Watch: The Connection Between Sleep Disorders and Parkinson's Disease

The Michael J. Fox Foundation for Parkinson's Research

4 hrs · 

Since your Parkinson's diagnosis, have you had difficulties sleeping? 

Watch: The Connection Between Sleep Disorders and Parkinson's Disease

Tips on getting a better night's sleep.

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DO MICROBES RULE YOUR BRAIN?

Do Microbes Rule Your Brain on Food Choices?

People no longer have to blame their food cravings — and giving in to them — on poor self-control.

Now scientists are arguing that microbes living in the gut are responsible for manipulating eating behavior by causing cravings for food they favor for fitness or that suppress their competition. Alternatively, microbiota in the gut may send out signals via the vagus nerve to the brain to induce dysphoria and goad people into eating what the microbe needs whether it’s good for the host or not, a diverse group of researchers are suggesting.

“Bacteria within the gut are manipulative,” Carlo Maley, PhD, director, Center for Evolution and Cancer, University of California at San Francisco, states in a press release. “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals and others not.”

In their overview of eating behavior and the microbiome published online August 7, 2014 inBioEssays, Joe Alcock, MD, University of New Mexico, Albuquerque, and colleagues argue that certain microbes are highly dependent on the nutrient composition of the diet.

For example, Prevotella grows best on carbohydrates while dietary fiber provides a competitive advantage to Bifidobacteria. “Even microbes with a generalist strategy tend to do better on some combinations of nutrients than others,” the authors write, “and competition will determine which microbes survive.”

Microbes can manipulate host behavior in a variety of ways, but one way may be by “hijacking” the host’s nervous system. As the authors point out, evidence shows that microbes can have dramatic effects on behavior through the microbiome-gut-brain axis.

“The vagus nerve is a central actor in this communication axis, connecting the 100 million neurons in the enteric nervous system in the gut to the base of the brain at the medulla,” they explain. And, they add, enteric nerves have receptors that react to the presence of particular bacteria as well as to bacterial metabolites. Research has also shown that blockade or transection of the vagus nerve causes drastic weight loss while stimulation of its activity through norepinephrine appears to drive excessive eating behavior in satiated rats.

Other pathways through which microbes may influence host eating behavior is through secretion of hormones involved in mood and behavior, including dopamine and serotonin. Microbes may also manipulate eating behavior by altering receptor expression. Changes in taste receptor expression and activity have been reported following gastric bypass surgery, a procedure that changes gut microbiota and alters satiety and food preference, as the authors point out.

“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad and releasing chemical rewards to make us feel good,” coauthor Athena Aktipis, PhD, Arizona State University, Phoenix, states in a press release.

“Together, these results suggest that microbes have opportunities to manipulate vagus nerve traffic in order to control host eating. Exerting self-control over eating choices may be partly a matter of suppressing microbial signals that originate in the gut.”

Happily, researcher add, the use of prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes can rapidly alter the microbiome within 24 hours of administration.

The study was funded by the National Institutes of Health, the American Cancer Society, the Bonnie D. Addario Lung Cancer Foundation, and the Institute for Advanced study in Berlin, Germany. The authors have disclosed no relevant financial relationships.

BioEssays. Published online August 7, 2014. Abstract

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Mapping the Placebo Effect to Speed Research

FoxFeed Blog

Posted by  Maggie McGuire, September 04, 2014

Many clinical trials require a placebo comparison to evaluate the effect of a new drug or therapy. Some people get the active intervention and some get an inactive “fake” treatment that looks the same as the real thing. Usually the volunteers don’t know if they’ve gotten the drug or the placebo.

Why can’t researchers just test the active agent? If you’re told you are receiving a drug that should make you better, you’ll probably start to feel better, even if the drug isn’t working. By giving some people the placebo and some the drug (but without them knowing which they’ve gotten), researchers can test to see if the people who got the drug have a better response.

Some of those people who got the placebo will report feeling better, too. Even if they don’t know they got the drug, their body reacts to the hope that it was the real thing. What causes this so-called “placebo effect?”

David Eidelberg, MD, director of the Center for Neurosciences at The Feinstein Institute for Medical Research a member of The Michael J. Fox Foundation Scientific Advisory Board, set out to answer that question. He talked to us about his recently published research into mapping response to sham (placebo) surgery and how his findings may help research move faster.

MJFF: First, why is the placebo effect a bad thing?

Dr. David Eidelberg: Some patients may think anything that makes them better is a good thing, but the placebo effect is unpredictable and unsustainable. It’s not a practical treatment strategy.

For research, it’s a big problem because you compare the placebo case with the idea that the control is supposed to be neutral. When there’s a significant change in the people who don’t have the drug, you’re not comparing to neutral. From a statistical aspect, it makes it more difficult, and you need more subjects to show you had a response with the drug.

And people who get the real therapy can have a placebo response, too. They’re not mutually exclusive. Maybe the clinical benefit is really multi-factorial. This issue of how much response is placebo and how much is surgical in one person is a deep problem.

Interestingly, the placebo effect is related to strength. If you’re testing a surgical intervention, the placebo effect will be stronger because you know the risk and the benefit will be higher. Your body will want it to be real. If you take a pill, you don’t think the risk is as high, so the effect won’t be as high. If you made it twice as likely that people get the drug (2/3 of volunteers get the drug and 1/3 get the placebo), the effect is greater because subjects think they have greater chance of getting the real thing.

MJFF: How did your study approach this problem?

DE: We used data from a study of PD patients who, rather than deep brain stimulation (DBS), opted for a clinical trial of a molecular approach to normalize brain activity.

So we used PET imaging to look at the brains of these subjects prior to sham surgery and again, six and 12 months afterward. Sixteen of 23 placebo volunteers had a response. We compared their scans and found a circuit (brain network) that was activated in responders (but not in non-responders) to sham surgery.

And the prospective subject score — an index of how active the network was at baseline — correlated to how well the patients did after the sham surgery. The more they improved (measured with the UPRDS), the more active the network was.

MJFF: How could researchers use this information?

DE: We found, too, that at baseline (before surgery) the hyper-responders had lower activity in that identified network. People who didn’t respond to sham surgery were already using that network beforehand. When you’re not using it and there’s more to access, you’re able to marshal those brain areas and produce a placebo response.

If one were to routinely screen for this network activity as part of research design, it may be possible to limit the number of sham surgeries needed to detect a valid treatment effect. By using imaging criteria to weed out potential hyper-responders, we produce a smaller, less variable control group, which improves the overall efficacy of the study. This approach also allows one to determine in those undergoing actual treatment the proportion of benefit attributed to the intervention versus placebo effect.

MJFF: What do you think predisposes someone to be a responder vs. a non-responder?

DE: No one knows, but it’s going to be a growth industry to find out. This network has presumably been present since birth, so it may have nothing to do with Parkinson’s. Maybe its expression is under genetic control.

The Ashkenazi Jewish Genetic Connection to Parkinson’s Disease

SEPTEMBER 4, 2014

Guest

By The Michael J. Fox Foundation for Parkinson’s Research

Do you know anyone who has Parkinson’s disease (PD)? It’s likely – the neurodegenerative disease affects one in 100 people over the age of 60, and more than 5 million people worldwide. Today, medicines exist to alleviate motor symptoms of the disease, but currently there are no treatments that can slow or stop its progression.

Researchers believe Parkinson’s results from a combination of both genetic and environmental factors, and, in recent years, scientists have discovered a number of genetic mutations associated with Parkinson’s. In about one percent of PD cases, the disease can be linked to a mutation in a gene called LRRK2.

While that may sound like a small number, the percentage is much higher in certain populations. In the Ashkenazi Jewish population, the mutation is responsible for 15 to 20 percent of PD cases. It is important to note that not everyone with a LRRK2 mutation will go on to develop Parkinson’s. But researchers believe that learning more about the genetics of Parkinson’s by studying those with and without the disease can help drive progress toward new treatments for everyone with PD.

A global study called the Parkinson’s Progression Markers Initiative (PPMI) launched efforts earlier this year to learn more about the genetics of PD. Families that carry a LRRK2 mutation have a vital role to play in this study, and there’s an easy way to be involved. The study is seeking volunteers to complete a brief survey to determine if they may be eligible to receive genetic counseling and testing of the LRRK2 gene at no cost. PPMI is looking for the following people to participate in the study:

• People with Parkinson’s disease who are of Ashkenazi Jewish ancestry
• People who do not have Parkinson’s but are related to someone who does have PDAND who are of Ashkenazi Jewish ancestry

Over the past decade, studies of the genetics of Parkinson’s disease have revolutionized the pursuit of a therapy that can slow or stop the progression of PD. Studying people with Parkinson’s and their families is essential to help researchers identify genetic traits that may contribute to PD. Taking the PPMI genetics survey or sharing it with family and friends makes you a critical partner in this mission. Visit michaeljfox.org/ppmi/genetics to get started today.

The Michael J. Fox Foundation for Parkinson’s Research, founded in 2000 by actor Michael J. Fox,  is dedicated to finding a cure for Parkinson’s disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson’s today. 

Northera (Droxidopa) for low blood pressure and dizziness in Parkinson's disease.

We were pleased to see the announcement on the availability of Northera (Droxidopa) for low blood pressure and dizziness in Parkinson's disease. In its approval, the FDA highlighted the fact that dizziness upon standing that can occur in people with Parkinson’s disease and is an unmet need and may contribute to falling and fractures.

If you, in consultation with your doctor, believe you may benefit from this drug, it will be available only through specialty pharmacies and your doctor will it have to complete a special form to prescribe it. Please call NPF's Helpline, 1-800-4PD-INFO for more information or visit http://www.drugs.com/northera.html.

Northera Information from Drugs.com

Northera (droxidopa) is used to treat neurogenic orthostatic hypotension. Includes Northera side effects, interactions and indications. DRUGS.COM

FDA Approves NortheraThe U.S. Food and Drug Administration (FDA) has granted accelerated approval of Northera (droxidopa) for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension (NOH), a rare, chronic and often debilitating drop in blood pressure upon standing that is associated with Parkinson's disease, multiple-system atrophy, and pure autonomic failure.

What is Northera?

Northera is a synthetic amino acid analog that is directly metabolized to norepinephrine, a vasopressor. Norepinephrine causes constriction (tightening) of the blood vessels which leads to an increase in blood pressure.

Northera is used to treat neurogenic orthostatic hypotension, reat a rare, chronic condition characterized by a sudden drop in blood pressure when a person stands.

What is the most important information I should know?

Northera may cause an excessive increase in blood pressure when lying down (supine hypertension), which could lead to strokes, heart attacks and death. You must rest and sleep with your upper-body in an elevated position while you are taking this medicine. You should also monitor your blood pressure regularly.

Contact your doctor immediately or seek emergency medical attention if you experience an unusual awareness of heartbeats, pounding in the ears, headache, or blurred vision. These may be signs of increased blood pressure.

In some cases, increased blood pressure may cause a slowed heart rate. Contact your doctor immediately or seek emergency medical attention if you experience decreased pulse rate, increased dizziness, fainting, or an unusual awareness of heartbeats. These may be signs of a slowed heart rate.

Northera can cause elevated blood pressure when lying down. The last dose should be taken at least three hours before bedtime. If you are going to be lying down for any length of time during the day, you may need to skip a dose. Talk to your doctor about how to take Northera if you lie down during the day.

Other prescription and over-the-counter medicines may cause an increase in blood pressure , which may be dangerous when taken with Northera. Do not take any other prescription or over-the-counter medicines or herbal products especially cough, cold, or allergy products, weight loss products, asthma or respiratory medicines, migraine headache medicines, heart or blood pressure medicines, or antidepressants without first talking to your doctor.

How to control the brain:

How to control the brain: Kelly Foote and Michael Okun at TEDxUF

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How to control the brain:

Neurologist Kelly Foote and neurosurgeon Michael Okun research direct brain stimulation -- strategically implanting electrodes inside the skulls of their patients to alleviate symptoms of tremor, multiple sclerosis and even OCD. The technology could also potentially control emotions. Together, they propose a guiding ethical principle for the technology.

Added Apr 18, 2012

What is "Wearing Off" ?

Due to their proven efficacy, levodopa therapies are prescribed eventually to most people with Parkinson’s disease (PD). However, long-term use of levodopa may give rise to certain complications where symptom control fades out causing the effect of the drug to wear off.

Figure 3. Typical pattern of wearing off during the day in someone having PD

Wearing off’, ‘fading effect’ and ’end-of-dose effect’ all describe the same inconvenient situation where levodopa no longer seems to work as effectively as it used to. In the early days of treatment with levodopa, people with PD experience a period where the Parkinson’s symptoms are well controlled for the entire day5. This is a time when people often feel contented with their treatment and is commonly referred to as the ‘honeymoon period’. However, over the years, the effect of levodopa seems to fade and symptom control may become more irregular (Figure 3). During this period of wearing off, the medicine seems to suddenly stop working, allowing Parkinson’s symptoms to re-emerge and worsen before the next dose of levodopa is due (Figure 3). Because this fading effect is usually seen towards the end of the dose period, wearing off is also referred to as the ‘end-of-dose effect’.

Video

The Parkinon’s symptoms that tend to return during wearing off may include both motor and non-motor symptoms such as tremor, stiffness, slowness, shuffling, muscle cramping, reduced dexterity and agility, mood changes, slowness of thinking, anxiety or even pain at the end-of-dose period.

As Parkinson's disease (PD) progresses, levodopa appears to become less effective in eliminating motor symptoms. Eventually the duration of “on” states becomes shorter and “wearing off” happens sooner than when the person takes a dose of levodopa. In an "off" state, the person becomes very stiff, slow and may even be unable to move for a few minutes. In some persons with PD, the "on-off" fluctuations are somewhat predictable. They know that the effects of levodopa will wear off after about three hours, so they can plan accordingly. For other people, the "on-off" fluctuations are unpredictable, and this of course is the more dangerous state. No one knows why fluctuations are unpredictable in some cases. Motor fluctuations seem to respond to controlled-release forms of levodopa.

                                                                        *************

One of the mainstays of treating Parkinson’s disease is levodopa. However, over time, sufferers and their caregivers may find that the drug does not work as well as it did to begin with. Slowness, tremor and other symptoms begin to reappear between doses. This effect, known as levodopa “wearing-off”, is because the brain cells that produce dopamine from levodopa do not function as they did originally. People with Parkinson’s disease can clearly recognize when the drug is working effectively – i.e. they are “on” – and when it is not – they are “off”.

Over the years, several strategies have been developed to deal with the wearing-off problem. Increasing the levodopa dose helps, but it may produce more side effects, especially involuntary movements (dyskinesias). The daily dose of levodopa can be divided into smaller amounts given more frequently, but there are practical limitations to this. Control-release levodopa preparations are available, and are helpful in some people, but their absorption into the body is not always constant, so that responses sometimes fluctuate. Addition of a dopamine agonist (bromocriptine, pergolide, ropinerole) can also help, by directly stimulating the dopamine receptors in the brain; however, these drugs are not as powerful as levodopa.

A new approach is the use of what are known as COMT inhibitors. COMT is an enzyme that breaks down levodopa in parts of the body other than the brain, so that blocking it means that more levodopa from a given dose is available to be converted to dopamine within brain. In other words, these drugs make more efficient use of levodopa by prolonging the effect of each dose.

A clinical study done in Scandinavia has been published which involves one of these drugs, entacapone. It demonstrates quite clearly the benefits achieved by a COMT inhibitor in patients with levodopa wearing-off symptoms.

Over a six-month period, more than 150 people with Parkinson disease with wearing-off symptoms – average age 62 years – were given either entacapone or a dummy matching Tablet (placebo), along with each dose of levodopa that they were taking. They had to be taking 4 to 10 daily doses of levodopa, and have an average “on” time after each dose of less than four hours. Their dose of levodopa could be adjusted during the study, as necessary.

The participants in the study visited the neurologist 6 times during the study, as well as 2 weeks after the end of the drug treatment. For 5 days before each visit they completed a daily diary in which they recorded the effect of the first morning levodopa dose, and the “on”, “off”, or “in bed” status for each half hour during the 24 hours. They also completed questionnaires and physical exams at the first and the last visit, and underwent a battery of lab tests.

The main analyses consisted of averaging the total daily “on” time and the “off” time after the first morning levodopa dose, using the diary information. Other effects were also analyzed, including participants’ assessments of the benefit from a single levodopa dose, and their overall assessment of treatment over the six months.

The average total daily “on” time increased by 70 minutes more in the patients given entacapone than in those given the dummy tablets. Similarly, the total “off” time decreased by 80 minutes more with entacapone than with placebo. Both these effects were highly significant. The participants described significantly greater overall benefits with entacapone than with placebo. Two weeks after the end of the study, the increases in the duration of levodopa effects had disappeared.

Entacapone was associated with some nausea and diarrhea in as many as 20% of those taking it, but these effects were also seen in over 7% percent of the people taking the placebo. Some worsening of the side effects of levodopa occurred, but lowering the actual levodopa dosage was able to reduce this. Otherwise, entacapone produced no side effects.

The results of this study support the underlying theory that the use of entacapone can improve life for Parkinson patients with wearing-off symptoms. There have been some reports of liver toxicity with another COMT inhibitor, tolcapone, and patients taking it should have tests of liver function every few weeks during the first year of treatment. To date, there have been no reports of liver toxicity with entacapone, which may therefore represent a more satisfactory approach to the wearing-off problem.

Orignally posted on Telemanagement - http://www.tele-management.ca/2013/08/parkinsons-disease-dealing-with-wearing-off/

The Many Types of Pain in Parkinson's Disease

In the past, many descriptions of Parkinson’s disease didn’t mention pain as being a significant symptom, the standard explanations usually focusing on the motor aspects of the disease. Of course these definitions are not incorrect but this disease challenges us in many ways and dealing with pain, is no exception.  And it is one issue that often significantly affects quality of life, which is something none of us want to lose…it is much too important and unfortunately very often, difficult to maintain.  Yet we continue to pursue it, committed to remaining as active and productive for as long as this disease allows. 

Pain in fact is a frequent complaint in PD.  It is estimated that 35 – 80% of Parkinson’s patients experience significant discomfort.  This statistic represents quite a wide variability due to difficulty in studying something as subjective as pain – lack of standardized definitions and consistent assessment tools being real challenges.  Regardless of its prevalence, by restricting mobility, interfering with sleep and affecting mood among other issues, pain in Parkinson’s can interfere with an individual’s daily functioning and life.

Most of the time, discomfort in muscles and joints is secondary to the motor features of Parkinson’s - lack of spontaneous movement, rigidity and abnormalities of posture –what is known as musculoskeletal pain.  The most commonly painful sites are the back, legs and shoulders and it is usually more predominate of the side more affected by parkinsonism.

But there are many other categories of pain associated with Parkinson’s disease.  Radicular or neuropathic pain is experienced as numbness or tingling, or a sensation of coolness in a part of the body, usually secondary to a pinched nerve because of something like a slipped disc or in some Parkinson’s patients is due to the strong and prolonged muscle spasm that can occur.

 Dystonia – related pain occurs as its name suggests, at times of dystonia (prolonged, painful contraction of a muscle) most often experienced in the foot, neck or face and arm at different points in the dosing schedule, particularly the “off” phase when there is not enough dopamine replacement but can uncommonly also occur at peak-dose times. It can be one of the most painful symptoms those with Parkinson’s can face.

Akathitic pain is experienced as restlessness, a subjective inner urge to move, an inability to stay still and the inherent feelings of discomfort that it brings.  It is primarily experienced in the lower limbs and can often be relieved by walking around.

Primary or central pain in Parkinson’s is a direct consequence of the disease itself and is not due to secondary causes.  It can be described as a painful, burning, stabbing, aching, itching or tingling occurring in undefined areas of the body.  This type of pain can be quite relentless and distressing.

Most often it is a combination of many different causes (multifactorial) but regardless of the type of pain, its presence can adversely affect health-related quality of life measures and in some people can even overshadow the motor symptoms of the disease.

And fact is that even though it has a significant detrimental effect on quality of life, pain in Parkinson’s is often undertreated.  Diagnosing the source of pain in Parkinson’s disease can be difficult and is often a diagnosis of exclusion, meaning that all other possible non-PD related causes are ruled out first.  But once diagnosed and classified, management can be directed towards treating the potential cause or at least relieving some of the debilitating symptoms.

There are interventions that you can implement in order to alleviate some of the discomfort along with a number of medication adjustments or additions that your physician can attempt that may also be of some benefit.  Pain in Parkinson’s disease is a real and serious phenomenon.  Minimizing the amount of pain that you experience is a necessity and a worthwhile focus for you and members of your health team.

References Used:

Ford, Blair, MD. "Pain in Parkinson's Disease." Weblog post. Parkinson's Disease Foundation. N.p., Winter 2005. Web.

 Olanow, C. W., MD, F. Stocchi, MD, and Anthony E. Lang, MD. "Pain and Paresthesia in Parkinson's Disease." Parkinson's Disease: Non-motor and Non-dopaminergic Features. Chichester, West Sussex, UK: Wiley-Blackwell, 2011. 315-32. Print.

 Sorbo, Francesca Del, MD, and Alberto Albanese, MD. "Clinical Management of Pain and Fatigue in Parkinson's Disease." Parkinsonism & Related Disorders 18 (2012): S233-236. Web.