For many years, researchers have known that the movement problems associated with Parkinson's disease result from a loss of neurons that produce a nerve-signaling chemical called dopamine in one part of the brain. A new study suggests that Parkinson's disease (PD) also affects nerve endings that produce a related chemical, norepinephrine, in the heart. The finding improves understanding about how Parkinson's disease develops and may lead to a way of predicting the disorder and possibly even preventing it.
The study also improves understanding of orthostatic hypotension, or a fall in blood pressure when a person stands up, which is a common complication of Parkinson's disease. This condition can cause dizziness, lightheadedness, and fainting.
Using positron emission tomography (PET) scans, researchers at the National Institute of Neurological Disorders and Stroke (NINDS) found that nearly all of the 29 Parkinson's disease patients they studied had decreased numbers of norepinephrine-producing nerve endings in the heart. This finding suggests that Parkinson's is more than just a brain disease and may be caused by an abnormality that affects the peripheral nervous system, which includes the sympathetic nervous system, as well as the brain. The study, and a related editorial, appear in the September 5, 2000, edition of the Annals of Internal Medicine.(1) (2)
The loss of nerve terminals in the heart was not related to whether the patients had taken the drug levodopa, which is converted to dopamine and is commonly prescribed to treat Parkinson's patients, says David S. Goldstein, M.D., Ph.D., Chief of the Clinical Neurocardiology Section at NINDS, who led the study. The extent of loss was also unrelated to the duration or severity of the disease.
Loss of norepinephrine-producing nerves throughout the heart was found in the nine Parkinson's patients who also had orthostatic hypotension. However, most of the Parkinson's disease patients without orthostatic hypotension also had evidence of decreased sympathetic nerve terminals in the heart. The sympathetic nervous system controls blood pressure, pulse rate, perspiration, and many other automatic responses to stress. Since norepinephrine and dopamine are part of the same family of chemicals, called catecholamines, the new finding suggests that whatever causes the loss of dopamine-producing nerve terminals in the brain also causes the loss of sympathetic nerve terminals in the heart.
The number of sympathetic nerve terminals was normal in patients with multiple system atrophy (MSA), a disorder which often resembles Parkinson's disease and is characterized by severe orthostatic hypotension. Checking for loss of sympathetic nerve terminals in the heart might therefore help physicians distinguish between Parkinson's disease and multiple system atrophy. This is particularly important because some drugs that act on the sympathetic nervous system including non-prescription herbal remedies-can cause dangerous rises in blood pressure in patients with MSA whose sympathetic nerves are intact, says Dr. Goldstein.
While other recent imaging studies have suggested that sympathetic nerves in the heart are lost in Parkinson's disease, the new study used sophisticated tests to confirm that the imaging findings were due to the loss of sympathetic nerve terminals and that this loss causes the orthostatic hypotension in Parkinson's patients. These tests included measurements of norepinephrine in the blood coming from the heart and of blood pressure responses to the Valsalva maneuver, in which patients blow into a tube, producing temporary decreases in the amount of blood pumped by the heart. People with a fully functioning sympathetic nervous system are able to compensate for the decrease in blood output by the heart because the brain responds by directing an increase in traffic in sympathetic nerves. This constricts blood vessels, "like tightening the nozzle at the end of a garden hose," allowing the blood pressure to return to normal, says Dr. Goldstein. If the sympathetic nervous system is damaged, however, this tightening does not occur, and blood pressure decreases progressively, causing orthostatic hypotension.
Dr. Goldstein and his colleagues are now carrying out studies to determine if the loss of sympathetic nerve terminals is restricted to the heart or if it also affects other organs of the body. They also hope to determine why dopamine- and norepinephrine-producing nerve terminals in the heart and in only a particular part of the brain are lost in Parkinson's disease. According to what Dr. Goldstein calls the "getaway car hypothesis," the sympathetic nervous system in the heart is always working in case the body suddenly needs to escape. A toxin in the blood could cause the nerve terminals to wear out prematurely, just as a toxin in the fuel line of a car can corrode the engine after months of idling. A related hypothesis which Dr. Goldstein calls the "catalytic converter hypothesis" is that a toxic breakdown product builds up in dopamine- and norepinephrine-producing nerves due to lack of a necessary enzyme in those nerves. The "getaway car hypothesis" might explain not only why Parkinson's patients have a loss of sympathetic nerve terminals in the heart but also why they have a loss of dopamine-producing neurons in the brain, which may point to a way of predicting and ultimately preventing the disorder.
(1) Goldstein, David S., Holmes, Courtney, Li, Sheng-Ting, Bruce, Simon, Metman, Leo Verhagen, and Cannon, Richard, O III.
"Cardiac Synpathetic Denervation in Parkinson's Disease." Annals of Internal Medicine, Vol. 133, No. 5, September 5, 2000, pp. 338-347.
(2) Kaufman, Horacio. "Primary Autonomic Failure: Three Clinical Presentations of One Disease?" Annals of Internal Medicine, Vol. 133, No. 5, September 5, 2000, pp. 382-384.