Finding a New Doctor

By maria.deleon—February 23, 2018 

As we start a new year, many of us might have enrolled in new insurance programs and discovered that their doctors are no longer in-network, even worse, not covered by your insurance plan. Due to the hostile environment in which medicine finds itself these days, perhaps your physician, like mine, has decided to move or retire leaving us a bit anxious over finding a new person we can trust. The longer we have been with a physician or the longer we have been battling with a chronic complex illness such as PD, the more daunting the task of finding the one that will mesh well with our expectations. I am in such a position at the moment having lost not one, but 3 physicians at the same time. Fortunately, I still have my movement disorder specialist (MDS) but have a bit of apprehension knowing full well that she will be retiring in next couple of years.

So how do we approach finding a new doctor?

• Ask other patients and friends in your circle who they see and trust.
• Sometimes you may not have a choice because there is only one MDS in your area or none in your state.
• Another alternative is to enroll in a study so that you not only contribute to neurosciences research but also get the added bonus of having a physician or team of healthcare providers.

You found someone – now what?

Keep in mind that it’s always difficult to start a new relationship, especially one in which you can be yourself and feel comfortable sharing intimate details.

You would not expect a new love interest to know all about you from day one. It takes time to get to know a person. Unfortunately, the same is true with establishing a relationship with a new provider. Look for chemistry. There are some people that you know you won’t like even if you get to know them better. If this is the case move on. You must approach it with an open mind. When it comes to complex conditions, especially if present long-term, you need at least 3 visits to begin forming a planeveryone is happy with and knowing the direction treatment will take.

There are two important elements to finding and establishing a good doctor-patient relationship:

1. Respect
2. Responsibility

In order to forge a long lasting meaningful relationship with your physicians, one must offer respect first. You have the expertise of one while they have the expertise of thousands. You would not take kindly to someone outside of your field telling you how to do your job. At the same time, your healthcare professionals should be equally respectful of your needs as well as the knowledge you have regarding your own body and illness.

Second, take responsibility for the way you feel, project yourself, and type of physician you are needing. Are you in need of a paternalistic figure? A partner? Or a friend? The best relationships are the ones that have elements of all 3; give you tough love when need it, listen intently to your wishes and provide comfort, while meeting you halfway in your battle against PD. Make feasible demands of your physician (e.g. not expect to be pain-free at first visit when you have been dealing with pain for years). Things can always be accomplished in a gradual manner and realistic expectations. Keep lines of communication open.

https://parkinsonsdisease.net/living/finding-a-new-doctor/

Wasp Venom Triggers Parkinson’s-Like Symptoms, Study Reports

 FEBRUARY 23, 2018  BY PATRICIA INACIO, PHD 

The venom of the emerald cockroach wasp is capable of triggering Parkinson’s-like features, particularly problems controlling movement, a California study reports.

Researchers said the findings on the venom’s toxins could lead to a better understanding of the mechanisms underlying Parkinson’s and new therapies.

Their study, “Ampulexins: A New Family of Peptides in Venom of the Emerald Jewel Wasp, Ampulex compressa,” was published in the journal Biochemistry.

The wasp gets its name from the prey it prefers — the American cockroach. When its stings, it injects venom into the cockroach’s brain and upper body, or thorax. The toxins cause a roach to lose part or all of its ability to control its muscles.

This state resembles what happens in Parkinson’s disease. And it is likely caused by the same mechanism— the abnormal functioning or death of dopamine-producing nerve cells, researchers said.

“Mechanisms underlying venom-induced hypokinesia [slowed movement] are currently unknown, but evidence implicates dopamine receptor dysfunction as a possible cause,” the team wrote.

A group of researchers led by Michael E. Adams of the University of California at Riverside set out to  identify which components of the wasp venom triggered the roach’s movement problems.

Their first step was to milk wasps for their venom. Then they analyzed it using a technique called liquid chromatography followed by mass spectrometry. This allows scientists to identify a substance’s biochemical, organic, and inorganic components.

The analysis dealt with venom toxins known as ampulexins. Researchers discovered a line of the toxins they weren’t unaware of.

To determine the toxins’ role in venom-triggered paralysis, they injected the most abundant venom peptide, called ampulexin-1, into cockroaches.

Before an injection, a cockroach needed on average of 9 volts of electricity to get it moving. After an injection, it took 13 volts. This suggested that the peptides help the wasp immobilize its prey.

In the future, the researchers hope to identify ampulexins’ molecular targets. Another possibility is coming up with a new animal model to study Parkinson’s and test potential therapies.

https://parkinsonsnewstoday.com/2018/02/23/wasp-venom-parkinsons-like-symptoms/

Wearing Your Heart on the Outside

 FEBRUARY 23, 2018   BY "SHERRI WOODBRIDGE"

I used to wear my heart on my sleeve for all to see … and comment on. Not that I wanted to. Who am I kidding? I still wear my heart on my sleeve for all to see … and comment on. Not that I want to.

It is a curse, one might say, to be so vulnerable. It is a curse in the sense that you want to keep feelings that are so deeply felt hidden away so no one can see. Really; so they can’t mock, tease, or condemn. At least, it feels that way, sometimes.

It is a curse in the sense that you want to keep those feelings, so deeply felt, hidden so that you don’t have to deal with them. Feelings of loss. Feelings of isolation. Feelings of inadequacy. Feelings you have when you have to deal with something that others don’t. And you want to keep those feelings hidden because others don’t, won’t, or can’t understand.

Mulitple sclerosis.

Lupus.

Pancreatic cancer.

Alzheimer’s.

Breast cancer.

Lou Gehrig’s disease.

Prostate cancer.

Crohn’s disease.

Unless you have a condition like Parkinson’s disease or another chronic illness, you won’t, you don’t, and you can’t “get it.” You can’t understand. Not that you don’t want to, but you just can’t. Not fully, anyhow. It’s like eating ice cream. If you’re not the one licking the scoop on top of the cone, you really don’t know what it tastes like unless you’ve had it before.

You can sympathize, pity, encourage, and support, but you can’t understand. And so, some try to empathize, rationalize, apologize, and “humorize” the situation. But sometimes, there’s nothing to rationalize, no apology is needed, or it’s not funny. It just happens to be. There’s no reason one awakes day after day to face their foe in the mirror, nor is it anyone’s fault that they or a loved one suffers from a disease.

We can get frustrated and feel as if some people in our lives don’t get it. We reach the place where we don’t want to even mention PD because it is viewed as an excuse for pain, stiffness, memory loss, or any other ailment we might be experiencing at the time. Sometimes it seems that the reality of our disease, which is ever-present within our bodies, has disappeared from sight to the outer world. Yet, we know it is there as it hides within and can definitely be felt moment by moment.

As recipients of a disease or illness, we try — when our bodies and energy levels permit — to do what we are able, such as gardening, writing, working on cars, playing games, or socializing. We have a new vision for the short time we are allotted here on earth and strive to make the most of it. On some days, we feel we could climb a mountain (a little one), and on others, we know we can’t even walk to the base of a hill. It may even hurt to glance upward to look into the sky.

These are the days when sometimes others watch us, and I wonder if they think PD isn’t so bad. “Look at her,” they may say or think, “she’s digging up flowers! No one with a disability would have that much energy or strength.” I often don’t have the energy, just as others I know with PD don’t.

However, we push ourselves with the tasks we yearn to function in, and we finish because it feels good to be used, to be useful, to work, to move, to be needed. Yes, we push on even with the pain because, at least for me, the pain says, I’m alive, I can still do it. Today, anyhow. And yes, it also cautions me to take it a little easier, but not so easy that all that is left is to sit and watch life, instead of participating in it.

I may wish to hide what’s going on inside, but I’ve never been good at it. I wear a feeling of loss at times, because the fact is, I’ve lost something: control. And I wear a feeling of isolation, a feeling of being alone in the fight. I wear inadequacy by feeling that I can’t do, or can’t offer, what I used to. Everything’s just a little harder to accomplish.

But as hard as things may be at times in dealing with something others can’t understand, people mean well. Their intentions are honorable and they are trying to deal with this intruder from a different angle: It’s taken a part of the one they love, or it’s trying to.

So, I guess I’m thankful that sometimes I wear my heart on my sleeve because sometimes I don’t want to give this monster any more attention and talk about it. But sometimes I need to, and that’s when someone asks how it’s going. And if my answer is a little less than accurate, they glance at my heart laying there bare for all to see and reexamine my answer.

“You sure?” they ask after receiving a less than convincing “OK” response.

Fine. You’ve got me. I’ve got PD and, no, today I’m not OK. Today I just really need a friend.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease. 

https://parkinsonsnewstoday.com/2018/02/23/parkinsons-disease-wearing-your-heart-outside/

Simple Walking Test May Help Diagnose Dementia

NEUROSCIENCE NEWS  FEBRUARY 23, 2018
Source: AAN

Researchers report a simple walking test may help doctors to accurately diagnose the onset of dementia.

Researchers assessed participants’ manner of walking, or gait, by having all participants walk on a pressure-sensitive carpet that was 22 feet long. People were first asked to walk at three different speeds: slow, their preferred speed and as fast as possible. They were then asked to walk and count backwards at the same time and after that, to walk while carrying a tray. NeuroscienceNews.com image is in the public domain.

There’s a cause of dementia that can sometimes be reversed, but it’s often not diagnosed because the symptoms are so similar to those of other disorders. Now researchers say a simple walking test may be able to accurately diagnose the disease, according to a study published the February 21, 2018, online issue of Neurology.

The test involves seeing how fast a person can walk while doing something else at the same time, such as counting backwards or carrying a tray. The study found that the walking test may help differentiate whether someone has idiopathic normal pressure hydrocephalus or progressive supranuclear palsy.

Idiopathic normal pressure hydrocephalus (iNPH), caused by excess fluid in the brain, can often be reversed but it is usually not diagnosed because it shares symptoms like walking, balance and thinking problems with other neurologic conditions, primarily progressive supranuclear palsy (PSP), which is caused by damage to nerve cells in the brain. There is no cure for PSP, but treatment may help ease symptoms.

“It is important that people with idiopathic normal pressure hydrocephalus are accurately diagnosed so they can be treated, and their health can improve,” said study author Charlotte Selge, MD, of the Ludwig Maximilian University of Munich in Germany. “A simple walking test may help determine if a person has iNPH or PSP relatively early in the course of the disease. Our study found that adding another task while someone walks, and evaluating how it affects their walking ability, improves accuracy of the diagnosis.”

The study involved 27 people with iNPH, 38 people with PSP, and 38 healthy people of similar sex and age. Those with PSP and healthy controls had an average age of 69. Those with iNPH had an average age of 72. All participants received a complete neurologic exam, eye exam, MRI as well as thinking and memory tests. All were able to walk at least 30 feet without a walker or cane.

Researchers assessed participants’ manner of walking, or gait, by having all participants walk on a pressure-sensitive carpet that was 22 feet long. People were first asked to walk at three different speeds: slow, their preferred speed and as fast as possible. They were then asked to walk and count backwards at the same time and after that, to walk while carrying a tray.

Researchers found that walking while counting backwards resulted in a greater reduction of walking speed in those with PSP than in those with iNPH. Walking speed was reduced by 34 percent in those with PSP and by 17 percent in those with iNPH. When walking while carrying a tray, gait worsened for those with PSP but actually improved for those with iNPH, which may mean the dual-task test wasn’t challenging enough for those with iNPH, Selge said.

“People with PSP appear to be more sensitive to these dual-task walking tests than people with iNPH,” said Selge.

By just assessing walking, researchers were able to accurately diagnose who had PSP and who had iNPH 82 percent of the time. But when adding both dual-task tests to the assessment, diagnostic accuracy increased to 97 percent.

“Our findings suggest that adding these dual-task tests would be an inexpensive and effective way to improve diagnosis of iNPH,” said Selge. “Future studies may want to increase the complexity of tasks to see if they provide even more accuracy as well as insight into how the two diseases affect gait.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: The study was supported by the German Federal Ministry of Education and Research.

Source: Renee Tessman – AAN

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: The study will appear in Neurology.

http://neurosciencenews.com/dementia-walking-test-8549/

Glaucoma study finds brain fights to preserve vision

February 23, 2018 by Jessica Pasley, Vanderbilt University

Acute angle closure glaucoma of the right eye (intraocular pressure was 42 in the right eye). Credit: James Heilman, MD/Wikipedia

A team of researchers, led by David Calkins, Ph.D., vice chair and director of Research at the Vanderbilt Eye Institute, has made a breakthrough discovery in the field of glaucoma showing new hopes for treatments to preserve vision.

In addition, Calkins is encouraged that the findings released in the Proceedings of the National Academy of Sciences (PNAS) will have treatment ramifications to combat age-related neurodegenerative disorders like Alzheimer's and Parkinson's diseases.

The paper, "Axogenic Mechanism Enhances Retinal Ganglion Cell Excitability During Early Progression in Glaucoma," unmasked a revolutionary conclusion—in the past it was believed that as retinal activity is lost, the connection between the retina and the brain should be gone, but the opposite is true.

Calkins deemed the information one of the most significant discoveries since his team showed in 2010 that the first sign of injury in glaucoma occurs in the brain, and was similar to other age-related, central nervous system diseases.

"What we have demonstrated in our most recent study is that the brain fights back," said Calkins, Denis O'Day Professor of Ophthalmology and Visual Sciences and director of the Vanderbilt Vision Research Center. "And we identified the mechanism for what causes this compensatory response. We found that for a brief period of time this particular mechanism actually preserves vision, despite the onslaught of stress in glaucoma.

"This is a real paradigm shift," Calkins said. "The dogma has been that once started, neurodegenerative diseaseis a one-way path. But we found that individual neurons fight back to maintain signaling between brain regions, thereby slowing progression. It's a balance between disease and adaptation.

"We think we can develop new therapies based on this mechanism to keep the optic nerve signaling, which will maintain vision even as a disease progresses."

Diseases of the central nervous system involve early degradation of axon function that often precede degeneration—basically as the disease progresses, the retina stops talking to the brain, and soon afterward the axons begin to degenerate, then the retina and finally the brain, explained Calkins.

The team used a model of glaucoma, the leading cause of irreversible blindness in the world, to record and compare how the loss of synapses relates to the diminishment of signals to the axon.

Neurons have specialized projections called dendrites and axons. Dendrites bring information to the cell body and axons take information away from the cell body.

Information from one neuron flows to another neuron across a synapse.

In neurodegenerative disorders of the brain, those synapses are lost as the neuron dies.

Calkins' team found that the axon signals did not diminish, rather the signaling to the brain increased, meaning that neurons were fighting back against the loss of excitatory activity.

"We discovered a sodium channel that usually sits far away from the cell body of the neuron," Calkins said. "As the dendrites are lost, the sodium channel moves closer to the cell body and whatever residual activity remains, the channel boosts and amplifies the axon signal to the brain and for a brief period of time this mechanism actually preserves vision."

"With this information, we hope to bootstrap this natural adaptive mechanism and prolong signaling between brain regions and prevent subsequent degeneration. As long as signaling is maintained, progression slows and vision is maintained.

"Now that we have identified the mechanism that causes adaptation, we can exploit it through new drugs or even gene therapy."

More information: Michael L. Risner et al. Axogenic mechanism enhances retinal ganglion cell excitability during early progression in glaucoma, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1714888115 

Journal reference: Proceedings of the National Academy of Sciences

Provided by: Vanderbilt University

https://medicalxpress.com/news/2018-02-glaucoma-brain-vision.html

Deep Brain Stimulation Improves Some Parkinson’s Symptoms But at Risk of Greater Apathy, Study Shows

FEBRUARY 22, 2018   BY JOSE MARQUES LOPES, PHD

Deep brain stimulation (DBS) is effective in improving several neuropsychiatric symptoms of Parkinson’s disease, but can lead to increased apathy in patients, research based on an observational clinical trial in patients suggests.

The study, “Subthalamic stimulation and neuropsychiatric symptoms in Parkinson’s disease: results from a long-term follow-up cohort study,” appeared in the Journal of Neurology, Neurosurgery & Psychiatry.

Parkinson’s is caused by reduced levels of dopamine due to nerve cell death in a region of the brain called the substantia nigra, which controls the body’s balance and movement. The disease is characterized by various motor and neuropsychiatric symptoms.

Patients can develop neuropsychiatric symptoms as early as the premotor phase (before motor symptoms appear) until the late stages of the disease.

Dopamine treatment has been shown to have both positive and negative effects in Parkinson’s patients. Depending on the level of treatment, neuropsychiatric manifestations are divided into two main categories: “hypodopaminergic syndrome,” which involves apathy, depression, and anxiety; and “hyperdopaminergic syndrome,” which includes creativity, addictions to computer and gardening, impulse control disorders (ICDs), punding, and addiction to dopaminergic medications.

Deep brain stimulation is a surgical procedure that involves implanting a device to stimulate targeted regions of the brain with electrical impulses to treat neurological symptoms and help control movements.

Deep brain stimulation of the subthalamic nucleus (STN-DBS), the area of the brain that controls movement, effectively treats motor complications from levodopa (L-DOPA) therapy, but the procedure has also been linked to changes in some behavioral and neuropsychiatric symptoms. Apathy, potentially a sign of worsening cognitive function, is frequently reported in patients both shortly after surgery and during long-term follow-up.

Data on depression, suicide, and anxiety are more controversial, with some studies reporting no changes after deep brain stimulation, while others indicate either improvement or worsening. Studies on the influence on impulse control disorders also have contradictory results, but these reports did not compare STN-DBS treatment with a control group and patient follow-up was relatively short.

Researchers hypothesized that after STN-DBS, patients should show a decrease in impulse control disorders because the procedure reduces the requirement for dopaminergic medications, which have been linked to behavioral addictions.

The team conducted a long-term study (NCT01705418), at a single site in France, of neuropsychiatric symptoms in 69 Parkinson’s patients who had bilateral deep brain stimulation of the subthalamic nucleus. They were followed for a maximum of 10 years.

At a mean follow-up of six years, all impulse control disorders and dopaminergic addiction were significantly decreased, apart from eating behavior and hypersexuality. While the lack of improvement in excessive eating has been noted in previous studies and suggests different brain mechanisms, more research is needed to address the result in hypersexuality, the authors said.

Treatment also reduced neuropsychiatric fluctuations of euphoria and dysphoria (a state of generalized dissatisfaction, associated in this study with panic and distress), which researchers said was in line with previous studies that had shorter follow-ups.

However, the procedure also led to an increase in apathy, which researchers partly attribute to the lower levels of dopaminergic medications as well as their progressively reduced effectiveness. There was also an increasing trend in depression, which the team speculates could be attributed to insufficient dopaminergic stimulation as well as loss of autonomy associated with disease progression.

Subsequent retrospective analysis of 48 of the 69 patients revealed several temporary episodes of depression, apathy, anxiety, and impulse control disorders.

Seven patients developed dementia during follow-up, which the authors attributed to the natural course of the disease.

“The results show that STN-DBS was overall very effective in improving [ICDs] and neuropsychiatric fluctuations in parkinsonian patients in the long term despite a counteracting frequent apathy,” the investigators wrote.

“In the light of our data, we recommend to inform patients of the postoperative risk of apathy, depression and ICDs,” they said. Close follow-up of patients is mandatory to better manage neuropsychiatric symptoms, the researchers advised.

https://parkinsonsnewstoday.com/2018/02/22/deep-brain-stimulation-increases-apathy-parkinsons-disease-study/

Biomarker, clues to possible therapy found in novel childhood neurogenetic disease

 February 22, 2018,  Children's Hospital of Philadelphia

Researchers studying a rare genetic disorder that causes severe, progressive neurological problems in childhood have discovered insights into biological mechanisms that drive the disease, along with early clues that an amino acid supplement might offer a targeted therapy. The research, which found abnormalities in a biological waste-disposal process called autophagy, links the mechanism underlying rare pediatric neurogenetic disorders to more common neurodegenerative disorders, such as Huntington's or Parkinson's disease.

"We showed that this rare neurological disorder disrupts autophagy, which plays a role in many neurodegenerative disorders in both children and adults," said study leader Xilma R. Ortiz-Gonzalez, MD, PhD, a pediatric neurogeneticist at Children's Hospital of Philadelphia (CHOP). She added, "We identified a urine test that can serve as a biomarker of this specific pediatric disorder, which we call TBCK-encephaloneuropathy. We want to build a patient registry and eventually use this biomarker to test if it could help monitor response to treatment, with the long-term aim of developing a precision medicine treatment for this devastating disease."

The study team reported its findings online in Annals of Neurology on Dec. 29, 2017.

TBCK-encephaloneuropathy (TBCKE) is caused by a mutation in the TBCK gene, which has been a focus of previous research by CHOP scientists and others. Although >TBCK mutations have varied effects, including a broad range of intellectual disabilities, motor impairments, autistic features, and brain abnormalities, TBCKE is a severe subtype, with progressive neurodegeneration involving the brain as well as progressive muscle weakness.

The team also seeks to investigate why some children with TBCK mutations can have much milder presentations than others, and whether this provides a clue to understanding differences in the underlying mechanisms of the disease. The current study reported on a cohort of eight unrelated boys, ranging from age 9 to 14 years, all of Puerto Rican descent. All had a mutation, called the Boricua mutation, at the same location on the TBCK gene—p.R126X. They all share a very severe presentation, including profound intellectual disability (ID), epilepsy, low muscle tone, and progressive dysfunction in both the central and peripheral nervous systems. By adolescence, the patients had chronic respiratory failure caused by their progressive neuromuscular weakness.

Scientists already knew that the TBCK protein, coded for by the gene with the same name, regulates signals along the mTOR biological pathway. Abnormal mTOR signals occur in epilepsy, autism, ID and other neurological conditions. One key role for mTOR signaling is in autophagy, the normal cleanup process in which cells dispose of damaged proteins, lipids, and other biological objects.

When autophagy doesn't function normally, neurodegenerative diseases may result. Researchers in the current study found that the Boricua mutation leads to abnormal autophagy, which could be why this specific cohort of patients with TBCKE have a neurodegenerative course.

The study team found a potential biomarker for TBCKE—abnormal levels of chemicals called oligosaccharides in the patients' urine. Further studies will determine if oligosaccharide levels could become a simple laboratory test to help diagnose the disorder. Notably, oligosaccharide levels improved when the researchers added the amino acid leucine to the patients' cells in laboratory cultures.

"Leucine activates mTOR signaling that was disrupted by the mutation, so this finding suggests that leucine might offer some improvement in disease symptoms if used in patients," said Ortiz-Gonzalez. This is consistent with previous CHOP research in a TBCK-related disease, which showed potential therapeutic benefits in using leucine in affected cells.

Ortiz-Gonzalez and her CHOP collaborators are continuing to investigate the biology of TBCKE, while working to establish a patient registry of children with this rare disorder. Her eventual goal is to identify more patients and perform studies that could set the stage for a clinical trial to test leucine or a similar compound as a personalized treatment for this severe childhood disease.

More information: Xilma R. Ortiz-González et al, Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy, Annals of Neurology (2017).  DOI: 10.1002/ana.25130 

Journal reference: Annals of Neurology

Provided by: Children's Hospital of Philadelphia

https://medicalxpress.com/news/2018-02-biomarker-clues-therapy-childhood-neurogenetic.html

Shedding a tear may help diagnose Parkinson's disease

February 22, 2018   AMERICAN ACADEMY OF NEUROLOGY

MINNEAPOLIS - Tears may hold clues to whether someone has Parkinson's disease, according to a preliminary study released today that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to 27, 2018. 

"We believe our research is the first to show that tears may be a reliable, inexpensive and noninvasive biological marker of Parkinson's disease," said study author Mark Lew, MD, of the Keck School of Medicine of the University of Southern California in Los Angeles and a Fellow of the American Academy of Neurology. 

Lew says the research team investigated tears because they contain various proteins produced by the secretory cells of the tear gland, which is stimulated by nerves to secrete these proteins into tears. Because Parkinson's can affect nerve function outside of the brain, the research team hypothesized that any change in nerve function may be seen in the protein levels in tears.

For the study, tear samples from 55 people with Parkinson's were compared to tear samples from 27 people who did not have Parkinson's but who were the same age and gender. Tears were analyzed for the levels of four proteins. 

Researchers found differences in the levels of a particular protein, alpha-synuclein, in the tears of people with Parkinson's compared to controls. Additionally, levels of another form of alpha-synuclein, oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson's, were also significantly different compared to controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears. 

Total levels of alpha-synuclein were decreased in people with Parkinson's, with an average of 423 picograms of that protein per milligram (pg/mg) compared to 704 pg/mg in people without Parkinson's. But levels of oligomeric alpha-synuclein were increased in people with Parkinson's, with an average of 1.45 nanograms per milligram of tear protein (ng/mg) compared to 0.27 ng/mg in people without the disease. A picogram is 1,000 times smaller than a nanogram.

"Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson's disease and those who don't in a noninvasive manner is exciting," said Lew. "And because the Parkinson's disease process can begin years or decades before symptoms appear, a biological marker like this could be useful in diagnosing, or even treating, the disease earlier." 

More research now needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest stages of the disease, before symptoms start.

###

Register now for the 2018 AAN Annual Meeting Press Room in Los Angeles, April 21-27, 2018

The study was supported by The Michael J. Fox Foundation for Parkinson's Research and the Plotkin Foundation.

Learn more about Parkinson's disease at http://www.aan.com/patients.

The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with over 34,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, concussion, Parkinson's disease and epilepsy.

For more information about the American Academy of Neurology, visit http://www.aan.comor find us on Facebook, Twitter, Google+, LinkedIn and YouTube.

Media Contacts:

Renee Tessman, rtessman@aan.com, (612) 928-6137

Michelle Uher, muher@aan.com, (612) 928-6120

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

https://www.eurekalert.org/pub_releases/2018-02/aaon-sat022118.php

Testing tears could lead to cheap and effective Parkinson's disease screening

• Alex Matthews-King Health Correspondent  - 22 February 2018 

Parkinson’s patients’ tears had more than five times the level of abnormal molecule which forms nerve damaging clumps

A few shed tears could open up a cheap way to screen patients for Parkinson’s disease, allowing earlier diagnosis and, potentially, treatment that can delay the disease.

Researchers analysing the tears of Parkinson’s patients and non-affected adults found that patients with the disease had five times the level of alpha-synuclein, the protein molecule that forms toxic clumps and causes nerve damage, than the healthy patients.

“We believe our research is the first to show that tears may be a reliable, inexpensive and non-invasive biological marker of Parkinson’s disease,” said the study’s author, Dr Mark Lew, from the Keck School of Medicine at the University of Southern California.

“And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biological marker like this could be useful in diagnosing, or even treating, the disease earlier.”

The findings from an early human trial were presented at a conference of the American Academy of Neurology today.

Because Parkinson’s affects nerve signals around the body and not just in the brain, Dr Lew’s team predicted that the abnormal protein molecules linked with it’s progression would be found outside the brain as well.

The researchers recruited 55 people with Parkinson’s, and 27 people from a similar mix of ages and genders without the disease, and compared tear samples for differing levels of the protein.

They found levels of alpha-synuclein in a healthy, non-clumped form were lower in Parkinson’s patients’ tears.

However, they had significantly higher levels of the unhealthy form of the molecule, oligomeric alpha-synuclein – 1.45 nanograms per milligram of tear proteins, compared to 0.27 nanograms in healthy patients.

These abnormal protein clumps interfere with nerve signals and are a key factor in the nerve damage that marks out the progression of Parkinson’s disease.

“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who don’t in a non-invasive manner is exciting,” said Dr Lew.

Detecting Parkinson’s disease from bodily secretions isn’t entirely new.

Manchester academics are studying retired nurse Joy Milne’s peculiar ability to smell Parkinson’s and identify sufferers with remarkable accuracy.

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Team identifies genetic defect that may cause rare movement disorder

February 22, 2018, Massachusetts General Hospital

A Massachusetts General Hospital (MGH)-led research team has found that a defect in transcription of the TAF1 gene may be the cause of X-linked dystonia parkinsonism (XDP), a rare and severe neurodegenerative disease. The study, published in the February 22 issue of Cell, is a collaboration between the laboratories of Michael Talkowski, PhD, and Cristopher Bragg, PhD, both of the MGH Department of Neurology and the Collaborative Center for X-linked Dystonia Parkinsonism (CCXDP).

"Even though the first clinical descriptions of this disease were published more than 40 years ago, it has been difficult to determine its cause or what might be done to treat it," says Talkowski, who is also a member of the MGH Center for Genomic Medicine. "Perhaps the biggest challenge with XDP has been understanding its genetic basis, and without knowing the causative gene defect, it has been hard to hypothesize about the underlying disease mechanisms."

Occurring only among individuals with ancestry from the Philippines island of Panay, XDP causes the death of certain cells within the brain. Symptoms begin around age 40 with dystonia - involuntary muscle contractions that can force the body into abnormal, sometimes twisted positions - and eventually proceed to Parkinson's-like symptoms, such as slowness of movement and a shuffling gait. Patients become progressively more disabled as the disease progresses and often die from complications such as infections or pneumonia.

Prior to this study, it had been reported that all individuals with XDP share seven DNA sequence changes, which cluster within a region of the X-chromosome that includes the TAF1 gene. Bragg explains, "These sequence changes have always appeared to be inherited together; in other words, all reported patients had all seven sequence variants, and none have ever been found in unaffected people. Because of this pattern, it had not been possible to determine which, if any, of these changes may be pathogenic."

To address that question, Talkowski and Bragg worked with CCXDP Director, Nutan Sharma, MD, PhD, to mount the largest genomics study ever performed for XDP, analyzing a total of 792 DNA samples from individuals with XDP and their unaffected relatives, as well as historical samples from studies dating back to the initial descriptions of the disease. The analysis of these samples revealed a far greater genetic diversity among XDP patients than was previously known. While most shared a total of 54 unique sequence changes in a collection of variants known as a haplotype, in some individuals the haplotype had been broken apart due to genetic recombination. By comparing these recombination events, it was possible to narrow the disease-causing genomic segment to a smaller region that contained only the TAF1 gene.

To further pinpoint any altered functions associated with these variants, the Bragg laboratory reprogramed skin cells from patients with XDP and their healthy relatives back into stem cells, which differentiated into neural progenitor cells and then mature neurons. Talkowski's team used RNA sequencing to characterize TAF1 expression patterns and found a defect in how the DNA sequence is transcribed into RNA in neural cells from XDP patients. In those cells, a portion of the TAF1 RNA appeared to terminate prematurely, which reduced expression of the full-length RNA. The truncated TAF1 RNA ended close to a known XDP-specific sequence variants - a large DNA insertion known as a retrotransposon. To determine whether the retrotransposon caused the transcriptional defect, the Bragg lab used genome editing tools to remove the sequence, which restored RNA transcription and normalized TAF1 expression.

In a separate study published last December in PNAS, Bragg and colleague, Laurie Ozelius, PhD, also of MGH Neurology, had analyzed the sequence of the retrotransposon in patients with XDP and found that it contained a segment of repetitive DNA that was longer in patients who developed symptoms at an earlier age and shorter in those whose symptoms appeared later. Bragg says, "The combined results of these two studies provide the strongest evidence to date that this retrotransposon is the most likely cause of XDP."

Talkowski adds, "We cannot say definitively that this mechanism is the sole cause of XDP. There is still much work to do. However, it is a major step forward in understanding the defects that occur in patients' cells, and the integrated genomic approaches we have used might be applicable to other unsolved disorders. This finding in XDP is particularly exciting given the tremendous advances that have occurred in recent years with RNA-based therapeutics. The possibility that XDP may result from defective transcription means there may be ways to treat it, and that is certainly cause for hope."

More information: Cell (2018). DOI: 10.1016/j.cell.2018.02.011 

Journal reference: Proceedings of the National Academy of Sciences

Provided by: Massachusetts General Hospital 

https://medicalxpress.com/news/2018-02-team-genetic-defect-rare-movement.html