ULTRASOUND ELASTOGRAPHY NEW MEANS OF ASSESSING RIGIDITY IN PARKINSON'S DISEASE

20th July 2016 

Ultrasound elastography is a means of assessing the mechanical properties of tissue, by applying stress and detecting tissue displacement using ultrasound. It provides information on tissue stiffness. 

Ultrasound shear wave elastography has been used to assess muscle stiffness in people with Parkinson's Disease. The assessments were made by assessing the biceps of people with Parkinson's Disease. 

Ultrasound shear wave elastography of the longitudinal biceps brachii was performed on 46 people with Parkinson's Disease and 31 healthy controls The mean Young's modulus was 59 kPa in remarkably symptomatic arms, 47 kPa in mildly symptomatic arms, and 24 kPa in healthy controls. A significant difference was found between healthy controls and all people with Parkinson's Disease.

The distinctiveness of the results enable Ultrasound shear wave elastography to be used as a quantitative assessment of muscle stiffness in people with Parkinson's Disease.

Reference : Clinical Imaging [2016] 40 (6) : 1075-1080 (L.J.Du, W.He, L.G. Cheng, S.Li, Y.S.Pan, J.Gao) Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/27408992

http://www.viartis.net/parkinsons.disease/news/160720.pdf mail@viartis.net
©2016 Viartis 

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Ultrasound (Shear wave elastography)

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Shear wave elastography

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Propagation mapping

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The principle behind shear wave elastography

Shear waves are generated inside the human body by means of an ultrasonic burst (left). Depending on tissue stiffness, shear waves travel at varying speed, but generally very slowly through the human body. Their propagation can be followed and visualized using conventional ultrasound imaging techniques (right). The propagation speed of the shear waves directly correlates with tissue stiffness

Video:

http://www.toshibamedicalsystems.com/products/us/aplio_shear.html

New Findings Challenge Current View on Origins of Parkinson’s Disease with Videeo

July 22, 2016University of Leicester

The neurodegeneration that occurs in Parkinson’s disease is a result of stress on the endoplasmic reticulum in the cell rather than failure of the mitochondria as previously thought, according to a study in fruit flies. It was found that the death of neurons associated with the disease was prevented when chemicals that block the effects of endoplasmic reticulum stress were used.

Some inherited forms of early-onset Parkinson’s disease have typically been blamed on poorly functioning mitochondria, the powerhouses of cells. Without reliable sources of energy, neurons wither and die. This may not be the complete picture of what is happening within cells affected by Parkinson’s. Researchers from the MRC Toxicology Unit at the University of Leicester used a common fruit fly to investigate this further; fruit flies were used because they provide a good genetic model for humans.

Studies on human subjects are of limited use for elucidating the signaling pathways and cellular processes underlying the neurodegenerative process. This is because both ethical and technical constraints limit the extent to which genetic analysis can be performed in humans.

Flies are a well-established model animal to understand the molecular mechanisms of human diseases. This is because about 75% of human disease-causing genes are found in the fly in a similar form. Also, they are easy to work with, breed quickly and many tools are available to manipulate any genes in the fly. In flies, potential therapeutic drugs can be mixed with food and readily tested.

It was found that the bulk of the damage to neurons with damaged mitochondria stems from a related but different source - the neighbouring maze-like endoplasmic reticulum (ER).

The ER has the important job of folding proteins so that they can do the vast majority of work within cells. Misfolded proteins are recognized by the cell as being dangerous. Cells halt protein production if there are too many of these harmful proteins present. While this system is protective, it also stalls the manufacture of vital proteins, and this eventually results in the death of neurons.

To find out if ER stress might be at play in Parkinson’s, a team led by Dr Miguel Martins analyzed fruit flies with mutant forms of the pink1 or parkin genes. Mutant forms of pink1 and parkin are already known to starve neurons from energy by preventing the disposal of defective mitochondria. These genes are also mutated in humans and result in hereditary versions of the disease. Much like Parkinson’s patients, flies with either mutation move more slowly and have weakened muscles. The insects struggle to fly and they lose dopaminergic neurons in their brains – a classic feature of Parkinson’s.

Compared to normal flies, Miguel’s team found that the mutants experienced large amounts of ER stress. The mutant flies did not manufacture proteins as quickly as the non-mutants. They also had elevated levels of the protein-folding molecule BiP, a telltale sign of stress.

One function of pink1 and parkin genes is to help degrade mitofusin - a protein that tethers the endoplasmic reticulum to mitochondria. Mutant flies have an abundance of this protein. It was found that the mutants had more of their mitochondria attached to the ER than normal flies. For this reason, the researchers suggest that ER stress is related to extra tethering of mitochondria, thereby preventing the removal of defective versions of the organelle.

Mutant flies, which have more of these tethers, have fewer dopaminergic neurons, which can have an adverse effect on the brain. By reducing the number of these tethers it is possible to prevent the loss of the neurons. When the researchers experimentally lowered the amount of mitofusin in the mutants, the number of tethers fell and the neuron number increased again (see figure). The flies’ muscles also remained healthy despite the mitochondria themselves still being defective.

These results suggest that the neurodegeneration seen in Parkinson’s is a result of ER stress rather than a general failure of the mitochondria. The scientists were able to prevent neurodegeneration in mutant flies not only by reducing mitofusin, but also with chemicals that block the effects of ER stress.

Dr Miguel Martins said: “This research challenges the current held belief the Parkinson’s disease is a result of malfunctioning mitochondria. By identifying and preventing ER stress in a model of the disease it was possible for us to prevent neurodegeneration. Lab experiments, like this, allow us to see what effect ER stress has on Parkinson’s disease. While the finding so far only applies to fruit flies, we believe further research could find that a similar intervention in people might help treat certain forms of Parkinson’s.”

The research has been published in the journal Cell Death and Disease and a video explaining the main findings can be found here 

https://www.youtube.com/watch?v=13oA5eiH-8s  (video will be made public after embargo lifts)

http://www.labbulletin.com/articles/New-Findings-Challenge-Current-View-Origins-Parkinson-Disease#.V5PKv1e1WoM

Most accurate map of the human cortex unveiled

By Tim NewmanJuly 23, 2016

The most complete map of the cerebral cortex ever to be charted has been unveiled this week in Nature. No less than 97, distinct, previously undescribed regions have been found.

A map showing some of the 180 cortical regions.

Image credit: Matthew Glasser, Ph.D., David Van Essen, Ph.D., Washington University

The cerebral cortex - the outer portion of the mammalian brain - is a 2-4-millimeter thick layer of gray matter.

This densely folded formation of cells is heavily involved in a number of tasks, including attention, memory, perception, consciousness, awareness, thought, and language.

Over the last century, neuroscientists have divided the cortex into ever smaller sections of discrete functionality. 

Although the brain is known to function, very much, as a whole, dividing it into bite size chunks helps understand how it can create such complex activity.

Breaking research provides us with the most complex map of the cerebral cortex to date.

Early studies of the cortex and attempts to understand its organization have relied on single measures - for instance, examining cell types in postmortem brains.

Although these studies have allowed scientists to describe distinct areas, the accuracy has been called into question, and the ability to compare structures between brains has been lacking. 

Software, scans, and brain maps

Scientists, funded by the National Institutes of Health through its Human Connectome Project (HCP), set out to bring these blurred images of the brain into much sharper focus.

To develop a more detailed picture of cortical regions, they used a number of cutting-edge techniques and overlaid them.

The work was carried out by David Van Essen, Ph.D., and Matthew Glasser, Ph.D., of Washington University in St. Louis, MO, and their colleagues.

The researchers developed software capable of mapping areas of the brain by collating data from a large number of noninvasive but precisely aligned magnetic resonance imaging (MRI) brain scans. 

In all, they used scans from 210 healthy participants. The imaging technology charted cortical architecture and its activity, connectivity, and topography. Measures included cortex myelin content - a fatty component important for signal transduction - and the thickness of the cortex. Additionally, functional MRI (fMRI) scans were taken both during tasks and while at rest.

Dividing the mind

Glasser and his team looked for areas of the cortex where two or more properties changed; these became the borders on the map. He says: "If you crawl along the cortical surface, at some point you are going to get to a location where the properties start changing, and where multiple independent properties change in the same place."

The best map of the cortex prior to this advance described 83 areas, all of which were reconfirmed by the new methodology, with the addition of 97 areas that are entirely new to science. 

Each of the 97 new regions contains cells with similar connectivity, structure, and function that differs from their neighbors.

The findings were then double checked using another sample of 210 healthy participants. When running the software on fresh brains, some of the cortical regions were found to be in slightly different positions or of subtly different sizes in some individuals. However, the software was still capable of successfully adjusting for these changes and mapped them accurately.

"The ability to discriminate individual differences in the location, size, and topology of cortical areas from differences in their activity or connectivity should facilitate understanding of how each property is related to behavior and genetic underpinnings."

Matthew Glasser, Ph.D.

The map has the potential to answer, or at least help answer, some of the more esoteric questions neuroscience has to offer about interpersonal differences; questions relating to interpersonal differences, and intellectual and creative abilities, for instance.

Below is a short video, produced by Nature, which briefly explains the new findings:

The future of brain maps

Nothing is perfect, of course, and the map does have certain limitations. As an example, it has little to say about the biochemical activity of the brain, or the activity of individual neurons within these newly defined areas.

Rex Jung, a neuropsychologist at the University of New Mexico in Albuquerque, spoke to Nature about the cortical map, He says: "It is analogous to having a fantastic Google Earth map of your neighborhood, down to your individual backyard. Yet, you cannot really see how your neighbors are moving around, where they are going, or what sort of jobs they have."

Shortfalls aside, the new map and the associated software is certainly a huge leap forward. Glasser does not plan on stopping here, either. He says: "We're thinking of this as version 1.0. That doesn't mean it's the final version, but it's a far better map than the ones we've had before."

The researchers predict that as technology advances, each of the subdivisions so far identified will likely be split into ever smaller subsections as instrument sensitivity improves.

http://www.medicalnewstoday.com/articles/311847.php

DBS May Slow Cognitive Decline in Alzheimer's Disease

Fran Lowry

July 22, 2016
                                                    

A multicenter phase 2 study showed that some patients with mild Alzheimer's disease (AD) who received deep brain stimulation of the fornix (DBS-f) experienced an increase in cerebral glucose metabolism, and some patients experienced a slowing of cognitive decline.

These positive effects were seen only in patients aged 65 years and older, not in younger patients.

Nevertheless, the findings are encouraging, said lead researcher Andres Lozano, MD, PhD, professor and chairman, Department of Neurosurgery, University of Toronto, Canada.

"These findings indicate that we are headed in the right direction with our research on DBS as a treatment of Alzheimer's disease. In AD, certain areas of the brain shut down and no longer metabolize glucose to the normal level, and we hope that by stimulating the circuits in the brain that are involved, that we can restore function within the fornix and that that in turn will lead to improvement in the signs and symptoms of Alzheimer's," Dr Lozano told Medscape Medical News.

The study was published online July 18 in the Journal of Alzheimer's Disease.

Age a Predictor of Response?

Dr Lozano and his group conducted an earlier phase 1 study involving six patients with Alzheimer's disease. In that study, in some patients who received constant DBS to the fornix, which is a major fiber bundle in the brain's memory circuit, there was an increase in hippocampal volume after 1 year.

The current phase 2 study included 42 patients aged 45 to 85 years. Twelve patients were younger than 65 years; 30 were 65 years of age or older.

The patients had mild dementia with global Clinical Dementia Rating (CDR) scale scores of 0.5 or 1 and Alzheimer's Disease Assessment Scale–11 (ADAS-Cog 11) scores of 12 to 24 at baseline.

All patients were taking stable doses of donepezil (Aricept, Eisai Inc), galantamine (Razadyne, Janssen Pharmaceuticals, Inc), or rivastigmine (Exelon, Novartis Pharmaceutical Corporation) for at least 2 months prior to the start of the study.

The patients were implanted with DBS electrodes directed at the fornix. They were then were randomly assigned to receive either active or sham stimulation and were monitored for 12 months. Once follow-up was complete, the electrodes were turned on for all patients.

In addition to evaluating the safety of DBS-f, the investigators measured changes in cognitive function using the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Clinical Dementia Rating–Sum of Boxes (CDR-SB) scales at 6 and 12 months.

Secondary clinical outcomes at 6 and 12 months included the California Verbal Learning Test, Second Edition (CVLT-II), the Alzheimer's Disease Cooperative Study Activities of Daily Living scale (ACDS-ADL), and the Neuropsychiatric Inventory (NPI).

Changes in cerebral glucose metabolism were assessed with [¹⁸F]-2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET).

Overall, at 12 months, there was no significant difference between the patients who were receiving stimulation and those who were not. For both groups, changes in scores on the ADAS-Cog 13 and the CDR-SB were similar; both showed comparable declines. 

he same result was seen for the secondary clinical measures.

However, in a post hoc subgroup analysis, older patients appeared to derive some benefit from DBS, with those in the active, or "on," stimulation group showing less decline in both ADAS-Cog 13 and CDR-SB scores.

The difference in worsening of ADAS-Cog-13 scores in patients aged 65 years and older who received stimulation vs those who received no stimulation was 4.5 + 2.0 points at 9 months and 4.1 + 2.6 at 12 months.

A similar benefit was observed in the CDR-SB scores in older patients.

A similar trend for benefit for older patients was seen with regard to FDG-PET for glucose metabolism. Patients younger than 65 years showed a decrease in metabolism while both "on" and "off" stimulation, whereas patients aged 65 years and older showed increased metabolism while "on" stimulation that was 14% to 20% greater than that observed in the group as a whole at 6 and 12 months.

"This was an exploratory study, so we didn't have a fixed number of patients and a set hypothesis we were testing. It was to see whether there might be some patients who might respond," said Dr Lozano.

He explained how increasing glucose metabolism could be of benefit to patients with AD.

"These areas of the brain are underperforming. It's as if the lights are dim in some areas of the brain. They are shut down. We are trying to turn them back on. We think that the symptoms come because these circuits are underperforming, so we would like to boost the activity of these circuits using electricity to see if that, in turn, restores the cognitive function of patients," Dr Lozano said.

Interesting, Intriguing

Commenting on the findings for Medscape Medical News, Gregory A. Jicha, MD, PhD, professor of neurology, Alzheimer’s Disease Center, University of Kentucky, in Lexington, described the study as "interesting."

"I was exposed to it very early on in the development process, when [the investigators] were treating a woman for an overeating disorder, and as they were aiming for the part of the brain that controls appetite, they missed by a little bit and got close to the fornix, and what happened was her memory became close to photographic with the stimulator there.

"That really intrigued them and got them to think that the DBS stimulating that fornix is going to turn on the memory circuits that are turning down in Alzheimer's disease, in much the same way we use DBS to turn back on motor circuits that are shutting down in Parkinson's disease."

Dr Jicha noted that he found the FDG-PET data that show increased metabolic activity "intriguing."

"We know that the health of nerve cells is critically dependent on their activity, and the fact that they were able to show in the older subjects effects that persisted to 1 year is intriguing. That raises interest in determining how stimulating one area of the brain can have very distant effects on other areas of the brain, something that's not really been looked at in Parkinson's disease per se," he said.

The study raises important questions, Dr Jicha added.

"For one, why do the elderly appear to benefit while younger Alzheimer's disease patients do not appear to benefit from DBS? The researchers say they feel that the elderly may have a less aggressive form of disease. That still needs to be determined, especially since their study population was really a mild disease population.

"Also, there was a very small number of subjects. So is that finding a fluke? Is the negative effect seen in the younger folks a real effect or is the post hoc positive effect in the older individuals really what the effect will turn out to be when larger populations are studied?

"I think that they've raised some interesting points, but clearly we haven't definitively proven that deep brain stimulation either is beneficial or is not beneficial on the basis of the results of this study. We're left with that lingering question. This appears to be a safe way to approach the disease, but we always watch for post hoc analyses because the study was not designed for that."

The study was supported by the National Institute on Aging, the Federal Economic Development Agency for Southern Ontario, and Functional Neuromodulation Ltd. The authors' financial relationships with industry are listed in the original article. Dr Jicha has disclosed no relevant financial relationships.

http://www.medscape.com/viewarticle/866489?src=wnl_edit_tpal#vp_1

Longford woman Adell raises funds for Parkinson's

July 23, 2016

On the June bank holiday, seventeen ladies set off from various locations to support Adell Carberry Dunleavy and the Parkinson’s Association of Ireland by taking part in the VHI Ladies Mini Marathon in Dublin.

 The group was made up of some of Adell’s closest friends, work colleagues, her two daughters, and some of their friends from college.

Adell was diagnosed last August with early-onset Parkinson’s disease and says she has received huge support from friends. She told the Leader: “That is why I decided that I wanted to give back and return the generosity others have shown to me.”

The group raised an impressive €2,245 but most of all, it was a fantastic day full of laughter and  positivity.

http://www.longfordleader.ie/news/news/211810/longford-woman-adell-raises-funds-for-parkinson-s.html

Boxing training used to fight against Parkinson's disease

July 23, 2016

Boxing class giving students upper hand in quality of life

Kris Cameron leads a boxing class for people with Parkinson’s disease at TITLE Boxing Club in Cedar Rapids on Thursday, July 14, 2016. (Adam Wesley/The Gazette)

CEDAR RAPIDS — Members of Kris Cameron’s boxing class aren’t fighting each other. They’re fighting Parkinson’s disease. And they’re winning the battle to increase their strength and dexterity.

When Christina Larsen, 46, of Cedar Rapids, stepped into her first boxing class in April, she left in tears. She had spent so much time and energy trying to hide her young-onset Parkinson’s that her right side was weak and slow to react to her movement impulses.

“It was like I’d had a stroke,” she said.

Four months later, she’s landing rapid jabs with both hands on the heavy bags at TITLE Boxing in Cedar Rapids.

“Now I’m boxing the crap out of it,” she exclaimed. “Isn’t it awesome?”

Diagnosed in 2009 at age 38, she decided to check out boxing as a way to increase strength and coordination after seeing a news report last spring. She was intrigued to learn that adding boxing to a patient’s arsenal of exercises seems to help counter the progressive nervous system disorder that most commonly affects muscles, movement and balance.

Using air quotes, Larsen said she joined a “normal” boxing class at the northeast-side facility, where she was greeted with open arms by staff and students. She’s worked her way up to five classes a week, adding Cameron’s Thursday afternoon class geared specifically for people with Parkinson’s disease.

“Three months ago, I couldn’t button my shirt,” said Richard Wolfe, 69, of Cedar Rapids. “A month ago I couldn’t touch my hands on the floor and keep my knees straight. Now I can do both.”

He was diagnosed with Parkinson’s disease about eight years ago. He’s been exercising with Cameron for five months and took up boxing about three and a half months ago. He also takes dance lessons. “The choreography helps with mind coordination,” he said.

Wolfe has participated in a couple of exercise studies at the University of Iowa, including a walking study, but when winter came and he had to move indoors, he grew bored and quit.

He’s no longer bored.

“When boxing started, I found muscles I hadn’t used in years,” he said.

Mike Van Horn, 66, of Cedar Rapids, was diagnosed with Parkinson’s disease three years ago. He has been exercising with Cameron for more than two years and added boxing in November. During a recent session, he quickly showed off the newfound spring in his step — being able to hop on both feet and add a midair shift from right foot forward to left foot forward.

“You can see the stuff I can do now, that I couldn’t do before,” he said with pride. “I’m moving so much better.”

It’s easier to get up in the morning and move around in his everyday life, he noted. And yet, he’s not wearing blinders.

“We know that this is a progressive disease and we’re going to get worse as time goes on, unfortunately,” Van Horn said, “but we try to delay it.”

Improvements like he and his classmates are experiencing give them hope, Van Horn said.

“The only thing we’ve got is hope,” he said. “I check the Internet almost every morning to see (if) maybe there’s a cure. You’d know about it, if there’s a cure. It’d be a big thing and make headlines in the news. But you just keep looking anyway.”

And exercising.

INSTRUCTOR

Cameron, 46, of Cedar Rapids, has been a personal trainer in the Corridor for 20 years. She’s certified in nearly 20 specialties, from arthritis and osteoporosis programs to the science of bodybuilding and cardiovascular nutrition and fitness. She works with all ages, but spends most of her time focused on the elderly and people with movement challenges and chronic conditions.

Her passion for Parkinson’s patients grew out of watching her father become inactive after his diagnosis, then quickly deteriorate and succumb to the illness. About six years ago, she started researching the disease and discovered that exercise can help delay its progression in some cases.

“The more I read, the more I was intrigued,” she said. She sought out a certification program and now teaches seven or eight classes a week for people with Parkinson’s, at sites in Cedar Rapids, Coralville, Iowa City and Williamsburg.

“It’s very much a needed service,” she added.

Last fall, she saw a “60 Minutes” segment on the Rock Steady boxing program for people with Parkinson’s.

“All of a sudden, the interest in boxing just really blew up,” she said. Already certified in kickboxing, she sought out further training and began offering her own class, which also folds in functional exercise.

“It’s not just an hour of boxing. We also work on a lot of strength and balance and gait — some of the same things we work on in the other (exercise) class, but then we have that other component of the boxing, which is a little more challenging for people who are up for that kind of a challenge,” she said.

During a recent Thursday afternoon session, four women and six men middle-aged and older had their hands taped up, then hit the gym running laps, before moving to the floor for squats, head turns, arm turns mimicking flipping flapjacks, footwork, pivots and jabs in the air. Next, they pulled on the gloves and began punching the long heavy bags suspended from the ceiling in nine neat rows.

Cameron moved among her students, guiding movements, correcting form and offering words of encouragement and assurance as they moved through a series of arm and foot work.

“You have a lot of power in that right cross,” she told Larsen.

“It’s a lot like dancing, with arm movement, foot movement and balance,” she told the class. “It’s more than just punching. You’ll apply that the more that you do it.”

After several rounds at the bags, her students moved back to the floor for cool down and coordination exercises — and plenty of stretching.

“I’m proud of all of you for just coming in and trying something different,” she said. “You get kudos for that.”

They’re about halfway through Cameron’s first 12-week boxing session. Since she is collecting data from the class and its students, tuition is free. Her work is being sponsored by the Iowa chapter of the American Parkinson’s Disease Association.

“This isn’t something that’s going to be a major public study,” she said, but the results will help guide her further efforts to improve the lives of people with Parkinson’s disease.

The benefits are reciprocal.

“These are the best people I’ve ever met,” she said. “We all have those days where we really don’t want to leave the house or get out of bed, and I look at these people who are having difficulty with the simplest things like walking and getting up out of a chair, and they’re coming to every class and they’re working hard on all these things — and they have a great attitude about it. I just see the hope that these people still have. Even though they are faced with an incurable disease, they have a lot of hope,” she said.

“If something as simple as exercise can help, I’m there.”

Video:

http://www.thegazette.com/subject/news/health/boxing-training-used-to-fight-against-parkinsons-disease-20160722