Differentiating Parkinson's disease from atypical parkinsonism - simple clinical tests

Two simple tests conducted during the neurological exam can help clinicians differentiate between early-stageParkinson's disease (PD) and atypical parkinsonism. By asking patients to perform a tandem gait test and inquiring whether they are still able to ride a bicycle, clinicians can ascertain whether medio-lateral balance is impaired, a defining characteristic of atypical parkinsonism. These findings are published in the Journal of Parkinson's Disease.

This issue of the Journal of Parkinson's Disease also marks the inauguration of a new feature, "How I examine my patient," which is designed to help improve the clinical skills of physicians, allied health professionals, and other professionals involved in the care of patients with PD and other movement disorders.

The occurrence of a sideways or medio-lateral balance impairment is a "red flag" of atypical parkinsonism conditions, such as multiple system atrophy (MSA), progressive supranuclear palsy, or vascular parkinsonism. As the condition progresses, patients with this deficit often compensate by adopting a wide-based walking pattern, probably reflecting widespread pathologic brain involvement of the cerebellum and brain stem, explains Jorik Nonnekes, MD, of the Radboud University Medical Center, Department of Rehabilitation, Nijmegen, the Netherlands.

In contrast, patients with PD develop a shuffling gait, maintaining a narrow distance between their feet. Because medio-lateral balance is preserved, a PD patient may still be able to ride a bicycle even when walking is difficult.

In the first test, 36 patients with PD and 49 patients with atypical parkinsonism were given a tandem gait test. Patients were instructed to take 10 consecutive steps along an imaginary straight, thin line, toe-to-heel. An abnormal tandem gait was scored if one or more side steps were needed to maintain balance. The researchers found that 18% of patients with atypical parkinsonism were able to perform the tandem gait test without a single side step, compared with 92% of patients with PD. The results were similar for patients with only early disease (< 3 years).

Another study included 45 patients with PD and 64 patients with atypical parkinsonism, all of whom said they previously rode bicycles before the onset of motor symptoms. When asked if they still were able to ride a bicycle, 52% of the atypical parkinsonism patients said they had stopped cycling compared to 2% of those with PD.

"Both tests are easy to perform in clinical practice and have a good diagnostic accuracy, even early in the course of the disease," says Dr. Nonnekes. He adds that the tests should always be judged in the clinical context and presence of other red flags or supportive features.

In the new "How I examine my patient," feature researchers and clinicians will contribute practical information about how to conduct good neurological examinations. In many cases, the literature and even neurological textbooks do not include practical descriptions of very common clinical tests.

In the first example, "How I examine my patient: The art of neurological examination for Parkinson's disease and atypical parkinsonism," authors Bastiaan R. Bloem, MD, PhD, Department of Neurology, Radboud University Nijmegen Medical Center, the Netherlands, and Patrik Brundin, MD, PhD, Laboratory of Translational Parkinson's Disease Research, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, discuss how a well-done examination provides important diagnostic information. They write, "Details about how to perform certain clinical tests can be retrieved from standard neurological textbooks, but many useful clinical tips and tricks have been simply transmitted from teacher to student...such clinical pearls were never laid down in accessible form for a broad readership.

"We hope this new section offers readers a glimpse into the examination room of experienced clinicians who share their clinical pearls," say Dr. Bloem and Dr. Brundin.

Adapted by MNT from original media release

http://health.einnews.com/article/235642384

Cynapsus reports positive top-line results from CTH-105 phase II trial of APL-130277 to treat Parkinson's Disease

Published 20 November 2014

Cynapsus Therapeutics, a specialty pharmaceutical company focused on Parkinson’s disease, announced positive top-line results from its CTH-105 Phase II clinical trial of APL-130277 for the management of OFF motor symptoms of Parkinson’s disease.

APL-130277 is the Company's fast-acting, sublingual, thin filmstrip formulation of apomorphine. OFF episodes are a complication of Parkinson's disease that leave patients rigid and unable to move and communicate.

An estimated one quarter to one half of all people with Parkinson's disease whose symptoms are otherwise managed with ongoing drug therapy, experience OFF episodes at least once daily and up to six times daily, with each episode lasting between 30 and 120 minutes.

"The purpose of the CTH-105 study was to better understand the APL-130277 dose range that produced efficacy as measured by the change in the Unified Parkinson's Disease Rating Scale (UPDRS) part III, a scale used by neurologists to measure the severity of Parkinson's disease OFF and motor symptoms, compared with baseline. We are encouraged that APL-130277 provided clinical benefit at all five doses used in this study," said Dr. Albert Agro, Chief Medical Officer of Cynapsus.

"These preliminary data show that APL-130277 was able to convert patients from a severe OFF state in the morning to ON. In addition, treatment was associated with a 45% improvement in motor function based on the change in UPDRS part III from baseline. The mean dose needed to terminate the OFF episode was 18.4mg. In addition, those patients achieving a response at higher doses appeared to adapt to the treatment, as seen by the lack of nausea at higher doses."

In the CTH-105 multicenter open-label study, APL-130277 was assessed in 16 patients with Parkinson's disease who experience the debilitating effects of OFF episodes, with a total duration of OFF of at least two hours daily.

To date, 16 patients have completed the dosing regimen, which was the planned sample size for the study. Due to over enrollment, an additional three patients are still in dosing. OFF episodes were achieved by having patients take their last dose of levodopa the night before they came into the clinic.

Patients were not allowed to take their first dose of levodopa in the morning, resulting in a severe OFF state that is one of the most difficult to convert and maintain in an ON state.

Patients were then given escalating doses of APL-130277 (at a minimum of three hours between doses) until ON was achieved, as documented by study staff, the patient, and a clinician assessment of UPDRS part III. The UPDRS III part score was measured at 15, 30, 45, 60 and 90 minutes.

All five doses of APL-130277 used in the study (10, 15, 20, 25 and 30mg) resulted in patients moving from OFF to ON. The mean baseline UPDRS part III in an OFF state was 41.4, and the maximum mean change from baseline UPDRS part III was 18.4.

The mean dose required to convert patients to ON was 18.4mg. The onset of a clinically meaningful improvement was seen in as early as 10 minutes and lasted up to 90 minutes, the last time point measured in this study.

The mean time to ON as reported by study staff was 22 minutes. Cynapsus believes that these data strongly support the conclusion that APL-130277 is associated with the robust and rapid management of OFF episodes.

The graph below (click the multimedia link) shows the mean change from baseline in UPDRS part III for the 14 subjects who converted to ON. Two patients dosed at the highest available dose (30mg) did not achieve a full ON as assessed by the investigator, suggesting that higher doses may be required for some patients.

Treatment with APL-130277 was safe and well tolerated. Nausea was reported by three subjects at doses of 10, 15 and 20mg. One of these patients also experienced a mild episode of emesis. There were no reports of nausea at higher doses. There were no reports of local irritation or hypotension in any subject treated. A total of 60 doses of APL-130277 were administered to the 16 patients who completed dosing in the CTH-105 study.

Based on the findings of this study, Cynapsus is planning to conduct pivotal studies of longer duration and with larger patient numbers to confirm these results. These pivotal studies are expected to form the registration package necessary for a 505(b)(2) New Drug Application with the U.S. Food and Drug Administration expected to be submitted in 2016.

"The results of this Phase 2 trial are important as the data show that APL-130277 provided Parkinson's patients with a rapid improvement in motor function during OFF episodes," said Anthony Giovinazzo, President and CEO of Cynapsus.

"APL-130277 is being developed to address a significant unmet need facing people with Parkinson's disease today. The CTH-105 trial results lead us to maintain that APL-130277 may be able to serve the majority of Parkinson's patients seeking to restore movement rapidly, on demand, with an easy to retrieve and to administer form of apomorphine, the only approved and most efficacious drug for this purpose."

"OFF episodes are debilitating events for people with Parkinson's disease. A recent survey by The Michael J. Fox Foundation of 3,000 Parkinson's patients revealed that nearly half said their OFF time was moderate or severe, causing them to avoid or stop activities," said Dr. Todd Sherer, CEO of The Michael J. Fox Foundation for Parkinson's Research, which provided $500,000 in funding for this study.

"A rapid and reliable therapy that can address OFF episodes would be a major advancement in treatment. These results suggest that APL-130277 could provide patients with improved quality of life, and as supporters of this program from its early days, we look forward to continued success in Phase 3 trials."

th.einnews.com/article/235693406/oa1KT4UfRQ3tBYms?n=2&code=ga_qGBxHZ2aVYO4P

Housework, Commute Linked to Parkinson's Disease

People who are active are less likely to develop Parkinson's disease, according to a new study.

After following 43,368 people in Sweden for an average of 12.6 years, researchers found that even "a medium amount" of physical activity significantly lowers the risk of the neurodegenerative disorder.

The latest involved data from 27,863 females and 15,505 males participating in the Swedish National March Cohort. None of the participants had Parkinson's disease at the start of the study. Participants were followed from Oct. 2007 to Dec. 2010.

Researchers identified 286 participants who developed Parkinson's disease. 

Further analysis revealed that people who spent more than six hours a week on household and community activity were 43 percent less likely to develop Parkinson's disease compared to those who spent less than two hours per week on the same types of activities. The study also revealed that men with "a medium level" of total physical activity were 45 percent less likely to develop Parkinson's disease. The study defined moderate physical activity as performing an average of 39.1 metabolic equivalent hours per day. Metabolic equivalent is determined by quantifying the estimated oxygen consumption associated with physical activity.

"Our study has a number of strengths. This was a prospective study including both males and females, and all information on physical activity was assessed before the disease occurrence, making recall bias and reverse causation less likely," study author Karin Wirdefeldt, researcher at the Department of Medical Epidemiology and Biostatistics and Department of Clinical Neuroscience, said in a news release.

"Another major strength of this study is that we considered the entire spectrum of daily energy output, rather than purely focusing on dedicated exercising. Further, we conducted a rich set of sensitivity analyses to test the robustness of our findings," she noted.

"We found that a medium level of daily total physical activity is associated with a lower risk of Parkinson's disease. The protective effect of physical activity was further supported when we summarized all available evidence from published prospective cohort studies. These findings are important for both the general population and for the healthcare of patients with Parkinson's disease," Wirdefeldt concluded.

The latest study was published online in Brain: A Journal of Neurology.

Read more: http://www.counselheal.com/articles/13354/20141120/housework-commute-linked-parkinsons-disease.htm#ixzz3JihViRPn

Consider Restless Genital Syndrome in Parkinson's

the Neurology Advisor take:

Parkinson’s disease (PD) is rarely associated with discomfort in the genital region; however, researchers suggest that restless genital syndrome should be a part of the differential diagnosis in PD patients, according to a study published in JAMA Neurology. 

Restless genital syndrome, sometimes also referred to as persistent genital arousal disorder (PGAD), causes feelings of pain, discomfort, tingling and burning sensations in the genital region and can be disabling and very distressing to patients. 

A woman aged 65 years with PD complaining of severe and persistent discomfort in the genital region. Symptoms occurred at night and were often triggered by sitting or lying down for periods of time. During examination, no gynecological abnormalities were observed. She was treated with a low dose of a dopamine agonist and reported improvement.

Although the disorder is rare, researchers suggest that restless genital syndrome be included in the differential diagnosis of genital symptoms and restlessness, as well as nonmotor wearing off and akathisia. Treatment with dopamine agonists can improve symptoms. 

In PD, Restless Genital Syndrome Should Be Considered

In this case study, Camila C. Aquino, MD, MSc, of the Morton and Gloria Shulman Movement Disorders Center at Toronto Western Hospital in Ontario, Canada, and colleagues observed a female Parkinson's disease patient complaining of severe and disabling symptoms in the genital region, including burning sensations, tingling and pain. Previous rare cases were attributed to nonmotor off symptoms.

While restless genital syndrome is rare, researchers suggest that it be included in the differential diagnosis of genital symptoms and restlessness, and recommend treatment with a dopamine agonist. 

http://www.neurologyadvisor.com/restless-genital-syndrome-in-parkinsons-disease/article/376826/

Weight, eating habits in Parkinson's disease

November 20, 2014

 Source:

Sissa Medialab

A review of the scientific literature on Parkinson's disease, conducted by SISSA research scientists, shows that even the non-motor symptoms associated with the disease can contribute to the changes in body weight seen in patients (including those subjected to deep brain stimulation). Among the factors affecting eating habits and body weight there could be, for example, an impaired ability to derive pleasure from food and changes in motivation. These are important findings which can help to understand how to reduce these effects of Parkinson's that exacerbate an already negative clinical situation

Patients affected by Parkinson's disease often show marked changes in body weight: they may gain or lose a lot of weight depending on the stage of the disease, or they may put on up to ten kilos after deep brain stimulation (a treatment to alleviate the symptoms). This situation considerably worsens the quality of life of a person who is already suffering from heavily disabling motor disorders, so it is important to understand what are the factors that cause it.

"The body weight and eating habits of Parkinson's patients change as the disease progresses," explains Marilena Aiello, SISSA researcher and first author of the study published in the journal Appetite. "In our paper, we reviewed studies on Parkinson's that provided data on the association between non-motor symptoms and dietary habits and body weight. This way, we were able to evaluate some factors which, beyond the motor symptoms and drug treatments, might play a role in this problem."

Depression, cognitive impairment, sensory disturbances -- chiefly smell and taste -, impaired ability to feel pleasure: all these aspects contribute to incorrect eating habits. "The possible role of the ability to feel pleasure and motivation towards food consumption is particularly interesting. Parkinson's patients may be somewhat lacking in this respect and therefore eat less and lose weight, whereas the weight gain exhibited after deep brain stimulation seems to point to an increase in pleasure and motivation associated with food. Specific studies are required to confirm or refute this finding emerging from the literature review."

"Studies like ours can help those working with these patients: awareness of the roles played by the different factors is in fact crucial for devising interventions aiming to minimise the effect of the deficits and restore normal weight levels in individuals who are already suffering because of the disease."

end text

Story Source:

The above story is based on materials provided by Sissa Medialab. Note: Materials may be edited for content and length.

end story_source

Journal Reference:

1  Marilena Aiello, Roberto Eleopra, Raffella I. Rumiati. Body weight and food intake in Parkinson's disease. A review of the association to non-motor symptoms. Appetite, 2015; 84: 204 DOI: 10.1016/j.appet.2014.10.011

end journal_references

Cite This Page:

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Sissa Medialab. "Weight, eating habits in Parkinson's disease." ScienceDaily. ScienceDaily, 20 November 2014. <www.sciencedaily.com/releases/2014/11/141120082138.htm>.

Video games, Parkinson's 'therapy'

Computer consoles can help improve the lives of people with the neurological disease Parkinson's, researchers have found.

A patient testing a mini golf game (Lancaster University/PA)

Scientists said games with sensors - used in consoles like the Nintendo Wii and accessories such as the Xbox Kinect - were found to aid symptoms of those with the degenerative brain condition taking part in the study.

An in-depth study with Parkinson's sufferers at Lancaster University found that video games involving the movement of players acted as a form of physical therapy.

Researcher Dr Emmanuel Tsekleves said: "Muscles and joints tend to become stiff and rigid, which is why exercise is crucial in managing some of the symptoms.

"However, physiotherapy exercises are very repetitive in nature leading to boredom and de-motivation and hence lack of adherence.

"Computer games have the potential to motivate people to keep active by implicitly incorporating repetitive exercises into the games."

Parkinson's disease affects more than 120,000 people in the UK, and six million across the globe.

Sufferers include former boxing champion Muhammad Ali, comedian Billy Connolly , and actor Michael J Fox.

Researchers have been adapting and testing computer games to be used as physical therapy and believe people with Parkinson's should be involved in the design of these games.

Dr Tsekleves said: "Our research involved participants with Parkinson's using commercially available gaming sensors like the Nintendo Wii and computer games designed specifically for people with Parkinson's disease.

"The key was in taking physiotherapy exercises and translating them into game play movements.

"The games help at improving the player's speed and arm movement, improving flexibility and reducing rigidity.

"One involved the control of a two-paddled row boat, while the second, the steam mini-golf game, asked the player to rotate a valve to release steam to push a ball into a hole."

The researchers, who also included teams from Brunel University and Queen's Belfast, found that the more familiar games based on simple exercises worked best.

Commenting on the study, Professor David Burn, Parkinson's UK clinical director, said: "Studying the effects of exercise on Parkinson's is an underexplored but exciting area of research.

"We know that games like those on Nintendo Wii can be a great way to help people with Parkinson's improve their stiff movement, as well as their general fitness levels.

"This study is only in a handful of people, and needs to be replicated in larger numbers, but the results are promising."

Earlier this year, e xperts at Newcastle University began investigating the benefits that Google Glass could have on Parkinson's sufferers.

The technology works like a hands-free smartphone displaying information on the lens of the glass.

http://jerseyeveningpost.com/news/uk-news/2014/11/20/video-games-parkinsons-therapy/

A medium amount of physical activity can lower the risk of Parkinson's disease

November 19, 2014 - 12:31am

A new study, published online in Brain: A Journal of Neurology today, followed 43,368 

individuals in Sweden for an average of 12.6 years to examine the impact of physical 

activity on Parkinson's disease risk. It was found that "a medium amount" of physical 

activity lowers the risk of Parkinson's disease.

Karin Wirdefeldt of the Karolinska Institutet in Stockholm and her colleagues used the 

Swedish National March Cohort to analyse comprehensive information on physical 

activity of all kinds. They assessed household and commuting activity, occupational 

activity, leisure time exercise, and total daily physical activity according to data 

provided by 27,863 females and 15,505 males as part of an extensive questionnaire. 

For the purpose of this study, physical activity was quantified into metabolic equivalent 

(MET) hours per day, based on estimated oxygen consumption associated with those

 activities.

All participants were free of Parkinson's disease on 1 October 1997, the start of the 

follow-up period. Study participants were followed from this baseline until date of 

diagnosis with Parkinson's disease, date of death, date of emigration, or the end of 

the follow-up period on 31 December 2010, whichever came first. In that time 286 

cases of Parkinson's disease were identified.

In the study's multivariable-adjusted model, compared with participants who spent 

less than two hours per week on household and commuting activity, those who spent 

more than six hours per week on the same types of activities had a 43% lower risk of 

developing Parkinson's disease. Compared with a low level of total physical activity, a 

medium level of total physical activity (a mean of 39.1 MET hours per day) was 

associated with a 45% lower Parkinson's disease risk in males. Leisure time exercise 

was not associated with Parkinson's disease risk when analysed alone. 

Karin Wirdefeldt, researcher at the Department of Medical Epidemiology and 

Biostatistics and Department of Clinical Neuroscience, who headed the study, said: 

"Our study has a number of strengths. This was a prospective study including both 

males and females, and all information on physical activity was assessed before the 

disease occurrence, making recall bias and reverse causation less likely." 

"Another major strength of this study is that we considered the entire spectrum of daily 

energy output, rather than purely focusing on dedicated exercising. Further, we 

conducted a rich set of sensitivity analyses to test the robustness of our findings."

"We found that a medium level of daily total physical activity is associated with a lower 

risk of Parkinson's disease. The protective effect of physical activity was further 

supported when we summarized all available evidence from published prospective 

cohort studies. These findings are important for both the general population and for 

the healthcare of patients with Parkinson's disease."

Source: Oxford University Press

http://www.sciencecodex.com/a_medium_amount_of_physical_activity_can_lower_the_risk_of_parkinsons_disease-145915