The Dream of a Pill Free Existence and the Continuous Dopaminergic Pump for the Treatment of Parkinson’s Disease

You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.

One of the common dreams shared by Parkinson’s disease patients around the globe is the possibility of living a pill free existence.  One cannot blame the Parkinson’s disease patient or caregiver for dreaming big.  A single day in Parkinson’s disease shoes is likely to reveal the need for dozens of pills administered day and night.   In many cases, pills are taken as frequently as every hour or two.  If you ask a Parkinson’s disease patient to place an entire pill regimen for the day into the palms of their hands, there is a better than average chance he or she will not be able to hold all of them.  Previously, there was a hope that deep brain stimulation may have offered the highly sought after “pill free existence,” however over two decades into its history, it is clear that in the majority of cases, medications will still be required.  There is however, another treatment strategy on the horizon.  A strategy that offers the possibility of constant stimulation of the brain’s dopamine receptors through the use of a continuous dopamine infusion pump technology.  In this month’s issue of Lancet Neurology the first randomized controlled trial of a continuous pump infusion technology for Parkinson’s disease has been published (online before print).

The trial utilized an intrajejunal (i.e. a tube inserted in the small intestine) levodopa-carbidopa intestinal gel pump infusion strategy, and it was designed to collect safety and effectiveness data.  The study was carefully conducted and was double blind (neither the patients nor the raters knew what was administered) and randomized.  It was conducted in 26 centers including Germany, New Zealand, and the US. Participants were randomized (1:1) to “immediate-release oral levodopa-carbidopa pills plus a placebo intestinal gel infusion or to levodopa-carbidopa intestinal gel infusion plus oral placebo pills.”  It is important to remember that everyone in the study received a pump, but half of the patients did not receive active therapy (through the continuous pump infusion). The authors were most interested in improving the amount of time spent in the “off state” following 4 months of therapy. Off-time improved by 4 hours in the pump group versus 2.1 hours in the pill group.  The amount of “on” time without troublesome dyskinesia was better in the pump group when compared to the pill group (4.1 vs. 2.2 hours).

The pump is approved and available in 43 countries.  The United States has lagged behind the world in adopting this new approach to Parkinson’s disease therapy.  However, in defense of the U.S.A. and the FDA, prior to the publication of the current pump trial, all previous results were based on uncontrolled evidence.  The benefits of the pump have been clearly demonstrated.  In this population of fluctuating patients, the data would suggest that the pump out-performs standard medical therapy.  The study did not enroll patients with severe dyskinesia, and it is unclear how the continuous infusion pump will perform in more severe and more disabled Parkinson’s disease patients.

One of the major drawbacks to the pump approach is the need for a percutaneous gatrojejunostomy (a small feeding tube).  These types of tubes can serve as nidus points for infections and other complications, and in the current study, device complications were present in 89% of subjects.  The complications were addressable in most cases, and were reported as lower than in previous pump trials.

Patients should be aware that the current version of the pump requires wearing an external device, and it also requires changing a dopamine cassette once or twice a day.  The dopamine cassettes are a little smaller than a cellular phone, and usually last about 14-16 hours.  Some patients will require two cassettes, and some will need additional medications during the bedtime hours.  The pumps require continuous maintenance and programming by a qualified professional.  The tube connected to the stomach also requires constant monitoring for infection.

If the continuous infusion approach receives FDA approval one important step will be to compare its effectiveness to that of deep brain stimulation therapy (DBS).  Patient selection for pumps versus DBS will be an immediate and critical unmet need.  One question will be whether the pump technology can help debilitated patients with and without cognitive dysfunction who may be excluded from DBS.

Patients should be aware that pumps are powerful symptomatic therapies, but not cures; and in most cases the continuous infusion pump will not address the dopamine resistant symptoms of walking, talking, and thinking.  Pumps have not been shown to delay disease progression.  The good news for the Parkinson’s disease community is that for a subset of patients a “pill free existence” may be on the horizon.

Posted: 2/3/2014 8:39:29 AM by Cathy Whitlock

 

This is a form to show that you are not intoxicated but have Parkinson's disease and your mannerism may look like you have had too much to drink.

 

 

 

 

 

 

 

 

VISUAL DISTURBANCES IN PARKINSON'S DISEASE

19th January 2014 - New research


Parkinsonism Related Disorders [2013] Dec 27 [Epub ahead of print] (P.Urwyler, T.Nef, A.Killen, D.Collerton, A.Thomas, D.Burn, I.McKeith, U.P.Mosiman
Visual symptoms are common in Parkinson's Disease but are frequently under-diagnosed. The detection of visual symptoms is important for differential diagnosis and patient management. The causes of visual symptoms divides between Parkinson's Disease and Parkinson's Disease drugs. Parkinson's Disease can cause visual disturbances by affecting the muscles of the eye. Parkinson's Disease drugs in excess can cause visual hallucinations. Recurring visual complaints emerged as risk factors predictive of the minor forms of hallucinations, but not recurrent complex visual hallucinations.
Researchers established the prevalence of recurrent visual complaints (RVC) and recurrent visual hallucinations (RVH) in Parkinson's Disease. The most common visual disturbances were found to be : double vision (in 18% of people with Parkinson's Disease), misjudging objects when walking (in 12%), words moving whilst reading (in 17%), and freezing in narrow spaces (in 30%), which was almost exclusively found in people with Parkinson's Disease. The same was true for recurring complex visual hallucinations and illusions, which were found in 17% of people with Parkinson's Disease. Recurring visual complaints were found in 43% of people with Parkinson's Disease. Recurring visual hallucinations were found in 29% of people with Parkinson's Disease. 

RESPIRATORY PROBLEMS IN PARKINSON'S DISEASE

23rd January 2014 - New review

The excessive muscle contraction that Parkinson's Disease causes can affect the muscles that control respiration. Consequently, the breathing rate in Parkinson's Disease can often not be sustained as well, and breathing efficiency can be reduced . There is often abnormal ventilatory control despite normal lung volumes and flows . Respiratory muscle strength and endurance also are decreased 
Due to the reduced respiratory capacity, people with Parkinson's Disease are more prone to the effects of pneumonia, which occurs more commonly than expected in Parkinson's Disease, but not because of Parkinson's DiseaseConsequently, pneumonia is the most common cause of death associated with Parkinson's Disease However, death certificates indicated that Parkinson's Disease was a substantial contributor to the cause of death in only 20% of people with Parkinson's Disease. For 80% of people there were other causes.

Association between parietal gray matter volume changes and early Parkinson's disease memory deficits - Medical News Today

Association between parietal gray matter volume changes and early Parkinson's disease memory deficits

Tuesday 21 January 2014 - 12am PST

Research by a team of investigators in Finland suggests that the free recall memory deficits common even in early stages Parkinson's disease (PD) are related to structural changes in the brain, specifically parietal cortical gray matter volume. Their findings are published in the current issue of the Journal of Parkinson's Disease.

"This study is one of the first to link a discrete area of the brain to a cognitive deficit in people at an early stage of PD, comments lead investigator Ulla Ellfolk, Department of Psychology and Logopedics of Abo Akademi University, and the Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland. "Clinical studies have shown that free recall is more strongly affected than language, performance on simple attention tasks, and visuospatial functioning in newly diagnosed PD patients."

In the current study researchers are using very precise MRI data to localize small brain areas that underlie memory deficits associated with PD. While impaired memory in PD patients has been associated with volume loss in several temporal lobe structures, including the entorhinal cortex, few studies have looked at brain gray matter volume in relation to specific cognitive tasks and even fewer have been able to correlate structural changes with deficits in learning or memory at the earliest disease stages.

One of the reasons previous studies may have failed lies in the memory task chosen for testing. The investigators could not find any correlation between gray matter volume and visual and verbal memory in patients with newly diagnosed PD using conventional memory tasks, but were able to find a significant correlation using a novel, non-intentional incidental memory task that measures free recall. To their surprise, degenerative brain changes in the parietal region were found only on the right side of the brain.

Twenty-eight patients with early PD (disease duration less than 3 years) and 28 healthy controls underwent MRI imaging and neuropsychological testing within a four-week interval. None of the patients were clinically demented and none manifested cognitive deficits that significantly impaired their daily life.

Results from neuropsychological tests showed that the PD patients were significantly impaired compared to controls on tasks that measured incidental free recall, intentional free recall, wordlist learning, and visuospatial control tasks. No differences were found for wordlist delayed recall, wordlist savings percent, and executive control tasks.

The investigators used voxel-based morphometry (VBM) of MRI images, a neuroimaging analysis technique that allows measurement of focal differences in brain anatomy, to see whether they could find brain changes associated with memory impairment. Overall, they could find no statistically significant difference between PD patients and controls in local gray matter volumes, confirming that the PD patients were at early stages of disease.

However, significantly lower scores on the incidental memory task were associated with smaller local gray-matter volume in the right parietal cortex for the whole group and for the PD group alone. No such relationship was found in the control group and no other associations were found for any of the other memory tasks.

To interpret these findings, it is important to understand how the incidental free recall test differs from other memory tasks. In this test, a participant is asked to name items 30-60 from the Boston Naming Test. Naming is followed by asking the subject to recall the previously named items. Unlike intentional memory tests, the subject is not told ahead of time that he will be asked to recall the items. Incidental memory tasks are therefore very similar to real life situations where we are able to recollect content, events, or contexts without a prior intention of memorizing them.

"The most prominent difference between the incidental task and the other memory tasks was the absence of an explicit instruction to memorize items. Thus, no external cues to focus attention on the visual items were available during encoding," says Ellfolk. "This free recall test in particular may be sensitive to right parietal deficits because the parietal region modulates attention to memory and the visual rather than semantic nature of the task is directed to the right side of the brain."

Mild cognitive impairment at Parkinson disease diagnosis linked with higher risk for early dementia

Mar. 25, 2013 — Mild cognitive impairment at the time of Parkinson disease (PD) diagnosis appears to be associated with an increased risk for early dementia in a Norwegian study, according to a report published Online First by JAMA Neurology, a JAMA Network publication.

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Patients with PD have an increased risk for dementia (PDD) compared with healthy individuals and researchers sought to examine the course of mild cognitive impairment (MCI) and its progression to dementia in a group of patients with PD. The Norwegian ParkWest study is an ongoing population-based study of the incidence, neurobiology and prognosis of PD in western and southern Norway, according to the study background.

The study by Kenn Freddy Pedersen, M.D., Ph.D., of Stavanger University Hospital, Norway, included 182 patients with PD monitored for three years. More patients with MCI than without MCI at baseline (10 of 37 [27 percent] vs. 1 of 145 [0.7 percent]) progressed to dementia during follow-up. Of those with MCI at baseline, 8 of 37 (21.6 percent) had MCI that reverted to normal cognition during follow-up, according to the study results.

The results also show that mild cognitive impairment at the one-year visit was associated with a similar progression rate to dementia (10 of 36 patients [27.8 percent] and reversion rate to normal cognition (7 of 36 [19.4 percent]). Of the 22 patients with persistent MCI at baseline and the one-year visit, 10 (45.5 percent) developed dementia and only two (9.1 percent) had MCI that reverted to normal cognition by the end of the study.

"This prospective population-based study of an incident PD cohort demonstrates that MCI within the first year of PD diagnosis signals a highly increased risk for early incident dementia. More than 25 percent of patients with MCI at diagnosis of PD developed dementia within three years of follow-up compared with less than 1 percent of patients without MCI at PD diagnosis. Among patients with MCI at baseline and one year of follow-up, almost half progressed to dementia. These findings support the validity of the MCI concept in patients with early PD," the study authors conclude.

Editorial: Can Mild Cognitive Impairment in Parkinson Predict Dementia

In a related editorial, Brian J. Copeland, M.D., and Mya C. Schiess, M.D., of the University of Texas Medical School at Houston, write: "The term mild cognitive impairment (MCI) emerged in the 1990s, defining a transition state from normal cognitive function and forcing our appreciation of cognitive changes not attributable to age, education, sex, race, ethnicity, language, or culture, but rather to a well-defined disease process or related pathology."

"Cognitive impairment in PD is common, and the use of uniform criteria for the PD-MCI diagnosis is important in furthering research, predicting the development of dementia, and developing clinical trials to test therapeutic interventions. Stable PD-MCI over time may be a prognostic factor in the later development of PDD. However, the findings from the study by Pedersen and colleagues are based on a homogenous population of patients with early PD, and generalization of the results is uncertain," they conclude.

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Blood biomarker could mark severe cognitive decline, quicker progression among Parkinson’s patients

Sep. 18, 2013 — A genetic mutation, known as GBA, that leads to early onset of Parkinson’s disease and severe cognitive impairment (in about 4 to 7 percent of all patients with the disease) also alters how specific lipids, ceramides and glucosylceramides are metabolized. Mayo Clinic researchers have found that Parkinson’s patients who do not carry the genetic mutation also have higher levels of these lipids in the blood. Further, those who had Parkinson’s and high blood levels were also more likely to have cognitive impairment and dementia. The research was recently published online in the journal PLOS ONE.

 

The discovery could be an important warning for those with Parkinson’s disease. Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s disease. There is no biomarker to tell who is going to develop the disease -- and who is going to develop cognitive impairment after developing Parkinson’s, says Michelle Mielke, Ph.D., a Mayo Clinic researcher and first author of the study.

Cognitive impairment is a frequent symptom in Parkinson’s disease and can be even more debilitating for patients and their caregivers than the characteristic motor symptoms. The early identification of Parkinson’s patients at greatest risk of developing dementia is important for preventing or delaying the onset and progression of cognitive symptoms. Changing these blood lipids could be a way to stop the progression of the disease, says Dr. Mielke.

There is a suggestion this blood lipid marker also could help to predict who will develop Parkinson’s disease and this research is ongoing.

“There is currently no cure for Parkinson’s, but the earlier we catch it -- the better chance we have to fight it,” says Dr. Mielke. “It’s particularly important we find a biomarker and identify it in the preclinical phase of the disease, before the onset even begins.”

Dr. Mielke’s lab is researching blood-based biomarkers for Parkinson’s disease because blood tests are less invasive and cheaper than a brain scan or spinal tap -- other tools used to research the disease.

 

Higher vitamin D levels associated with better cognition, mood in Parkinson's disease patients

Jan. 16, 2014 — A new study exploring vitamin D levels in patients with Parkinson's disease (PD) opens up the possibility of a new avenue of early intervention that may delay or prevent the onset of cognitive impairment and depression. The findings are published in the Journal of Parkinson's Disease.

Investigators conducted a cross-sectional analysis of 286 patients with PD and found that higher plasma vitamin D levels were associated with lower symptom severity, better cognition, and less depression in the entire group, but the relationships were even stronger in those who were not demented.

"About 30% of persons with PD suffer from cognitive impairment and dementia, and dementia is associated with nursing home placement and shortened life expectancy," says Amie L. Peterson, MD, of the Oregon Health and Sciences University. "We know mild cognitive impairment may predict the future development of dementia. Intervening in the development of dementia has the potential to improve morbidity and mortality in persons with PD."

In this analysis, which was an add-on study to an ongoing longitudinal study of neuropsychiatric function in people with PD, patients were given a battery of tests measuring global cognitive function, verbal memory, semantic verbal fluency, executive function, and depression. On the same day, serum 25-hydroxyvitamin D levels were measured. Of the 286 subjects, 61 were considered to be demented by a consensus panel based on the Diagnostic and Statistical Manual of the American Psychiatric Association (4th edition) and 225 were not demented.

For the entire group, significant negative associations were found between vitamin D levels and disease severity, as measured both by the Hoehn and Yahr Scale and the United Parkinson's Disease Rating Scale motor section. Mean vitamin D3 levels were higher in those who were not demented, although the differences did not reach statistical significance.

Investigators found that for the entire group, higher levels of serum vitamin D3 were associated with greater fluency for naming vegetables and animals and immediate and delayed recall on a verbal learning test. When the group was divided into those who were demented or not, significant findings with vitamin D were found for fluency and verbal learning only for those who were not demented. "The fact that the relationship between vitamin D concentration and cognitive performance seemed more robust in the non-demented subset suggests that earlier intervention before dementia is present may be more effective," says Dr. Peterson.

A significant negative association was also found for vitamin D levels and depression, as measured by the Geriatric Depression Scale, for both the entire group and those who were not demented. No significant relationship was found for those who were demented.

The authors point out that a cross-sectional study cannot determine causation: for instance, does low vitamin D affect cognitive performance, or are persons with more advanced PD and worse cognition less ambulatory, get less sun exposure, and subsequently have lower vitamin D? The study also did not consider if patients were taking vitamin D supplements.

Vitamin D's role in health has been a subject of considerable scrutiny in recent years. Low levels increase the risk of type 2 diabetes mellitus, multiple sclerosis, hypertension, cancer, and infections. Vitamin D receptors and its final converting enzyme have been found in human brain tissue, including the hippocampus, which plays a significant role in memory and learning.

PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most obvious symptoms are movement-related, such as involuntary shaking and muscle stiffness. Non-motor symptoms, such as worsening depression, anxiety, and sleep disturbances, can appear prior to the onset of motor symptoms.

 

The DDT Story

The DDT Story

DDT Spray

If there is a single pesticide almost everyone can name, it's DDT.

DDT was one of the first chemicals in widespread use as a pesticide. Following World War II, it was promoted as a wonder-chemical, the simple solution to pest problems large and small. Today, nearly 40 years after DDT was banned in the U.S., we continue to live with its long-lasting effects:

·         Food supplies: USDA found DDT breakdown products in 60% of heavy cream samples, 42% of kale greens, 28% of carrots and lower percentages of many other foods.

·         Body burden: DDT breakdown products were found in the blood of 99% of the people tested by CDC.

·         Health impacts: Girls exposed to DDT before puberty are 5 times more likely to develop breast cancer in middle age, according to the President’s Cancer Panel.

Banned for agricultural uses worldwide by the 2001 Stockholm Convention on Persistent Organic Pollutants, the use of DDT is still permitted in small quantities in countries that need it, with support mobilized for the transition to safer and more effective alternatives. The treatment of DDT under the Stockholm Convention is strongly supported by PAN and our international partners.

Rachel Carson highlighted the dangers of DDT in her groundbreaking 1962 book Silent Spring. Carson used DDT to tell the broader story of the disastrous consequences of the overuse of insecticides, and raised enough concern from her testimony before Congress to trigger the establishment of the Environmental Protection Agency (EPA).

Her work attracted outrage from the pesticide industry and others. Her credibility as a scientist was attacked, and she was derided as “hysterical,” despite her fact-based assertions and calm and scholarly demeanor. Following the hearings, President Kennedy convened a committee to review the evidence Carson presented. The committee's review completely vindicating her findings.

One of the new EPA's first acts was to ban DDT, due to both concerns about harm to the environment and the potential for harm to human health. There was also evidence linking DDT with severe declines in bald eagle populations due to thinning eggshells. Since DDT was banned in the U.S., bald eagles have made a dramatic recovery. 

Recently, Carson's work has again been targeted by conservative groups. Capitalizing on the iconic status of DDT, these groups are promoting widespread use of the chemical for malaria control as part of a broader effort to manufacture doubt about the dangers of pesticides, and to promote their anti-regulatory, free market agenda while attempting to undermine and roll back the environmental movement's legacy.

Many DDT promoters are also in the business of denying climate change.

Attacks on Carson from groups like The Competitive Enterprise Institute and Africa Fighting Malaria portray DDT as the simple solution to malaria, and blame Carson for “millions of deaths in Africa.” Many of these DDT promoters are also in the business of denying climate change and defended the tobacco industry by denying the health harms of smoking.

Human Health Harms

The science on DDT's human health impacts has continued to mount over the years, with recent studies showing harm at very low levels of exposure. Studies show a range of human health effects linked to DDT and its breakdown product, DDE:

·         breast & other cancers

·     male infertility

·     miscarriages & low birth weight

·     developmental delay

·     nervous system & liver damage

No 'Silver Bullet' for Malaria Control

The only remaining legal use of DDT is to control malaria-carrying mosquitoes. A devastating disease, malaria kills more than 800,000 people every year, the majority of deaths among children in Sub-Saharan Africa. Indoor spraying with DDT is one of a number of tools being used to control malaria around the world. Only in rare cases is it the most effective choice. 

Successful malaria control programs have been built all over the world using a variety of approaches that are affordable and appropriate to local needs. All include community involvement, appropriate technology and investment in public health capacity and education. These community-based, integrated solutions have proven successful in places as diverse as Mexico, Kenyaand Vietnam.

Unfortunately, vocal groups such as Africa Fighting Malaria continue to promote a simplistic "DDT or nothing" debate, ignoring on-the-ground evidence from around the world that more effective approaches are saving lives without putting communities in harm's way from exposure to the long-lasting chemical.

PAN works with international allies, governments and on-the-ground groups in Africa to mobilize resources and political will to combat malaria, and remains active in international legal processes to support the global phase out of DDT and promote the safest and most effective malaria control solutions. 

THE PREVALENCE OF MUSCULOSKELETAL PROBLEMS IN PARKINSON'S DISEASE

8th January 2014 - New research

Parkinsonism Related Disorders [2013] 19 (7) : 666-669 (Y.E.Kim, W.W.Lee, J.Y.Yun, H.J.Yang, H.J.Kim, B.S. Jeon)

The prevalence of musculoskeletal problems was found to be significantly higher Parkinson's Disease. Around two thirds of people with Parkinson's Disease have them. Only just over a quarter of people with Parkinson's Disease answered that their musculoskeletal problems were recovering.  Musculoskeletal problems also tended to receive less treatment when people had Parkinson's Disease.

Common sites of musculoskeletal problems were the lower back, shoulder and knee in that order. The lower back was the site of musculoskeletal problems in nearly half of people with Parkinson's Disease. The shoulder and knee were affected far less often. Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in people with Parkinson's Disease. Older age, being female, and having a higher score on the Unified Parkinson's Disease Rating Scale were associated with more musculoskeletal problems.