DOPAMINE AGONISTS INCREASE THE RISK OF VALVULAR REGURGITATION

25th August 2011 - New research

Movement Disorders [2011] 26 (5) : 801-806 (V.G.Rasmussen, K.Østergaard, E.Dupont, S.H.Poulsen) 

The use of dopamine agonists increases the risk of valvular regurgitation in people with Parkinson's Disease. Valvular regurgitation is when a cardiac valve becomes diseased or damaged, and is no longer able to close properly. Leakage of blood occurs across the valve.  This leakage of blood is referred to as regurgitation.  Valvular regurgitation can lead to abnormal cardiac function. For more information go to Mitral valvular regurgitation.

Cabergoline, which is also known by the brand names Dostinex and Cabaser, was the worst of those dopamine agonists assessed. The likelihood of valvular regurgitation in people with Parkinson's Disease taking Cabergoline was more than six times greater than would otherwise be expected.. The dopamine agonist Pergolide, which is also known as Permax, makes valvular regurgitation in people with Parkinson's Disease more than three times more likely. The likelihood of Permax causing valvular regurgitation led to its withdrawal in the U.S. in 2007, but it is still used elsewhere. Other dopamine agonists were not assessed. So it is not known to what extent they are harmful in this respect or if they are harmful at all.

What is Deep Brain Stimulation for Parkinson's Disease?

 

Deep brain stimulation (DBS) is a surgical procedure used to treat a variety of disabling neurological symptoms—most commonly the debilitating symptoms of Parkinson’s disease (PD), such as tremor, rigidity, stiffness, slowed movement, and walking problems.  The procedure is also used to treat essential tremor, a common neurological movement disorder.  At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications.

DBS uses a surgically implanted, battery-operated medical device called a neurostimulator—similar to a heart pacemaker and approximately the size of a stopwatch—to deliver electrical stimulation to targeted areas in the brain that control movement, blocking the abnormal nerve signals that cause tremor and PD symptoms. 

Before the procedure, a neurosurgeon uses magnetic resonance imaging (MRI) or computed tomography (CT) scanning to identify and locate the exact target within the brain where electrical nerve signals generate the PD symptoms.  Some surgeons may use microelectrode recording—which involves a small wire that monitors the activity of nerve cells in the target area—to more specifically identify the precise brain target that will be stimulated.  Generally, these targets are the thalamus, subthalamic nucleus, and globus pallidus.

The DBS system consists of three components:  the lead, the extension, and the neurostimulator.  The lead (also called an electrode)—a thin, insulated wire—is inserted through a small opening in the skull and implanted in the brain.  The tip of the electrode is positioned within the targeted brain area.

The extension is an insulated wire that is passed under the skin of the head, neck, and shoulder, connectng the lead to the neurostimulator.  The neurostimulator (the "battery pack") is the third component and is usually implanted under the skin near the collarbone.  In some cases it may be implanted lower in the chest or under the skin over the abdomen.

Once the system is in place, electrical impulses are sent from the neurostimulator up along the extension wire and the lead and into the brain.  These impulses interfere with and block the electrical signals that cause PD symptoms.

Is there any treatment?

What is the prognosis?

What research is being done?

The NINDS supports research on DBS to determine its safety, reliability, and effectiveness as a treatment for PD.  Currently, NINDS-supported scientists are trying to determine the site(s) in the brain where DBS surgery will be most effective in reducing PD symptoms.  These researchers are also comparing DBS to other PD therapies to find out which is more effective.

Although most patients still need to take medication after undergoing DBS, many patients experience considerable reduction of their PD symptoms and are able to greatly reduce their medications.  The amount of reduction varies from patient to patient but can be considerably reduced in most patients.  The reduction in dose of medication leads to a significant improvement in side effects such as dyskinesias (involuntary movements caused by long-term use of levodopa).  In some cases, the stimulation itself can suppress dyskinesias without a reduction in medication.

Unlike previous surgeries for PD, DBS does not damage healthy brain tissue by destroying nerve cells.  Instead the procedure blocks electrical signals from targeted areas in the brain.  Thus, if newer, more promising treatments develop in the future, the DBS procedure can be reversed.  Also, stimulation from the neurostimulator is easily adjustable—without further surgery—if the patient’s condition changes.  Some people describe the stimulator adjustments as "programming."

9th August 2011; THE LONG TERM EFFECTS OF DBS ON PARKINSON'S DISEASE

Archives of Neurology [2011] Published online August 8 (A.Castrioto, A.M.Lozano, Yu-Yan Poon, A.E.Lang, M.Fallis, E.Moro) 

Researchers assessed the outcome of Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) in people with Parkinson's Disease over a period of 10 years. Deep Brain Stimulation (DBS) involves the use of electrodes that are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS requires careful programming of the stimulator device in order to work correctly. DBS improved the Parkinson's Disease symptom score by 25% in comparison to no treatment, including resting and action tremor by over 85%, and bradykinesia by 23%. It did not stop deterioration in speech, walking, and postural instability, including falling and freezing. L-dopa dosages reduced to about 63% of what they were initially. Daily living activity also improved. Dyskinesia and motor fluctuation scores also remained significantly lower. Potential adverse events included : a trend to weight loss, visual hallucinations, impulse control disorders possibly related to dopamine agonists, progressive cognitive decline culminating in dementia,  device related infections.

Nicotine Protects Against Parkinson’s?

Northwest Parkinson's Foundation:

The addictive component of cigarettes saves dopamine neurons from a Parkinson’s-like decline, providing a new avenue for potential treatment.Jef Akst

The Scientist - Nicotine protects the brain against the loss of dopamine neurons, a characteristic sign of Parkinson’s disease, according to a study published this week in The FASEB Journal.

By activating the alpha-7 nicotinic receptor, nicotine—which increases dopamine levels in the brain—appears to be able to rescue mouse dopaminergic neurons cultured under conditions that favor their loss. Genetically engineered mouse cells that lacked a specific nicotine receptor (the alpha-7 subtype), however, were unaffected by nicotine treatment.

The findings suggest that new Parkinson’s therapies may be developed to target nicotine receptors, FierceBiotech reports. “This study raises the hope for a possible neuroprotective treatment,” said co-author Patrick P. Michel of the Institut du Cerveau et de la Moelle Épinière, Hôpital de la Salpêtrière, in Paris, France, in a statement.

But this is not an endorsement for cigarettes, FASEB noted. “If you’re a smoker, don’t get too excited,” Gerald Weissmann, editor-in-chief of The FASEB Journal, said in a statement. “Even if smoking protects you from Parkinson’s, you might not live long enough to develop the disease because smoking greatly increases the risk for deadly cancers and cardiovascular diseases.”

Sleep Disorder is Risk Factor for Parkinson’s

From the Northwest Parkinson's Foundation: Rick Nauert PhD

Psych Central - A new European study suggests individuals suffering from REM sleep behavior disorders have an increased risk of developing Parkinson’s disease (PD).

REM sleep behavior disorders are characterized by dream nightmares in which a person is attacked and pursued leading an individual to scream, cry, punch and kick while sleeping.

The current study is the third work on the topic within the last five years to be published by Lancet Neurology.

The first work showed in 2006 that 45 percent of patients who suffer this sleep disorder develop Parkinson’s disease and other neurodegenerative diseases caused by a lack of dopamine in the brain.

The second article discovered that neuroimaging tests that measure dopamine in the brain, such as the brain SPECT scan (single-photon emission computed tomography), are useful to identify patients with REM sleep disorders with increased risk of developing a neurodegenerative diseases such as Parkinson’s disease.

In the current study, researchers used SPECT to conclude that the levels of dopamine in the brain are quickly lowering over the years in patients with REM sleep behavior disorder.

SPECT is the first neuroimaging technique to detect the disease progression at an early stage. The study involved comparing for three years the evolution of brain SPECT in 20 patients with REM disorder and 20 healthy controls.

The neuroimaging technique measures the presence of dopamine in the substantia nigra, a part of the brain associated with learning and harmony of body movements. In Parkinson’s disease, a deficiency of dopamine in the substantia nigra causes tremor, stiffness and movement slowness in patients.

Results showed that after three years of monitoring the production of dopamine in the control group was reduced by 8 percent due to age, while the group of REM sleep disorder patients experienced a reduction of 20 percent.

Once the three-year follow-up ended, three of 20 patients in the REM sleep disorder group had developed Parkinson’s disease and their dopamine reduction was around 30 percent.

Researchers conclude that more efforts are needed to create neuroprotective drugs that prevent the progression from REM sleep behavior disorders to Parkinson’s disease.

Authors of the study suggest that, to be considered effective, a neuroprotective drug should significantly prevent the dopamine concentration from dropping in these patients.

THE WORLD'S STRANGEST CAUSE OF PARKINSON'S DISEASE

31st July 2011 - New review

The world's strangest cause of Parkinson's Disease occurs in the western Pacific Ocean, amongst the Chamorro people. The Chamorro live in the Mariana islands, which includes the U.S. territory of Guam. The symptoms of Parkinson's Disease occur alongside ALS and dementia. It is thought that the Chamorro people develop the symptoms by eating a species of Flying Fox called the Mariana Fruit Bat. The Mariana Fruit Bats consume large quantities of neurotoxic cycad seeds. As the number of Mariana Fruit Bats has declined so has the illness.

Eating these bats is a centuries old tradition amongst the Chamorro people. The Chamorro consider it a culinary delicacy. Served at weddings, fiestas, and birthdays, the etiquette of bat-eating and preparation involves rinsing off the outside of the animal like you would a cucumber and then tossing it in to boiling water. The bats are then served whole in coconut milk and are consumed in their entirety. Meat, internal organs, fur, eyes, and wing membranes are all eaten.

Increased risk of Parkinson’s disease in methamphetamine users, CAMH study finds

For Immediate Release - July 26, 2011- (Toronto) - People who abused methamphetamine or other amphetamine-like stimulants were more likely to develop Parkinson’s disease than those who did not, in a new study from the Centre for Addiction and Mental Health (CAMH).

The researchers examined almost 300,000 hospital records from California covering 16 years. Patients admitted to hospital for methamphetamine or amphetamine-use disorders had a 76 per cent higher risk of developing Parkinson’s disease compared to those with no diagnosis.

Globally, methamphetamine and similar stimulants are the second most commonly used class of illicit drugs.

“This study provides evidence of this association for the first time, even though it has been suspected for 30 years,” said lead researcher Dr. Russell Callaghan, a scientist with CAMH. Parkinson’s disease is caused by a deficiency in the brain’s ability to produce a chemical called dopamine. Because animal studies have shown that methamphetamine damages dopamine-producing areas in the brain, scientists have worried that the same might happen in humans.

It has been a challenge to establish this link, because Parkinson’s disease develops in middle and old age, and it is necessary to track a large number of people with methamphetamine addiction over a long time span.

The CAMH team took an innovative approach by examining hospital records from California – a state in which methamphetamine use is prevalent – from 1990 up to 2005. In total, 40,472 people, at least 30 years of age, had been hospitalized due to a methamphetamine- or amphetamine-use disorder during this period.

These patients were compared to two groups: 207,831 people admitted for appendicitis with no diagnosis of any type of addiction, and 35,335 diagnosed with cocaine use disorders. A diagnosis of Parkinson’s disease was identified from hospital records or death certificates. Only the methamphetamine group had an increased risk of developing Parkinson’s disease.

While the appendicitis group served as a comparison to the general population, the cocaine group was selected for two reasons. Because cocaine is another type of stimulant that affects dopamine, this group could be used to determine whether the risk was specific to methamphetamine stimulants. Cocaine users also served as a control group to account for the health effects or lifestyle factors associated with dependence on an illicit drug.

“It is important for the public to know that our findings do not apply to patients who take amphetamines for medical purposes, such as attention deficit hyperactivity disorder (ADHD), since these patients use much lower doses of amphetamines than those taken by patients in our study,” said Dr. Stephen Kish, a CAMH scientist and co-author.

To put the study findings into numbers, if 10,000 people with methamphetamine dependence were followed over 10 years, 21 would develop Parkinson’s, compared with 12 people out of 10,000 from the general population. “It is also possible that our findings may underestimate the risk because in California, methamphetamine users may have had less access to health-care insurance and consequently to medical care,” said Dr. Callaghan.

The current project is significant because it is one of the few studies examining the long-term association between methamphetamine use and the development of a major brain disorder. “Given that methamphetamine and other amphetamine stimulants are the second most widely used illicit drugs in the world, the current study will help us anticipate the full long-term medical consequences of such problematic drug use,” said Dr. Callaghan.

Media Contact: Michael Torres, Media Relations, CAMH; 416-595-6015

The Centre for Addiction and Mental Health (CAMH) is Canada's largest mental health and addiction teaching hospital, as well as one of the world's leading research centres in the area of addiction and mental health. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental health and addiction issues. CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre.

RHINORRHEA IN PARKINSON'S DISEASE

26th July 2011 - New research

Movement Disorders [2011] 26 (2) : 320-323 (Chou KL, Koeppe RA, Bohnen NI.)

Rhinorrhea is nasal discharge, commonly referred to as a runny nose. For more information go to Rhinorrhea. Although, nasal discharge is usually assumed to occur for a variety of reasons such as colds, flu or allergies, it is a common symptom in Parkinson's Disease. Researchers have found that people with Parkinson's Disease multiplied the likelihood of nasal discharge 5 times the average. This is after other possible causes had been accounted for.
Over two thirds (68%) of people who had Parkinson's Disease reported nasal discharge. There was no relationship with age or severity of symptoms. The nasal discharge of over half (52%) of people with Parkinson's Disease was accompanied with light headedness. The symptom of lightheadedness is uncommon in people who do not have Parkinson's Disease, occurring in less than 1 in 10. Another recent study found similar results.  The frequency of nasal discharge can lead to a reduction in the sense of smell, which is common in Parkinson's Disease.

It is not clearly known what causes this relationship. Nasal discharge occurring so frequently in Parkinson's Disease is not directly due to low dopamine, and a previous study found no relationship between rhinorrhea and dopamine agonists.

Single and dual task gait training in people with Parkinson's Disease: A protocol for a randomised controlled trial

From Northwest  Parkinsons Foundation:      

 

Difficulty performing more than one task at a time (dual tasking) is a common and disabling problem experienced by people with Parkinson disease (PD). If asked to perform another task when walking, people with PD often take shorter steps or walk more slowly.

Currently there is uncertainty about whether clinicians should teach people with PD to avoid dual tasking or whether they should encourage them to practice dual tasking with the hope that practice will lead to enhanced performance. This study will address this issue by comparing single to dual task gait training.Methods and design: A prospective randomised clinical trial is being conducted.

Sixty participants with idiopathic PD will be recruited, provided they score I-IV on the modified Hoehn and Yahr (1967) scale, and fulfil other inclusion criteria. Participants will be randomly allocated to either a single or dual task gait training group.Both groups will receive 12 hours of walking training over 4 weeks. The single task group will undertake gait training with cueing strategies to increase step length.The dual task group will train to improve step length when walking and performing a variety of added tasks.

Both groups will receive a tailored home program for 6 months.Blinded assessors will conduct four assessments: two baseline assessments, one post intervention and one at 6 months follow-up.

The primary outcome measure will be step length when dual tasking over 8m.Secondary outcome measures include: spatiotemporal gait parameters when walking under single and dual task conditions, measures of executive function, the timed up and go test, measures of community mobility, and quality of life.

All analyses will be based on intention to treat principle. Discussion. This trial will examine the immediate and longer term effect of dual task walking training as compared to single task training in people with idiopathic PD, at the impairment, activity, and participation levels.

It has the potential to identify a new intervention that may improve and maintain walking beyond the laboratory. The results of this trial will provide guidance forclinicians in the development of walking training programs for people with PD.Trial Registration: ACTRN12609000791235

PARKINSON'S DISEASE FOUNDATION FUNDS ELEVEN NEW PROJECTS

11th July 2011 - News release

The Parkinson’s Disease Foundation has announced awards totalling more than $1 million for 11 novel research projects, which they claim are "designed to understand the cause(s) of and find a cure for Parkinson’s disease." The research ranges from basic science investigations to studies of potential new therapies and symptomatic relief.

The primary cause of Parkinson's Disease is the insufficient formation of dopamine in the dopaminergic neurons, which are the brain cells specialised in producing dopamine. Yet most of the projects are quite remote from this basic biochemistry of Parkinson's Disease. One of them aims at studying "the role of norepinephrine" and "the potential of norepinephrine-targeted therapies to treat" Parkinson's Disease. However, norepinephrine is not produced by the cells affected in Parkinson's Disease, and the formation or lack of formation of norepinephrine has never been shown to cause Parkinson's Disease. Another project is to assess "the role of the mitochondria in Parkinson’s" Disease using "Transparent Zebrafish". The mitochondria is the energy producing part of all brain cells. It is not directly involved in dopamine formation, and its deficiency has never been shown to cause Parkinson's Disease. Another project concerns the "Identification of Genes for Parkinson's Disease in an Isolated Greek Community". However, genetic mutations have only ever been proven to make Parkinson's Disease more likely in a small number of people. Other studies include looking at the use of "Electrical Stimulation", "Identification of Neuroprotective Factors in Tobacco", generating "interest in Parkinson’s research and patient care among basic scientists and clinicians", and "Small Aromatic Molecules as Novel Inhibitors of Alpha-Synuclein Aggregation".