Booster Shots

Oddities, musings and news from the health world

Category: Parkinson's

Deep brain stimulation for Parkinson's works equally well at two sites, researchers say

June 2, 2010 |  3:30 pm

In a surprising finding, researchers have discovered that deep brain stimulation for Parkinson's disease is equally effective at either of the two most commonly used sites. Parkinson experts had believed that stimulation of the subthalamic nucleus was more effective than stimulation of the globus pallidus interna for controlling movement symptoms, but that it was more likely to aggravate other symptoms of the disease. But a new study of 299 patients randomized to receive one or the other of the techniques concluded that there were only very minor differences between the approaches. The study was reported Wednesday in the New England Journal of Medicine.

Parkinson's, which strikes as many as 100,000 Americans each year, is characterized by muscle control problems that produce shaking, rigidity, slowed movement and poor balance. Patients also tend to develop mental problems, including depression, apathy, slowed thinking, confusion, impaired memory and trouble sleeping. The disorder is caused by the loss of brain cells that produce the neurotransmitter dopamine, which plays a key role in transmitting commands from the brain to muscles. Its cause is unknown, but is at least partially genetic.Medtronic DBS 2 Leads

Medications such as L-dopa can control motor symptoms initially, but over time, they can worsen some symptoms. Researchers have also attempted to implant fetal brain cells to replace the dopamine-producing cells and have attempted gene therapy for the same purpose, but the results of such tests remain problematic. Perhaps the best intervention when medications begin to fail is deep brain stimulation, in which a surgeon threads a fine electrode through the brain to either the subthalamic nucleus or the globus pallidus, both of which are involved in motor control. The electrodes, one on each side of the head, are connected to a battery implanted in the chest that produces a minute electrical stimulation of the brain cells. Surgeons often see an improvement in patients while they are still on the operating table.

The new study is actually the second phase of a major clinical trial. In the first phase, deep brain stimulation in the patients at 13 U.S. centers was compared with the best treatment with medications and physical therapy. Researchers reported last year that stimulation was more effective at controlling all the symptoms. At the end of that stage, the patients who had been receiving drugs were randomized to receive deep brain stimulation.

"We found that motor outcomes between the two groups were not significantly different," Dr. Kenneth Follett of the University of Nebraska Medical Center, one of the lead authors, said in a statement. "Meanwhile there were very modest differences in mood and cognitive function between the two groups. Patients and physicians can have confidence in both types of [deep brain stimulation], and can make their choice based on the constellation of motor and nonmotor symptoms that determine the quality of life in Parkinson's disease."

On possible difference between the two approaches is that targeting the subthalamic nucleus allowed doctors to reduce the patient's dose of L-dopa by a larger amount. For patients who need higher levels of L-dopa to control nonmotor symptoms, targeting the globus pallidus might be a better choice, they said.

The study was funded primarily by the Department of Veterans Affairs and the National Institute of Neurological Diseases and Stroke. Some funding was provided by Medtronic Inc. of Minneapolis, which manufactures the equipment used.

-- Thomas H. Maugh II

Illustration: In deep brain stimulation, a battery and electronics implanted in the chest provide a minute electrical stimulus to the brain through implanted electrodes. Credit: Medtronic

Parkinson's meds and compulsive behaviors: a strong link

May 10, 2010 |  1:00 pm

Here's a perplexing medical irony: For Parkinson's disease patients, initiating certain voluntary movements such as walking and rising from a chair can be difficult. But the medications that help ease the challenging motor symptoms of Parkinson's seem to make it harder for some patients to halt certain behaviors that can be rewarding or pleasurable -- gambling, buying, eating, sexual stimulation.

While physicians have known about the link between Parkinson's medication and compulsive gambling since about 2005, little was known about how many patients are affected this way, whether the compulsive behavior went beyond gambling for some, and whether this is clearly a medication-induced problem. A study in the Archives of Neurology released Monday answers those questions.

Some 13.6% of Parkinson's Disease patients taking levodopa or one of the dopamine-agonist medications widely used for the movement disorder show clear signs of some impulse-control disorder. That rate was between 2 and 3.3 times higher among Parkinson's patients being treated with these medications than among patients who did not take them. About a quarter of those patients suffered from more than one type of compulsive behavior.

Compulsive buying was the most common manifestation of such impulse-control problems, affecting 5.9% of all medicated patients; 5% experienced problem or pathological gambling;  4.3% engaged in binge eating behaviors; and 3.5% engaged in compulsive sexual behavior.

Compulsive buying and binge eating were more common among women patients than among men; compulsive sexual behavior afflicted more men than women. The researchers also found some evidence that genetic inheritance might make some patients more vulnerable to these side effects of Parkinson's disease medicine: Patients were far more likely to develop compulsive buying, eating or gambling behaviors if they had a first-degree relative with a known gambling problem.

Finally, the study, which included 3,090 Parkinson's disease patients, found that those taking a combination of levodopa and one of the other dopamine-agonist medications (including pramipexole and ropinirole) were most likely to develop an impulse-control disorder; those on a dopamine agonist without levodopa were slightly less likely to develop such behavioral problems; and those on levodopa alone were about half as likely as the first two groups to develop impulse-control problems.

Researchers are gleaning insights into why and how some people become addicted to substances or behaviors from the experiences of Parkinson's patients. Here's a terrific overview of the curious link between Parkinson's medications and compulsion.

But you don't need to be a Parkinson's patient to have a compulsive behavior problem. Have a look here if gambling is your weakness; here if you compulsively seek out sexual stimulation; here if you buy or shop compulsively; and here if you think you might have a binge-eating problem.

-- Melissa Healy

Industrial solvent linked to increased risk of Parkinson's disease

February 7, 2010 |  4:13 pm

Exposure to the industrial solvent trichloroethylene increases a person's risk of developing Parkinson's disease nearly sixfold, California researchers said Sunday. Animal studies had suggested a potential problem with the solvent, but the new study by Dr. Samuel Goldman of the Parkinson's Institute in Sunnyvale is the first to quantify the risk.

Parkinson's disease, caused by the death of cells in the brain that secrete the neurotransmitter dopamine, is characterized by severe tremors, rigidity in the limbs and other symptoms. It strikes an estimated 100,000 Americans each year and is ultimately fatal. Genetics play a role in susceptibility to Parkinson's, but it has also been linked to head trauma, pesticides and illicit drugs.

Trichloroethylene, or TCE, is a solvent that was once widely used in dry cleaning and to clean grease off metal parts, and it was once used as an anesthetic, especially during childbirth. But concerns about its toxicity led to it being mostly abandoned and replaced by other anesthetics and solvents. There have been at least three reports of clusters of Parkinson's among workers exposed to TCE. Animal experiments following those reports showed that the chemical kills dopamine-producing cells in substantia nigra, the part of the brain affected in Parkinson's disease. It also impairs mitochondria -- the power sources of brain and other cells -- in the same locations that are affected by the illicit chemical MTPT, which is known to cause Parkinson's. "There's a lot of circumstantial evidence to show that it is relevant," Goldman said in an interview.

Goldman and his colleagues identified 99 sets of twins from the World War II Veteran Twins Cohort in which one twin had Parkinson's and the other didn't. They collected job histories for each subject and then had them analyzed blindly by an industrial hygienist and a preventive medicine specialist to assess exposure to occupational chemicals.

Goldman and his team found that exposure to the chemicals xylene, toluene and n-hexane was not associated with an increased risk of Parkinson's. Those exposed to TCE, however, were 5.5 times as likely to develop the disease as those who were not exposed. Those exposed to either TCE or tetrachloroethylene, known as PERC, had eight times the risk. Those exposed to carbon tetrachloride had 2.8 times the risk, and those exposed to PERC had nine times the risk; in both cases, however, the results fell short of statistical significance.

"Part of the problem is that the usage of the substances overlaps quite a bit," he said. Nonetheless, the "very high odds ratio" for TCE "is impressive, and certainly mandates that large population-based studies follow this up." Goldman will report his findings at a Toronto meeting of the American Academy of Neurology in April.

Those who were exposed to TCE had job histories primarily as dry cleaners, machinists, mechanics or electricians. Because the exposure estimates were not precise, Goldman said, the study needs to be replicated. To begin with, the team is looking at larger databases, and they will most likely try to find cohorts of people with high exposure to the chemicals to see how many have Parkinson's. "I think people will really move on this as quickly as possible now," he concluded.

-- Thomas H. Maugh II

A new portrait of the where -- and the who -- of Parkinson's disease

January 28, 2010 |  9:44 am

Mapping cases of Parkinson's disease, the second-most common neurodegenerative disease behind Alzheimer's, might prove illuminating. We could see where the progressive condition is more common and maybe get some potential research leads.

Scientists at Washington University in St. Louis have done this. Using data on Medicare recipients, they've learned that the Northeast and the Midwest have significantly more cases of the disease, and that whites and Latinos are more likely to develop it than are blacks and Asians.

Here are the very brief abstract for the study, published in Neuroepidemiology, and the news release (complete with the aforementioned and enlightening map). The lead author suspects a connection to environmental risk factors, specifically to chemicals used in agriculture and metal processing.

For a primer on Parkinson's disease, there's this overview from the National Parkinson Foundation. It begins:

Parkinson's disease (PD) was first described in 1817 by Dr. James Parkinson, a British physician, for whom the disease was named. It is a disease that is characterized by four major features:

-- Rest tremor of a limb (shaking with the limb at rest).
-- Slowness of movement (bradykinesia).
-- Rigidity (stiffness, increased resistance to passive movement) of the limbs or trunk.
-- Poor balance (postural instability).

-- Tami Dennis  

Gaucher disease linked to Parkinson's

October 21, 2009 |  5:04 pm

People who carry the gene for a rare genetic problem known as Gaucher disease have at least five times the normal risk of developing Parkinson's disease, researchers reported today in the New England Journal of Medicine. Some clinicians had noticed an apparent link between the two conditions in the past, but a new international study of nearly 5,700 people is the first to show the magnitude of the risk. The finding suggests that the gene is one cause of the disease, but indicates that other factors must be operating as well because not all patients who have Gaucher also develop Parkinson's.

Gaucher disease, which afflicts an estimated 5,400 Americans, is caused by defects in the gene known as GBA, which serves as the blueprint for the production of an enzyme known as glucocerebrosidase. The enzyme breaks down a fatty substance called glucocerebroside which, when not disposed of, can harm the spleen, liver, lungs, bone marrow and, in some cases, the brain. People with two defective genes suffer from the disease, which comes in three distinct types. Lifespan may range from as little as 2 years to as many as 40 or 50.

People with only one defective gene do not suffer from symptoms and are said to be carriers. About one in 100 Americans carries the gene, but among certain groups, like Ashkenazi Jews, the incidence rises to one in 15. It was previously thought that the gene was harmless in such people, but the new results show that is not the case.

Dr. Ellen Sidransky of the National Human Genome Research Institute had been intrigued by an observed link between Gaucher and Parkinson's. To explore it, she organized a consortium of 64 researchers at 16 institutions worldwide--virtually every Gaucher researcher in the world. They studied two common GBA variants in 5,691 people with Parkinson's disease, including 780 Ashkenazi Jews, and compared them to 4,898 disease-free individuals, including 387 Ashkenazi Jews.

They found that 3.2% of the Parkinson's patients had at least one of the common variants, compared with only 0.6% of the healthy people, a five-fold increase. Among the Jews, 15.3% of those with Parkinson's carried the gene, compared with 3.4% of healthy Jews.

Five of the research centers sequenced the entire GBA gene in 1,642 non-Ashkenazi Parkinson's patients and 609 health non-Ashenazis, looking for other mutations. They found mutant genes in 7% of the patients, indicating that their risk of developing Parkinson's was 10 times normal.

The finding does not offer any new ideas about how to treat Parkinson's disease. Indeed, researchers are currently at a loss to explain the mechanism by which the defective gene increases the risk of Parkinsonism, which affects an estimated 3 million to 4 million Americans. But they hope that exploring the link will provide new information about how the disease develops and progresses.

-- Thomas H. Maugh II

Perhaps the first drug to slow progression of Parkinson's disease

September 23, 2009 |  3:29 pm

Using a new kind of clinical trial, researchers may have discovered the first drug that can actually delay the progression of Parkinson's disease, a disabling and ultimately fatal neurological disorder. Several drugs are available that can mitigate the symptoms of Parkinson's, but that very easing of the symptoms makes it extremely difficult to tell whether the drug is having any permanent effect on the disease itself. To get around that problem, Dr. C. Warren Olanow of the Mount Sinai School of Medicine in New York and his colleagues used an unusual clinical trial design called a delayed-start trial. The idea of the trial is to start two groups of patients on a drug at different times. If the drug is actually delaying the progression of the disease, then the group that gets it later should not receive as great a benefit as those who received it first.


Olanow and his colleagues at 129 medical centers in 14 countries studied 1,176 patients with early Parkinson's disease who had not been given other forms of therapy. Half the patients were given the drug rasagiline (sold under the brand name Azilect by Teva Pharmaceutical Industries of Israel) and half a placebo. After nine months, the group that had been given placebo was also given rasagiline, while those who had received it initially continued to receive it. The progression of their disease was measured on the widely used Unified Parkinson's Disease Rating Scale, which ranges from zero to 176 and includes subscales of mental function, activities of daily living and motor events. Higher scores indicate more severe disease.

The team reported today in the New England Journal of Medicine that patients given a 1-milligram dose of the drug for the entire 18 months of the study showed less worsening of the disease in the first nine months. Their symptoms were improved as much as those in the second group during the second nine months of the study. In short, they were better off at the end of 18 months than the patients who had received Azilect for only nine months, suggesting that the drug had delayed the course of the disease. "If this can be confirmed, this would be the first drug determined to have a disease-modifying effect in Parkinson's disease, and that is exciting news for the PD community," Olanow said.

But Olanow noted a complication of the study: Those who received a 2-milligram dose of the drug were, overall, no better after 18 months than those who had received the higher dose for only nine months. He speculated that the reduction of symptoms from the higher dose made it difficult to observe any effects on disease progression. This possibility was supported by the observation in a small group with the most serious symptoms that they did do better after 18 months, but it will require further study.

Parkinson's disease affects more than 1 million Americans and is characterized by impaired motor skills including tremor, stiffness and slowness of movement. The symptoms worsen as the disease progresses. The most common treatment is the drug levo-dopa, which replenishes a neurotransmitter that is lost in the course of the disease. Because Azilect has few side effects and only modest benefit for symptoms, Olanow suggested that it would be best to use it early in the course of the disease and save other drugs for when symptoms worsen.

The study was funded by Teva, which was responsible for data collection, monitoring and statistical analysis. Olanow reported receiving consulting and lecture fees from the company.

-- Thomas H. Maugh II

Photo: Pope John Paul II was one of the many victims of Parkinson's disease. Credit: Vincenzo Pinto / AFP


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