Brain Damage in Parkinson’s May Be Less Severe

Damage to the brains of victims of Parkinson’s disease, when symptoms are first detected, may not be as severe as physicians had once thought, researchers said here Wednesday.

The damage is confined to the brain’s putamen, which controls muscle functions, said neurologist E. Stephen Garnett of Chedoke-McMaster Hospitals in Hamilton, Canada. The damage does not extend into the caudate nucleus, which is involved in thought processes, as scientists had believed on the basis of autopsies, he said at the Third Chemical Congress of North America.

The finding could lead to improved success rates for brain graft surgery, a new technique that has been used with certain Parkinson’s victims.

Garnett for the first time applied an imaging technique called positron emission tomography to study biochemical activity in the brains of Parkinson’s victims.

Parkinson’s disease, which is characterized by tremors and rigidity of the limbs, affects an estimated 1.5 million people in the United States, most of them over the age of 55. About 30% of Parkinson’s victims also develop dementia, an impairment of thought processes.

No one knows what causes Parkinson’s, but its symptoms are caused by a deficiency of dopamine, a hormone that carries messages in the brain. The disease is usually treated with L-dopa, a drug that is converted to dopamine in the brain.

In the last year, between 150 and 200 victims worldwide have been treated with an experimental--and controversial--operation in which dopamine-secreting tissues from the adrenal gland are transplanted into the brain.

The new research reported here suggests that the brain graft surgery could be improved by placing the grafted tissue near the putamen instead of near the caudate, as is now done, Garnett said.

Related research also shows that, in at least one brain graft recipient, the operation produced improvement in brain function at caudate and putamen cells on the opposite side of the brain, said chemist Alfred P. Wolf of the Brookhaven National Laboratory in Upton, N.Y. This finding suggests, he said, that the operation may stimulate recovery of some damaged brain cells.

The positron scanning is based on the use of short-lived radioisotopes that decay by emitting positrons, electrons with a positive charge, which pass through the body and are recorded by radiation detectors. The radioisotopes are attached to chemicals that are used in the brain or other parts of the body and are then injected into the body. The scanning then reveals how much of the chemical is found at each site in the brain.

In the most widespread application, the radioisotope fluorine-18 is attached to sugar molecules that the brain uses for energy. By mapping the location of the labeled molecules, the scans show which parts of the brain are working the hardest at any particular time.

Garnett has built a special high-resolution scanner that enables his group to visualize very small areas of the brain, and thereby distinguish between emissions from the putamen and the caudate.

About five years ago, Garnett and his colleagues developed a form of L-dopa that may be attached to fluorine-18. They have since used it to monitor biochemical activity in the brains of more than 200 Parkinson’s victims.

“To our surprise, all the scans showed significant damage only to the putamen,” and little or no damage to the caudate, Garnett said.

Studies of healthy individuals showed that the biochemical activity of the putamen declines slowly with age, he said. His evidence suggests that the Parkinson’s victim receives damage to many nerve cells in the putamen about 15 to 20 years before the onset of the disease. Symptoms of the disease become apparent only when the continuing deterioration brings the percentage of damaged nerve cells in the putamen up to 80%, he said.

“This (time lag) is going to make it very hard to discover the cause of Parkinson’s,” he noted.

Researchers have so far studied only a handful of Parkinson’s patients who have received brain grafts. Garnett has studied one such patient, who did not improve after the surgery.

Wolf has studied four such patients. Three of them showed no improvement, and he also observed no change in dopamine activity. The fourth did improve, and he observed an increased use of dopamine in the patient’s brain. Interestingly, the increase was on the opposite side of the brain from where the cells were implanted.

This result supports the growing idea that the transplant is stimulating regeneration of brain cells rather than simply serving as a dopamine source, Wolf said.

Both Garnett and Wolf are confident that the scanning will help explain whether and how the surgery works, “But we’ve still got much too small a patient sample to start drawing any conclusions,” Wolf said.