain injury.

The device used in cortical stimulation has been approved for deployment on the spine but is used off-label in the brain. Jeffrey Brown, a Wayne State University neurosurgeon who is an expert on cortical stimulation, said it had been effective for treating chronic facial pain resulting from stroke or injuries. It is being studied for restoring movement in people disabled by a stroke. In the future, Brown said, it may be used for the chronic pain that sometimes occurs after a bout of shingles, for phantom limb pain, and for other types of nerve injury.

Doctors at the University of Pennsylvania were involved in creating a "smart" device being tested for epilepsy. It uses an implant in the brain that senses when a seizure is about to begin and tells a cortical stimulator to fire.

Vagus nerve stimulation, which was developed by a Temple physiologist, is the least invasive but also least precise of the approaches. It was approved by the FDA for treatment of epileptic seizures in 1997. An FDA advisory panel last month recommended that it also be approved for treating severe depression. Although not binding, such recommendations are usually accepted.

Charlie Donovan, a 45-year-old former Wall Street bond salesman who lives in St. Louis, suffered from depression so severe that he couldn't work and barely left his house. He had tried shock therapy and at least 10 antidepressants but still was in "utter despair."

Donovan tried vagus nerve stimulation in 2001 as part of a clinical trial and is so happy with the results that he testified in favor of VNS before the FDA. "I can experience genuine happiness and joy where in the past I had to fake it," he said. The only drawback, he said, was that the treatment initially caused hoarseness.

Richard Rudolph, chief medical officer for Cyberonics, a Houston company that makes the vagus nerve stimulator, said there was little evidence that it worked for anything other than epilepsy and depression. But, he and others familiar with the device said researchers had either done small studies or were considering them for Alzheimer's disease, severe headache, anxiety, OCD, post-traumatic stress disorder, heart rhythm problems, and obesity. The University of Minnesota recently began a study financed by the National Institutes of Health to find out whether the treatment can help stop vomiting in patients with bulimia nervosa, a condition characterized by repeated binge eating and vomiting. The treatment made news this summer when New Orleans surgeons used it to successfully treat a man who had suffered through seven months of constant, stroke-induced hiccups.

Several experts on neuromodulation said they doubted a single treatment could dramatically affect so many different conditions.

"It does not make physiological sense to have applications for all these different areas," Rezai said.

Robert Fisher, a Stanford University neurologist who wrote the American Academy of Neurology's guidelines for VNS in epilepsy, said there was reason for skepticism but also for hope. Doctors have learned the drugs that work for epilepsy also often work for depression, bipolar disorder and nerve pain. All are probably caused by neurons that are firing too rapidly, he said. An electrical treatment that affects those neurons might affect several diseases, Fisher said.

Contact staff writer Stacey Burling at 215-854-4944 or sburling@phillynews.com.