Dover Pops concert benefits Greg Rice Foundation

April 29, 2017  by Linda Klein Means

Thus “Dover Pops! Classical Meets Jazz,” a fundraising concert sponsored by the foundation, is back for a second year.

Out of tragedy, sometimes, comes opportunity and unexpected gifts. Such is the case with Dover’s Greg Rice, who was diagnosed with Parkinson’s disease in 1993. As symptoms progressed and he became unable to work, he discovered a previously unknown talent for composing classical music, and has, since 2003, composed more than 70 works, and been featured on ABC “Prime Time Live,” two NECN features, and a BBC documentary the brain and creativity.

And he has developed a passion for helping others and for seeking ways to remove the scourge of Parkinson’s and related neurological diseases. Thus he founded the Greg Rice Foundation, which raises money for research into a cure as well as funding organizations that make the lives of sufferers easier.

Thus “Dover Pops! Classical Meets Jazz,” a fundraising concert sponsored by the foundation, is back for a second year. On Friday, May 5, the public is invited to the Dover Church at 6:30 p.m. in Kraft Hall for cocktails and hors d’eourves prior to the 7:30- 8:30 p.m. concert in the sanctuary. Get your tickets, at $30 apiece, by calling 774-893-4022, or by going to www.doverpops2017, or at the door.

Last year’s event was a sellout, so act soon.

The evening will provide a rare mix of musical styles, with something for everyone. Joe Reid will play jazz piano, Stacia Kraft will sing torch songs, a quartet from the Wellesley Symphony Orchestra will play classical selections, and Sam Draper will play jazz violin.

The Greg Rice Foundation is a charitable, tax-exempt, 501(c)(3) organization, dedicated to raising awareness and research dollars to find a cure for Parkinson’s disease.

The foundation:

1. Contributes money to medical and research institutions dedicated to finding a cure for Parkinson’s disease.2. Raises awareness and money to cure Parkinson’s disease, primarily through the arts.

3. Sponsors fundraising events with performers and artists.

4. Emphasizes the power of people to overcome their physical and medical challenges and demonstrates how courage and determination can result in amazing achievements.

For more information, please visit www.gregricefoundation.org.

Greg Rice with his children

http://provincetown.wickedlocal.com/news/20170429/dover-pops-concert-benefits-greg-rice-foundation

Favorite Moments from the 2017 Parkinson's Unity Walk #PUW2017

April 28, 2017

https://youtu.be/Pvu83EWr7sc

Thank you for walking together with us! This video is brought to you courtesy of ACADIA Pharmaceuticals.  

Favorite Walk Moments from the 2017 Parkinson’s Unity Walk, held on Saturday, April 22, 2017 in New York City’s Central Park. Includes moments shared by participants and supporters using the event hashtag: #PUW2017.

Support the 2017 Parkinson’s Unity Walk by making a donation at www.UnityWalk.org by Monday, June 5, 2017.  

100% of donations go to Parkinson's research funded by six major U.S. Parkinson's foundations: American Parkinson Disease Association; National Parkinson Foundation and Parkinson's Disease Foundation (divisions of the Parkinson's Foundation); The Michael J. Fox Foundation for Parkinson's Research; The Parkinson Alliance; and The Parkinson's Institute and Clinical Center. 

Music Credit:

Megatrax collection, Disc# MX300, Track #2, "Don't You Wanna"

Track is licensed to the Parkinson's Unity Walk for "Syndicated Internet" production though ASCAP & BMI

https://www.youtube.com/watch?feature=youtu.be&v=Pvu83EWr7sc

Doctor and patient running miniMarathon together

April 28, 2017

To watch video:
http://www.whas11.com/news/local/doctor-and-patient-running-minimarathon-together/435048984

LOUISVILLE, Ky. (WHAS11) -- The bond for this doctor and patient goes miles outside Norton Hospital.

"When I met  Dr. Al, he said that he was thinking about running the marathon in Louisville, and I said, ‘well how far have you run?’ and he said, ‘well so far 13 miles,’ and I looked at my wife and thought, oh boy is he in for a struggle. After that, we just, we said, ‘let’s start running together,’" said Bill Reed.

Parkinson's patient, Bill Reed, and his neurologist Dr. Mohammad Alsorogi, who Reed calls "Dr. Al" quickly became running buddies and training partners after Reed was diagnosed over 5 years ago.

"Not really training together he was more like my trainer, but it was very interesting since that time," said Dr. Mohammad Alsorogi.

If you ask Dr. Alsorogi, he has learned a lot from lifelong marathoner Bill Reed.

"Bill helped me finish, the Chicago marathon really. I don’t think I would be able to finish it without his instructions and inspiring words," said Dr. Mohammad Alsorogi. "I mean we never run out of topics when we run so we keep talking for whatever, run 2 hours, 3 hours, 4 hours. We keep talking which is really interesting and entertaining."

Reed and Dr. Al will run the miniMarathon together. Last year, they ran together for 8 miles, then Dr. Alsorogi ran the mini. Reed ran the full—his 50th marathon. That was his 10th since being diagnosed with Parkinson's.

"This year we are going to run the mini together and probably stop, maybe have a beer on the way, and enjoy ourselves this year," said Reed.

Reed says he knew his Parkinson's diagnosis would impact his passion of running. He is a little slower now but he loves it just as much.

"It just changed my perspective in a good way. When I used to train, I used to say, man, I've got to run a 10 miler this week. Now I say, I get to run a 10 miler this week because a lot of people are not fortunate with Parkinson's to be able to run and be able to do the things that I do," said Reed. 

© 2017 WHAS-TV

http://www.whas11.com/news/local/doctor-and-patient-running-minimarathon-together/435048984

Rumblings of Parkinson’s: Gut Microbiome Shifts in Early Stage of Disease

April 28, 2017

Microbial Shift. 

The composition of bacterial species in the gut, shown here at the genus level, reorients in the early stages of Parkinson’s disease. [Image courtesy of Bedarf et al., Genome Science, 2017].

By the time a person with Parkinson’s notices something is wrong, the microbes in his gut may have long known about it. Reporting April 28 in Genome Medicine, researchers led by Ullrich Wüllner of the University of Bonn in Germany describe striking changes in the microbial communities living in the intestines of people in the earliest stages of the disease. Based on specific shifts of microbial species in the PD gut, the researchers speculated that the microbiome could interfere with the production of short chain fatty acids, or the permeability of the mucosal gut barrier—two functions intimately linked with inflammation and potentially with neurodegeneration.

“[This study] adds to the considerable evidence that the microbiota are involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerations,” commented Robert Friedland of the University of Kentucky in Louisville, who was not involved in the work. “Their data clarify with greater detail than previously available the nature of bacterial populations in the colonic lumen in PD.”

The study is the latest in steady stream of papers describing an altered microbiome in people with PD (see Keshavarzian et al., 2015, Scheperjans et al., 2015, Unger et al., 2016). Whether these microbial changes are a cause or consequence of the disease process is unclear, although a study in mice colonized with human microbes suggested both may be true: PD somehow alters the composition of the intestinal flora, which in turn accelerates pathology (see Dec 2016 news).

Co-first authors Janis Bedarf in Bonn and Falk Hildebrand at the European Molecular Biology Laboratory in Heidelberg wanted to measure microbiome changes in the earliest stages of the disease, within one year of diagnosis and prior to starting dopaminergic therapy. L-dopa is known to cause constipation, Wüllner told Alzforum, hence might interfere with intestinal flora. The researchers also used next-generation sequencing to survey the entire microbiome, rather than sequencing only 16S rRNA as prior studies had done. This more comprehensive “metagenomics” approach allows quantification of microbial inhabitants down to the species level, and also accounts for bugs such as viruses and fungi.

The researchers compared the gut metagenomes taken from stool samples of 31 early PD patients to 28 healthy age-matched controls. To avoid effects of sex, they only included men in the study. The investigators observed significant differences between the two groups. In particular, they found increases in the Firmicutes family, in unclassified bacteria, and in the genus Akkermansia, and found decreases in Prevotella and Eubacterium genera in PD patients relative to controls. At the species level, men with PD had an overabundance of Akkermansia muciniphila and Alistipes shahii, and fewer Prevotella copri, Eubacterium biforme, and Clostridium saccharolyticum. The overall diversity of bacteria was the same between the groups. Notably, PD patients had fewer gut viruses, including bacterial and archaeal phages. Based on the abundance of six different bacterial taxa, the researchers could correctly identify 84 percent of the PD patients.

The researchers found no correlation between the microbiome and the severity of motor symptoms, or constipation. They expected this, given the early disease stage and few reported bowel problems among the participants. While not on L-dopa, some of the patients were taking other medications. The researchers found that people taking both MAO inhibitors and amantadine had greater diversity of microbial species, while those taking statins had alterations in five families of bacteria. However, these differences did not contribute to those observed between PD patients and controls. 

To search for potential consequences of these microbial changes, the researchers took stock of microbial genes associated with metabolic pathways. Microbes in people with PD expressed lower levels of genes involved in the degradation of D-glucuronate, a chemical needed for excretion of drugs and toxins in the urine. The patients had higher levels of genes involved in tryptophan metabolism. Tryptophan is a precursor to serotonin; interestingly, people with PD tend to have lower levels of both. However, Wüllner pointed out that it is unclear how much gut bacteria contribute to overall serotonin levels, as human cells also metabolize tryptophan.

The researchers also inferred potential biological consequences based on the known functions of some microbial species. Akkermansia muciniphila—a species PD patients had more of—degrades mucin, an enzyme that breaks down the mucosal lining of the intestine. This bacterium is therefore thought to improve gut barrier function, which is commonly compromised in people with PD. However, the species has also been implicated in inflammation. On the other hand, people with PD had less Prevotella and Eubacteria, both of which produce short chain fatty acids (SCFAs). In particular, Prevotella is more prevalent in the gut of people in non-Western countries with diets rich in fiber, the substrate of SCFAs. While some studies have associated these SCFAs with reduced inflammation, recent studies in mice have implicated them in activating microglia in the brain, and exacerbating α-synuclein pathology 

Despite the mouse data to the contrary, Wüllner hypothesizes that overall, SCFAs have an anti-inflammatory effect in the human gut, and perhaps a therapeutic effect in the brain. The researchers aim to test this by putting some PD patients on a high fiber diet, and thus boosting SCFA production by Prevotella and other species.

Friedland added that the role of these microbially-derived fatty acids neurodegenerative processes deserves further investigation. “This may be a mechanism by which neuroinflammation (which is a component of the Parkinson process in the brain) is influenced by the microbiota,” he wrote.

The researchers employed a statistical algorithm that predicted microbiome alterations were a consequence, not a cause, of PD pathogenesis. However, Wüllner was quick to note that accurately inferring causality will require a much larger sample size.—Jessica Shugart

 

http://www.alzforum.org/news/research-news/rumblings-parkinsons-gut-microbiome-shifts-early-stage-disease

Impulse Control Disorders in Parkinson's Disease: Building Physician, Patient Awareness

April 28, 2017  Linda Peckel 

Clinicians should ask about ICDs at all clinical visits, as they can occur years after initiating treatment.

Impulse control disorders (ICDs) are increasingly becoming an area of focus in the treatment of Parkinson's disease (PD), due to their emergence in many patients as the result of dopaminergic therapies including dopamine agonists (DAs) and less commonly, levodopa.

The most frequent types of ICDs include 4 behaviors: compulsive eating, excessive gambling, compulsive shopping, and compulsive sexual behavior. Other ICD-related behaviors seen less frequently include punding (stereotyped, repetitive, non-goal directed behaviors or excessive hobbyism) and dopamine dysregulation syndrome (DDS) (compulsive PD medication overuse).1,2

Epidemiologic research indicates that the main ICDs are most likely the result of chronic DA use, particularly at higher dosages, while DDS is more likely to be triggered by chronic use of shorter-acting, higher-potency dopaminergic medications including apomorphine and levodopa.1,3,4

Daniel Weintraub, MD, professor of psychiatry at the Perelman School of Medicine at the University of Pennsylvania, Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC) in Philadelphia, and co-investigator in the DOMINION study,5 told Neurology Advisor that the dopamine connection to the expression of ICDs is well established, given the strong association with dopaminergic therapy in the context of PD treatment and imaging studies of the dopamine system. “All short-acting dopamine agonists seem to have the same impact,” Dr Weintraub said, “and there is a suggestion, although not clearly established, that long-acting oral agents or patch formulations may be less likely to cause ICDs compared with short-acting agents.”

Prevalence

The reported occurrence of the primary ICDs associated with PD is extremely broad, with prevalence estimates ranging from 3.5% to 42.8%.6 The DOMINION trial4 found an estimated rate of 17% in patients with PD taking DAs, while a 2016 cross-sectional study by Vela, et al7 reported that DA treatment was associated with a 7-fold increased risk of developing an ICD in patients with early-onset PD.

The ICARUS (Impulse Control disorders And the association of neuRopsychiatric symptoms, cognition and qUality of life in ParkinSon disease) study, reported recently by Antonini, et al6 in the Journal of Neurology, Neurosurgery and Psychiatry, found the prevalence of all 4 ICD types remained stable across the 2-year study period.

ICARUS was a large-scale, prospective, multicenter observational study of the prevalence of individual ICD behaviors in a cohort of 1069 patients with PD who had been pharmacologically treated for a minimum of 6 months.5 The investigators also reported that while the prevalence of ICDs related to the use of DAs and levodopa were similar (26.7%, 64/240 vs 25%, 56/211), the combination of DAs and levodopa was associated with a higher rate of ICDs (30.1%, 179/594).6

Amygdalar Mechanisms

Impulse control disorders are thought to be related to impaired function of decisional impulsivity associated with rapid, disinhibited decision-making, rather than motor impulsivity.2  They may comprise a number of features including delay discounting (an attraction to small, immediate rewards over larger, delayed ones), reflection impulsivity (rapid decision-making), risk taking, reduced sensitivity to adverse outcomes, and response conflict.2

Jennifer Goldman, MD, MS, FAAN, of Rush Medical Center in Chicago, Illinois investigated the roots of neuropsychiatric issues in PD, including cognitive dysfunction and ICDs.7 One proposed mechanism she found was amygdalar dysfunction that could affect behavioral signals to trigger fear, anxiety, and compulsive behaviors.8,9 

Known as the pain-pleasure center, the amygdala generates rapid, unconscious emotional and cognitive responses to sensory input.8,9 One of the primary functions is fear modulation — evaluation of situations for the initiation of the fight-or-flight response. These subliminal fear signals are processed unconsciously using visual pathways that have been shown to overlap with emotional pathways that may heighten arousal to both real and imagined (dissociated) stimuli.8,9

The inhibitory mechanisms in the amygdala involve mostly gamma-aminobutyric acid (GABA) neurons, which are largely regulated by dopamine. “Physiological dopaminergic modulation of the amygdala's response to emotional processing follows an inverted U-shaped curve,” Dr. Goldman wrote.8,9 Affective behaviors including ICDs are then triggered in stressful situations as a result of dopaminergic disinhibition.10,11 In healthy individuals, this response was shown on magnetic resonance imaging (MRI) to be initiated in the amygdala by levodopa.12

Impulse control disorders are among the positive or “plus” symptoms of amygdalar dysfunction, believed to be triggered by D2/D3 dopaminergic overstimulation in predisposed individuals.8 An interesting physiological finding by Biundo, et al13 pointed to a potential cause of a plus dopaminergic response when they discovered significant increases in gray matter (GM) volume on MRI in the left amygdala of patients with PD exhibiting ICDs.13 These patients also demonstrated cortical thinning of the frontostriatal circuitry, along with reduced volume of the corpus collosum and nucleus accumbens.12 The investigators hypothesized that preserved amygdalar function in these individuals might put them at higher risk of ICDs when they are treated with levodopa or dopamine agonist therapies.13

Treatment of ICDs

The main treatment for ICDs is stopping drug therapy or dose reduction, Dr. Weintraub suggested. “Deep brain stimulation (DBS) — which can lead to dose reduction — psychopharmacology (antidepressants, naltrexone), and psychotherapy (cognitive behavioral therapy), may all be beneficial,” he said.

The majority of patients with PD who take DAs or levodopa do not go on to develop ICDs, and the dopaminergic effects may not appear immediately in patients who do, so monitoring is an important part of PD therapeutic management. The potential for ICDs is generally not discussed early in the course of PD, Dr Weintraub explained, but usually comes up later, after treatment is initiated. “A patient really should be notified of the possibility of developing an ICD before initiating any dopaminergic treatment for PD, particularly dopamine agonists,” he said. “And then it should be asked about at all clinical visits, as ICDs can have their onset years after initiating treatment.”

References

1. Weintraub D, David AS, Evans AH, et al. Clinical spectrum of impulse control disorders in Parkinson's disease. Mov Disord. 2015;30:121-127.
2. Voon V, Napier TC, Frank MJ, et al. Impulse control disorders and levodopa-induced dyskinesias in Parkinson's disease: an update. Lancet Neurol. 2017;16:238-250.
3. Zhang G, Zhang Z, Liu L, et al. Impulsive and compulsive behaviors in Parkinson's disease. Front Aging Neurosci. 2014;6:318.
4. Weintraub D, Nirenberg MJ. Impulse control and related disorders in Parkinson's disease. Neurodegener Dis. 2013;11:63-71.
5. Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol. 2010; 67: 589–95.
6. Antonini A, Barone P, Bonuccelli U, et al. ICARUS study: prevalence and clinical features of impulse control disorders in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2017;88:317-324.
7. Vela L, Martinez Castrillo JC, Garcia Ruiz P, et al. The high prevalence of impulse control behaviors in patients with early-onset Parkinson's disease: A cross-sectional multicenter study. J Neurol Sci. 2016;368:150-154.
8. Goldman JG. Neuropsychiatric issues in Parkinson disease. Continuum. 2016;22:1086-1103.
9. Diederich NJ, Goldman JG, Stebbins GT, et al. Failing as doorman and disc jockey at the same time; amygdala dysfunction in parkinson's disease.  Mov Disord. 2016;3:11-22.
10. Janek PH, Tye KM. From circuits to behavior in the amygdala. Nature. 2015:517:284-292.
11. Pape HC, GABAergic neurons; gate masters of the amygdala, mastered by dopamine. Neuron.2005;48:877-879.
12. Delaveau P, Salgado-Pineda P, Micallef-Roll J, et al. Amygdala activation, modulated by levodopa during emotional recognition processing in healthy volunteers: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2007;27:692-697.
13. Biundo R, Weis L, Facchini S, Formento-Dojot P, et al. Patterns of cortical thickness associated with impulse control disorders in Parkinson's disease. Mov Disord. 2015;30:688-695.

http://www.neurologyadvisor.com/movement-disorders/impulse-control-disorders-in-parkinsons/article/653534/

Design students build technology into futuristic furniture

By Jennifer Allford, for the Faculty of Environmental Design
For May 2, 2017

Master of architecture students combine sensors and critical theory in their senior research studio

The Swarm desk is a flexible work space for someone with Parkinson’s disease. Photos by Riley Brandt, University of Calgary

Imagine a work space that can change form with a simple gesture to suit someone with Parkinson’s disease. Or a chair covered in plastic hair and sensors that will fold around an autistic user, shielding them from sensory overload. Or climbing into your own private pod to escape the office and tune in to a projection, some music or nothing at all.

The three startling prototypes were designed and built by master of architecture students in the Faculty of Environmental Design at the University of Calgary in their semester-long senior research studio.“There was an agenda to design for someone who is not yourself,” says Barry Wylant, associate professor in EVDS and industrial designer. His students also had to incorporate emerging technologies and address one of four critical theories — different ideas around changing society.

“It’s been an intense process,” says Wylant. “There was a significant investigation into users, into the critical theories as well as into the emerging technologies that we can use and how they affect the way people interact with the pieces.” 

He was thrilled with the results:

A desk you create with a gesture

SWARM blends Italian Futurism, a critical art theory celebrating the machine, with sensors and artificial intelligence technology to create a flexible work space for someone with Parkinson’s disease, providing privacy when they need it. “It’s essentially a swarm of 8-by-8 by 48-inch-long bricks that are controlled through gesture sensors,” says Eric Free, who built Swarm with Jubril Idowu, Alex Raymundo, and Xumin Wang. “You can summon the blocks with a gesture and move them to make space, whether a desk or a meeting space or a chair. It’s a very technologically expressive work station that can accommodate all kinds of different ways that work happens.”

Seating that cocoons you (above)

Mobi, a flexible white surface that also builds off the ideas of Italian Futurism, was conceived for someone on the Autistic Disorder Spectrum who may have sensory issues and social anxiety. Sensors are embedded in the structure’s hair. “In order to change the position or make a seat, you swipe the hairs and it will read your response,” says Brady Horner, who made Mobi with Jayde King, Madeleine Chu and Anne Gorsalitz. Although it was designed form people with sensory issues, Mobi may also appeal to those in open office environments. “Open offices can be unpleasant because it’s loud and people are constantly bugging you,” says Horner. “Mobi has the ability to adapt to the situation to close you off and cocoon you.”  

Climb into the POD to escape (above)

The POD, for Perruque on Demand, is a private space placed sporadically through Plus 15s for office workers to climb in and “take back moments of the work day” for their own personal gain. That idea of reclaiming the workday — “perruque,” the French word for wig — is expressed in French intellectual Michel de Certeau’s critical theory.

“Inside there are LEDs and a projection system so you’re getting that experience of sound and light that encompasses the entire interior of the POD, immersing yourself in the experience of your smartphone,” says Charlea Greig who created the POD with Cass Milford, Stephanie Karpuk and Noah Jarvis.  “You have flexibility in choosing what you want to do or relax or re-centre yourself away from the everyday office environment.”

As well as building the prototypes, students developed a “persona” to use the piece, a short film, mood boards and design brief. “In a big chunk of our world, our relationship to technology and the compromises we make to use it become brushed under the carpet,” says Wylant. “If we are making a hunk of technology what’s the real relationship with people who are using it, good or bad. And with most pieces of technology, it’s both.”

This Senior Research Studio is possible though support of Teknion and McCrum’s Office Furnishings.

http://ucalgary.ca/utoday/issue/2017-05-02/design-students-build-technology-futuristic-furniture

Parkinson’s disease treatment : QBRI expertise to help clinical trials

April 28, 2017

Dr Omar M Ali El-Agnaf in his lab

A research team headed by Dr Omar El-Agnaf, acting executive director of Qatar Biomedical Research Institute (QBRI), one of Hamad Bin Khalifa University’s (HBKU) three national research institutes, has been selected by the Austrian biotechnology company, AFFiRiS AG, to evaluate selected parametres in clinical trials on an innovative anti-alpha-synuclein immunotherapy-based approach to treating Parkinson’s disease.

Research carried out by Dr El-Agnaf’s team of scientists that uses novel techniques to identify biomarkers of Parkinson’s disease in human blood and cerebral spinal fluid samples attracted the attention of AFFiRiS AG, a leading name in the field of developing immunotherapies that target chronic diseases with unmet medical needs.

AFFiRiS AG called upon the Qatar-based team to use the tools and expertise developed at HBKU to validate the target engagement of alpha-synuclein for the company’s first-of-its-kind Parkinson’s disease immunotherapy approach. The product has been developed in Europe by a team of scientists and its pre-clinical and clinical development has been supported by Michael J Fox Foundation.

Using the team’s novel analysis techniques, the researchers at HBKU will assess the product’s ability to engage with the target, alpha-synuclein. QBRI’s scientists will explore novel biomarkers discovered by them that facilitate early diagnosis and treatment of Parkinson’s disease and use the technique they have developed at HBKU to assess the magnitude of target engagement of this new immunotherapy-based compound.

Dr. El Agnaf’s group, based within QBRI’s labs within Education City in Doha, specialises in biomedical research that focuses on Parkinson’s disease and related neurodegenerative disorders, are also involved in the development of drugs that target the treatment of neurodegenerative diseases.

QBRI has established itself as a leading disease-focused research institute in the Middle East. Currently, QBRI operates three research centres that target different diseases: the Neurological Disorders Research Centre, the Cancer Research Centre, and the Diabetes Research Centre.

http://www.gulf-times.com/story/546094/Parkinson-s-disease-treatment-QBRI-expertise-to-he

Wise Buy? Focused Ultrasound Therapies

April 28, 2017  by Paul Raeburn  Contributing Writer, MedPage Today

Exciting technology, but now sold to patients on slim supporting evidence

Do a search on focused ultrasound (FUS), and you'll quickly discover that it's a kind of fairy-tale cure, helpful in the treatment of almost everything: Parkinson's disease, uterine fibroids, atrial fibrillation, congestive heart failure, Alzheimer's disease, depression, diabetes, obesity, cancers of the prostate, kidneys, pancreas, bladder, breast, and dozens more.

FUS also has its own website, run by the Focused Ultrasound Foundation, a manufacturer-supported organization dedicated to "accelerating the development and adoption of focused ultrasound." Neal Kassell, MD, the founder and chairman of the foundation and a professor emeritus of neurosurgery at the University of Virginia School of Medicine, said in a 2015 TEDx talk that FUS "could improve the health and happiness of millions of people around the world."

The technology has not, however, been greeted with universal acclaim. It has proven controversial enough in the treatment of essential tremor -- for which it has FDA approval -- that the American Academy of Neurology's 2017 meeting this week featured it in a plenary-session "controversies in neurology" debate.

At that session, Paul Fishman, a neurologist at the University of Maryland, took the "pro" side, arguing that serious adverse event rates with FUS are dramatically lower than with a more established alternative -- deep brain stimulation (DBS). Fishman also said that DBS has a significant incidence of hardware failure requiring additional surgery.

Michael S. Okun, MD, the chairman of neurology at the University of Florida -- who argued the "con" side -- did not dispute those points, but noted that the opportunity for later surgery was an advantage, because mistakes and complications can often be corrected. That's not possible with FUS, which burns away tissue. "You can't troubleshoot a focused ultrasound problem," he said.

Okun also noted that the target for FUS in Parkinson's disease is very small -- "the size of a squashed pea" -- and can't be visualized well in MRI scans. That, along with difficulties focusing the beam because of interference from the skull, means off-target ablation is likely to occur periodically. And FUS can be used on only one side of the brain, because thalamic ablation on both sides has consistently been shown to have unacceptable adverse effects. DBS, in contrast, can be safely used on both sides to achieve more complete symptom control.

Okun did acknowledge that FUS holds a great deal of promise for other neurological applications, calling the potential of using it to open the blood-brain barrier to allow larger molecules into the brain, "brilliant."

In an interview the day before the debate, Okun said that using FUS to treat essential tremor "is like trying to make an omelet without opening the egg ... You're shooting from outside the brain." And the targets are not only small but also "somatotropically organized." Particular regions of the brain are mapped to specific parts of the body, and a misplaced lesion can have harmful side effects. A wrongly mapped attempt to ease a tremor in an arm, for example, could weaken a leg, leaving a patient unable to walk, Okun said.

Further, he said, neurologists already have a powerful means of treating essential tremor. "The gold standard of making lesions in the brain is radiofrequency [ablation]. Once you've mapped a brain out and you know where the structures are, you can insert a probe and burn it."

Fishman said before the debate that the use of FUS for Parkinson's disease could be a cheaper alternative to deep-brain stimulation. And he said he is eager to see it approved by the FDA, because until then it isn't covered by insurance. "We have a waiting list of over 200 patients," he said, but he can do the procedure only on those who can pay $25,000-$35,000 out of pocket. Asked if he was excited about FUS, he said, "It's a gas!"

At the conclusion of the AAN debate, audience members were asked whether they sided with Okun or Fishman. Okun's arguments "con" won with 90% of those voting, but most audience members didn't raise their hands for either one, suggesting that they found both sides persuasive.

Kassell acknowledged the criticism, but it doesn't dampen his enthusiasm. He was able to persuade a Charlottesville, Va., neighbor, John Grisham, the best-selling author of legal thrillers, to write a short book called The Tumor, which shows how FUS could one day be used to treat glioblastoma. "This is not fiction," Grisham said. "This is the future, and it is rapidly approaching."

FUS operates by a variety of mechanisms, including ablating tissue, delivering drugs in high concentrations to a particular point in the body, and enhancing the effectiveness of cancer immunotherapy drugs -- 18 different mechanisms in all.

Kassell said there are several areas in which the technology is nearest to routine use. One is to deliver drugs to a precise target. The drugs can be tucked inside hollow lipid spheres which are injected into the bloodstream. "You can inject millions of these into the bloodstream, and they are everywhere blood goes. But the drug is inactive except where the ultrasound is focused. At that point the microbubble bursts and delivers its pharmacological payload," Kassell said.

A second is to ablate tissue, and a third is to modulate the immune system, meaning ultrasound might have a role to play in enhancing the effectiveness of cancer chemotherapy or other drugs.

Kassell said FUS has been approved by the FDA for three things in addition to essential tremor: uterine fibroids; pain from bone metastases; and the ablation of prostate tissue to treat prostate cancer or BPH. But more are coming.

"As of today, there are almost 80 clinical indications in various stages of research and development," Kassell said. He notes that FUS can potentially be much cheaper than alternative treatments. Deep-brain stimulation for Parkinson's disease costs some $60,000 to $100,000, he said, but ultrasound can do the job for one-third of that. (Okun said in the interview that data does not yet exist to show that FUS is cheaper.)

Kassell said that the foundation works with three dozen companies that make ultrasound equipment, but that the foundation is not intended to promote commercial interests -- only to spread interest in what he sees as an extremely valuable new technology. "What we're doing here at the foundation is to be engaged in a variety of activities which can move quickly to save people and save lives," he said.

Prostate cancer is one of the applications for which ultrasound looks most promising. Last year, at the annual meeting of the American Urological Association, researchers reported that almost 90% of patients with early prostate cancer remained free of radical intervention two years after treatment of a single lobe with high-intensity FUS. The report generated "cautious optimism" that the technology could play a role in the treatment of early prostate cancer.

Another application is for use with Alzheimer's disease. FUS's ability to gently open the blood-brain barrier can allow amyloid-scavenging drugs to reach and potentially destroy plaques characteristic of Alzheimer's disease.

The first human trials for Alzheimer's disease were launched in March by a neurosurgeon, Nir Lipsman, MD, PhD, at Sunnybrook Health Sciences Center in Toronto. Two of a total of six patients were treated to assess the safety of the technique before it's used more widely.

Other Alzheimer's specialists were divided over whether or not human trials are premature, but because ultrasound has been used in the brains of Parkinson's patients, some felt that it was likely to be safe for use in Alzheimer's disease. The study is also predicated on the fact that the plaques are a cause of the illness; not everyone agrees that that's the case.

Now we come to the question: Is FUS a wise buy?

"I would say definitely yes," said Fishman. "There is a product out there already, which is deep brain stimulation. For a certain fraction of those patients, they would likely opt for FUS, which is a cheaper technology, and less onerous." Asked if neurologists are excited by FUS, Fishman said, "The field is still very unaware of this technology. There may be a thousand articles in the medical literature on DBS and maybe 50 on this." He also offered "a little disclaimer ... I have the passion of a recent convert."

Asked the same question, Kassell said, "The answer is ... it depends." The economics will be hard to sort out until insurance companies begin to cover it, he said. "Some sites can fight with the insurance companies, but there is not a lot of reimbursement. People are paying cash."

At the same time, he's frustrated and unhappy at the pace of research. Asked if he was enjoying this work during what could be a relaxing retirement, he said no. Too often, he said, he sees people who could be helped, and he knows that the data is not yet there to offer them the treatment.

Kassell's vigorous promotion of FUS could backfire -- it invites skepticism. Far too many treatments that work like magic in mice or a handful of patients fail in proper clinical trials.

It's too soon to know whether FUS is one of them. It's not yet a wise buy. But when the evidence comes in, it might be. It's simply too early to dismiss it or embrace it.

Wise Buy, a MedPage Today series, assesses therapies -- new and old -- to determine if the treatment is not only a wise choice, but also a wise buy.

https://www.medpagetoday.com/radiology/therapeuticradiology/64885

SaveSave