I've just been diagnosed with Parkinson's disease

September 09, 2016 

Mike Oliver (Ginnard Archibald, GArchibald@al.com)

I've just been diagnosed with Parkinson's disease.

When I said those words to a small gathering at a Parkinson's support group, there was a catch in my voice, my lip trembled. When I said those words a few days later to my two immediate supervisors at work, there was a catch in my voice and my eyes teared upIt was fresh pain. Raw.

Weeks have gone by since the Aug. 11 diagnosis of Parkinson's. I'm still trying to wrap my 56-year-old brain around it. I've got time. It's a slow moving disease. There is no cure.

Physically it only gets worse. Will I lose my ability to walk? At some point, maybe, yes. Will I lose my memory?  At some point, maybe, yes. Dementia sometimes can go hand-in-hand with Parkinson's, hopefully later than sooner.

In a nutshell, here's what's happening in one part of my brain: Neurons are dying. These neurons are counted on for producing a chemical called dopamine. This diminished dopamine results in less control over the body's movements and emotions. Think Michael J. Fox's swooping arm movements or Muhammad Ali's steady shaking when lighting the Olympic cauldron in Atlanta in 1996.

No one knows the cause of these neuron deaths or how to keep it from progressing. But medication and exercise have proven to slow the progression of symptoms.

In retrospect, I now know I had Parkinson's disease long before my official diagnosis. I had sleep problems for more than a year – a common Parkinson's symptom. I had increasing anxiety that felt very physical for many months, also a Parkinson's symptom.

In a nutshell, here's what's happening in one part of my brain: Neurons are dying.

As a long-time health care reporter, I'd often imagine myself with symptoms of whatever rare deadly disease I was writing about at any given time, before logic would snap me back to reality. But this time was different; I couldn't shake the feeling something was wrong.

I had relatives and close friends asking me if I felt all right. They noticed I was hunching my shoulders at times, walking and talking slower.

At least six months in advance of my diagnosis, while playing my favorite sport, pick-up basketball, I noticed my right arm sliding up unconsciously against my side with my finger pointed. Then I read a story on AL.com about a person with Parkinson's who talked about how one of his symptoms was the 'classic gunslinger' position of his hand and arm: arm perched at hip or side, looking as if ready to draw an invisible gun from an invisible holster.

That was me. I knew then I had it.

But knowing it and accepting it are two different things.

I sought to have it diagnosed by a neurologist. My wife, Catherine, and my 24-year-old daughter, Claire, came along on that Aug. 11 appointment.

At UAB's Division of Neurology and Movement Disorders at Kirklin Clinic, Dr. Marissa Dean had me go through a battery of tests, checking motor skills like walking, balance, coordination. With Parkinson's there is no standard diagnostic test such as a blood test or a brain scan. Rather doctors take a history and observe a series of movements and coordination exercises.

One test involved putting the palm of my hand on my leg and then turning it over -- palm, back of the hand -- over and over to see how quickly I could turn my hand.

It reminded me of hambone, a percussive body performance of which I have some skills.

In the middle of the testing I said "Watch this."  I began slapping my thigh with an upward motion following through with a slap on the chest. Repeat, faster and faster, hambone!

 The doctor seemed dazzled; my wife bemused; my daughter started laughing.

"Now can someone with Parkinson's do that?" I asked. Apparently so. 

Moments later, Dr. Harrison Walker went through some more tests and confirmed Dean's observations:

I'm sorry to tell you, you have Parkinson's disease.

The postscript to this is I don't know what the future holds.

They say Parkinson's disease is unique to the individual, ranging from mild to severe. My symptoms are minimal now. I'm doing the things we know work to keep symptoms at bay: exercising, avoiding excessive stress, eating healthy, taking the prescribed medication, seeking support.

I'm still working my job as Senior Managing Producer at AL.com; I'm still playing pick-up basketball; and, on occasion, when the mood strikes, I'm doing a little hambone.

=======================================

Mike Oliver is a veteran journalist as editor and reporter in investigative work, health care and politics. He started at the Birmingham News in 1982 out of Auburn University and went on in 1987 to work for 12 years at the Orlando Sentinel, followed by 10 years at California's Bay Area News Group (Oakland Tribune, Contra Costa Times). He came full circle in 2011, returning to AL.com/The Birmingham News. He is married to Catherine, a Presbyterian pastor, and has three grown daughters.

For more information and to help find a cure go to: Michael J. Fox Foundation; Parkinson's Disease Foundation; and Davis Phinney Foundation. For information on support groups in Alabama go to Parkinson's Association of Alabama.

http://health.einnews.com/article/343960099/pBkanTCUcpZ5vNan

How dad talked through Parkinson's

September 9, 2016

SINGAPORE - A new centre at a Bishan Street 13 void deck now offers physiotherapy, art therapy and other services for people with Parkinson's disease. After Alzheimer's disease, this is the second most common neuro-degenerative disease here. About 4,000 people are affected, most of whom are aged over 50, but more in Singapore are now being diagnosed in their 40s.

Doctors usually tell patients and their caregivers that Parkinson's disease is a brain condition that affects the motor functions, causing tremors, immobility, stiffness and poor balance. They like to reassure them that it is not a psychiatric illness.

While all that is quite true, the physical deficits the disease causes lead to a host of neuro-psychological problems.

Most patients experience a cycle in which it is not just their physical agility but also mental energy that fluctuates from "on" to "off", and vice versa, usually because of the timing of their medications. From living independently to becoming progressively more dependent on caregivers, the Parkinson's patient usually goes through stages of denial, panic, anger, helplessness and depression.

Living with a chronic degenerative disease of any sort is hard to come to terms with but many doctors and family members may not quite grasp the patient's first-hand experience of the condition. As such, they may not quite comprehend his experiential challenges.

My father who died seven years ago suffered from Parkinson's. During the years of his deterioration, I often coaxed him into talking about his experience of the illness.

Over the last few weekends, I have finally been able to retrieve the videotapes I made of our conversations and watch them in an attempt to recover a sense of his first-person experience of the adversities he faced.

Dad described to me his cyclical periods of near immobility and mental lethargy that alternated with periods of excessive movement and mental energy.

The periods were quite sharply separated from one another, he said, as if someone turned a switch on or off inside his head at the appropriate time.

In the periods of a day before the medication levodopa restored both movement and clear thinking, his mind would feel "clouded", he said. This upset him no end, for not only could he not move about freely but he also could not communicate lucidly.

The cyclical energetic periods were experienced as a kind of relief from the sharply delineated periods of ennervation and ennui.

But the relief that came with each dose of levodopa was never a completely satisfying one, because it came with a frenetic level of activity that felt out of control.

The mobility that came with those periods felt frenzied and artificial, dad said, so his body no longer felt like it was completely his own. He felt that his old - and real - self was "still inside", imprisoned by a new self that irritatingly made its presence known to all and sundry through this disharmonious "outer" body.

Apart from the mobility and balance problems caused by Parkinson's, dad also had tics called dyskinesias caused by the levodopa itself.

These involuntary abnormal movements of various forms - the word is made up of the Greek "dys" for difficult and "kinesis" for movement - were never completely resolved by treatment. His dyskinesias were mainly writhing movements of the head and neck, along with his arm being pulled behind the back.

The sustained muscle contractions in these dyskinesias gave dad quite a lot of pain. But most of all, the muscle contractions made him quite angry because the grotesquerie they caused made him physically unable to project the persona of that autonomous, articulate and capable man which he used to be.

He would try to conceal the dyskinesias and mobility loss. But as his condition deteriorated, the attempts to do so only made things worse. Dad said if he tried to hide his hands by making a fist, so the fingers would stop moving around, say, his contortions would become more pronounced.

Nevertheless, he tried to organise his life around the four times he took his levodopa every day. He could not just get up at eight o'clock, say, and head straight out of the house to join his retiree friends for taiji. Instead, he had to sit in his armchair and wait for the pills to take effect before he could move.

The brain wasn't unreflectively or spontaneously telling the body to do things as before, dad said. He had to consciously tell himself to put one foot in front of the other, step by step. Sometimes, while walking, he would freeze and stumble.

Mind and body were no longer united, he said, and routines or activities had to be planned around his symptoms and medication, which sucked the oxygen out of his joie de vivre.

Also, the levodopa sometimes didn't quite work, so dad felt that the pills were in control of his life. If the pills did not work, he would just have to sit there, waiting fecklessly for the next dose hours later as he could not overdose on it.

Eventually, he just stopped meeting his buddies. But to the very end, dad was always talking - whenever he could - about who he really was and the unreal disconnect between body and self. For him, these concerns were as important as the immobility, tremors and dyskinesias.

This was dad's lived experience of Parkinson's, something the physician and family caregiver might want to spend time on with their own patient. Talking about it could help a patient achieve a modicum of control over his predicament.

I hope it did for dad.

andyho@sph.com.sg

http://health.einnews.com/article/343927249/10pIqFfwq2xDZp8C

Patient looks to new ultrasound treatment to relieve tremors

September 9, 2016 by Molly Schulman 

Alexandra Lebenthal has kept the condition that makes her hands uncontrollably shake a secret throughout her life. Living with essential tremor since she was 3, Lebenthal has struggled to pour drinks, eat food, shake hands and swipe her subway MetroCard. Despite her success as president and CEO of a boutique investment bank, the tremors have made her feel self-conscious at professional and social events.

Since undergoing MRI-guided ultrasound ablation, a new non-invasive treatment for tremors being offered at Weill Cornell Medicine, on Aug. 22, Lebenthal is enjoying new confidence in her dominant left hand. The technique relies on MRI technology to pinpoint the exact location in the brain where the tremors originate, then administers high-intensity focused ultrasound to destroy problematic tissue. The U.S. Food and Drug Administration recently approved the procedure, also known by its acronym HIFU – which has successfully treated breast and prostate cancer – for use on essential tremors in the brain.

"At my company, we invest money for people, so if I am shaking, people may have the concern that I am not trustworthy or that I am nervous," Lebenthal said.

Two days after the procedure, part of a clinical trial of the device, Lebenthal was holding her coffee mug and pouring beverages with one hand instead of two, and getting used to the sensation of holding a pen loosely, rather than tightly gripping it, while she signed her name. "It's amazing because my hand has no tremor anymore," said Lebenthal, 52. "I keep looking at it, like 'Oh my God, is it going to come back?'"

Essential tremor is the most common of all movement disorders. Unlike Parkinson's disease, it does not have any other accompanying symptoms and is not life-threatening.

Her tremors, which have mostly existed in her hands, have worsened as she's aged. Because such tremors are often treated with medication that does not target the tremors directly, their effects on patients' shaking can be limited. Lebenthal has tried various medications to treat her tremors, but none of them has worked long-term.

During her HIFU treatment, Lebenthal wore a fitted helmet that holds 1,000 transducers or beams of ultrasound waves. While individually the waves don't have enough energy to damage brain tissue, when they are combined and directed at the same target from different directions, they "create a high amount of energy that can destroy a small area of the brain," said Dr. Michael Kaplitt, vice-chairman for research in the Department of Neurological Surgery at Weill Cornell Medicine, who performed Lebenthal's procedure, during which she remained awake

                       

Kaplitt became the first physician in New York to use HIFU treatment in the brain as part of the clinical trial in July, when he watched a trial participant's tremors disappear in a matter of minutes. "This new technology provides a 21st century solution to a problem that's been around for a long time and continues the trend in neurosurgery toward offering less invasive therapies for a variety of brain disorders," said Kaplitt, an associate professor of neuroscience and neurological surgery in neurology and otolaryngology at Weill Cornell Medicine and a neurosurgeon at NewYork-Presbyterian/Weill Cornell Medical Center.

The main option for essential tremor patients who do not respond well to medical therapy is deep brain stimulation (DBS), which involves placement of an electrode into the same area of the brain targeted by HIFU and implantation of a battery under the skin in the chest to power the therapeutic electrical impulses. DBS, which has been offered by Kaplitt and his team at Weill Cornell Medicine for movement disorders for more than 15 years, remains a viable option for patients who may not be candidates for HIFU therapy.

Trial participants from across the U.S. who've undergone the HIFU treatment in other parts of the country have seen significant improvements in tremor, with some having return of function to normal, according to the FDA and a study published Aug. 25 in the New England Journal of Medicine. In that study, about a third of subjects experienced a loss of control of body movements following the procedure (ataxia) as well as numbness following the procedure – adverse events that persisted at 12 months for 9 percent and 14 percent of patients, respectively. Weakness occurred in a small percentage of subjects, persisting rarely. One subject had persistent finger pain a year after the procedure.

Lebenthal found out about HIFU after stumbling upon a video about it on Facebook. "When I saw the video, I thought, 'This is amazing!'" Lebenthal said, adding that she reached out to Dr. Frank Petito, the Finbar and Marianne Kenny Professor of Neurology and a professor of clinical neurology at Weill Cornell Medicine, and a neurologist at NewYork-Presbyterian/Weill Cornell, who informed her that the institution was installing the device used to perform the procedure. It turned out Dr. Philip Stieg, chairman of the Department of Neurological Surgery at Weill Cornell Medicine and neurosurgeon-in-chief at NewYork-Presbyterian/Weill Cornell, had a longstanding interest in HIFU technology and was spearheading acquisition of the device in collaboration with Dr. Robert Min, chairman of the Department of Radiology and radiologist-in-chief at NewYork-Presbyterian/Weill Cornell.

Lebenthal jumped at the opportunity to enroll in the Weill Cornell Medicine clinical trial.

"I have been so overwhelmed by how excited people involved at Weill Cornell Medicine and NewYork-Presbyterian seem to be," Lebenthal said. "There's this whole supportive group here … I really felt I was part of something special."

The procedure took three hours to complete. Periodically, physicians would ask her to draw a straight line or a spiral to gauge how well the therapy was working; ultimately, her tremors receded by 100 percent, Kaplitt said.

Eventually, he said, scientists could study the technique's application to a variety of neurological disorders ranging from Alzheimer's disease to addiction. His laboratory has also been investigating ways to use HIFU to non-invasively deliver gene therapies to specific brain regions. Kaplitt has previously researched delivery of the same gene therapies in human patients with invasive injections.

"We now have this opportunity to provide safe, non-invasive therapy to try and treat those types of diseases. This represents not only a new opportunity for essential tremor patients but also provides a platform of development for even more cutting-edge non-invasive technology," Dr. Kaplitt said.

While Lebenthal is marveling over the sophistication of the technique, she is also delighting in the simple things she is suddenly able to do.

"I've had to grip a pen so tightly to write without shaking and it's been something that actually hurt," she said. "When I had to sign a document before leaving the hospital, it was the strangest feeling, like holding a feather. I'm looking forward to doing that more."

More information: W. Jeffrey Elias et al. A Pilot Study of Focused Ultrasound Thalamotomy for Essential Tremor, New England Journal of Medicine (2013). DOI: 10.1056/NEJMoa1300962 

Journal reference: New England Journal of Medicine
Provided by: Cornell University 

http://medicalxpress.com/news/2016-09-patient-ultrasound-treatment-relieve-tremors.html

A blossoming spirit

September 8, 2016

KATE GRIGG/SPECIAL TO THE PACKET & TIMES Miriam Goldberger is developing a therapeutic dance program for those with chronic pain or Parkinson's disease. Gentle Moves dance classes begin Sept. 20 at St. James' Anglican Church in Orillia.

She can't explain why she loves it. Dance is so much a part of Miriam Goldberger, has been since age four. It would be like trying to put into words how it feels to have an arm or a leg. Easier to explain their absence. And dance has never been absent from Miriam's life. Even when she found herself too sedentary while writing a book (Taming Wildflowers), it was Miriam's physical self that stopped dancing, grew arthritic and sluggish, never her spirit.

Miriam's spirit is naturally strong. Enhanced in childhood by the people around her, especially the women. Her mother, a speech pathologist, who went back to school in the 1950s to get her master's degree. Miriam's grandmother, politically active, an accountant at a time when women stayed home or worked at acceptable jobs, nursing or teaching.

Miriam's love for her grandmother extended to the elderly in general. She felt an affinity with them, ran dance classes, dreamed of creating an arts centre for older people. Perhaps it's their spirit that attracts her, the spirit that has carried them through the years and matured into something fine and enduring, particularly poignant as it nears its end, at least its time in a human vessel.

Miriam used to make up stories to tell in dance. Headed into the city on Saturdays (New York City; Miriam was raised in New Jersey) to take in the theatre, the ballet, the symphony, where other stories were told. It was more than her own spirit Miriam wanted to express. It was something bigger, something more inclusive she pursued.

Why else would she leave her job as a sound-effects editor in Los Angeles (Miriam's first husband worked in the film industry), a job Miriam found too technical, too male-dominated, physically confining? Why else, when Universal sent her husband to Toronto (1980), did Miriam return to the things she prized, the spirit of women, the spirit of dance, the spirit of life?

All of it somehow weaving together: her degree in dance and dance history, her interest in childbirth and midwifery, her involvement with fitness and dance classes for women in the midst of bearing children. All of it growing, one thing feeding another, Miriam's spirit enlivening everything she touched, and everything she touched enriching her spirit.

Until Miriam and her second husband, Paul, moved out of the city to live where things grew literally, to Schomberg (1986), taking on a derelict farmhouse (previously inhabited by a motorcycle gang). "What the heck," Miriam thought, knowing a house could be cared for and nurtured, that it could grow into a home. As her interest in growing vegetables and flowers grew into Canada's first pick-your-own flowers farm. And that in turn grew into the Wildflower Farm located outside Orillia (and now exclusively online).

Because people want something alive around them, even when their thumbs aren't green, when they have no time to garden. They need the spark of life that so fascinates Miriam each time it springs from a tiny seed. The same spark that is inside every person but sometimes gets buried or grows weary, in need of replenishment.

As Miriam's spirit needed restoring after she lost her parents, when, six years ago, her mother died. She felt the need to mourn, to go back to where everything began, back to her roots, back to dance, back to school in Boston to get a master's degree in dance therapy. She had to go back in order to start out again, to make something grow again.

And what Miriam is growing are therapeutic dance programs, including Dance for Parkinson's (Miriam trained through the National Ballet School of Canada). Because music and movement have a way of getting past neurological logjams, have a way of lifting depression, of keeping things fluid, of freeing people, building strength and confidence. Because dance can reduce the need for medication and painkillers, can bring people together, let them forget their troubles and reconnect to their earliest selves, when movement, not words, was the primary language.

It's the kind of therapeutic program Miriam would like to bring to all kinds of people. People with dementia and people with cancer, people in long-term care, people with disabilities. "The sky's the limit," Miriam says. That's how far her spirit soars.

So, anyone with Parkinson's, anyone with chronic pain is invited to attend Miriam's What Dance Can Do 10-week pilot program beginning Sept. 20 at St. James' Anglican Church in Orillia. Anyone, male or female, of any age (caregivers, too), can come to the Gentle Moves class, and feel the warmth of Miriam's welcome, feel the spirit that moves her, and follow her into the dance.

Miriam will be on hand at Saturday's Parkinson SuperWalk to share information about the Gentle Moves pilot program. The SuperWalk begins at Emmanuel Baptist Church, 300 Coldwater Rd. W., with a 10:30 a.m. check-in, followed by the walk at 11:30 a.m. Information about the Gentle Moves dance program is also available by emailing miriam@wildflowerfarm.com or whatdancecando@gmail.com.

http://www.orilliapacket.com/2016/09/08/a-blossoming-spirit

Keep moving in the face of Parkinson’s disease

September 8, 2016

Just try to keep Scott Rider from his mission. The 56-year-old has Parkinson’s disease but he will tell you the disease does not have him.

“I’m not going to let it rule my life,” he said. “I’m going to try to rule it.”

Rider was diagnosed nearly 10 years ago but says he knew something was wrong even earlier when he felt himself slowing down during a family vacation.

“My daughter, who was three at the time, kept telling me how slowly I was moving,” he said.

Parkinson's disease is a progressive disorder of the nervous system that affects movement. The disease develops gradually.

National Parkinson Foundation Ohio - Moving Day Columbus

Many people know it for starting with a barely noticeable tremor.

Dr. Andrea Malone, a neurologist at OhioHealth says she and her team take note of not only a tremor, but also slowness and stiffness.

“When we give someone the diagnosis, I like to tell them there’s a lot of hope,” she said. “There’s a lot of things we didn’t know about the disease 50 years ago as neurologists. There’s medications, to exercise, to physical therapy to occupational therapy to other treatments.” 

Risk factors include age—typically patients are between the ages of 40-and 70 years old—genetics and environment. 

The irony of having a disease that affects movement is not lost on Rider. He’s a lifelong runner with awards and records still on the books.

Rider says that training is helping him live with Parkinson’s.

“To perform at a high level at any sport you have to have a lot of drive so I’ve tried to treat Parkinson’s the same way,” he said.

Rider was a 1982 NCAA Track and Field All-American in the 800 Meter, participated in the 1984 Olympic trials in Los Angeles and remains the record holder in the men's outdoor 800 meter at The Ohio State University. 

"It's humbling to know my name's on the same board with Jesse Owens and Butch Reynolds and great people like that,” he said. “Running formed my life had I not had running I wouldn't be the person I am today. “

Scott keeps a blog about his journey with Parkinson’s.

Too see Video:

http://www.10tv.com/article/keep-moving-face-parkinsons-disease

http://www.10tv.com/article/keep-moving-face-parkinsons-disease

Minot Parkinson's support group facilitator awarded Silversteen Community Service Award

September 8, 2016

MINOT, N.D. - The St. Joseph's Community Health Foundation nominated a local Parkinson's support group facilitator for the Silversteen Community Service Award.

Eilene Emily started the support group in 2006 for her husband and friends with the disease but no local support group. Since then the group has grown.

She was awarded for her services in Minneapolis this past June. 

"When you love someone so much it doesn't make a difference when you're up in front, you're just with a family. And so even here today I feel like I'm with my family," says Emily.

"We really hope that they realize and understand that there are others with Parkinson's disease and that there is a community and a family that they can call when there is a need, if they have a question. Eilene has provided that for us, that's why I nominated Eilene for the Silversteen Award because she has bought this and enriched our community with all of the Parkinson's resources and without her I'm not sure we'd have it today," says Shelly Weppler, St. Joseph's Community Health Foundation President.

Emily continues to facilitate the support group every first Wednesday at 1:30 p.m. at Brentmoor Assisted Living.

To see video:

http://www.kfyrtv.com/content/news/Minot-Parkinsons-support-group-facilitator-awarded-Silversteen-Community-Service-Award-392802691.html

http://www.kfyrtv.com/content/news/Minot-Parkinsons-support-group-facilitator-awarded-Silversteen-Community-Service-Award-392802691.html

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GBA Variants Predict Rapid Progression of Parkinson's Disease

September 8, 2016

The pathogenesis of GBA on PD is unclear, although several studies have pointed to disruptions of different molecular pathways that contribute to disease onset.

Of the many known phenotypic variations of Parkinson's disease (PD), mutations of the glucocerebrosidase (GBA) gene are highly associated with more rapid motor disease progression, according to results of a multicenter study reported in JAMA Neurology.

Progression to mild cognitive impairment (MCI) or to dementia was also higher among GBA carriers compared to noncarriers, although this association was predominantly seen in those with polymorphism changes to E326K. Neither GBAmutations nor E326K polymorphisms were associated with increases in tremor scores.

Based on results from 3 previous studies,1-3 in which GBA mutations (associated with the lysosomal storage disorder, Gaucher disease) corresponded to rapid disease progression in PD patients, investigators from 7 sites conducted longitudinal assessments of 733 patients diagnosed with clinical PD according to criteria from the UK Parkinson's Disease Society Brain Bank. The patients were genotyped for all possible mutations associated with Gaucher disease as well as the nonsynonymous polymorphism E326K.

Eleven mutations to GBA were found in the study population, plus 5 variants of unknown significance and 3 types of nonsynonymous single-nucleotide polymorphisms. The investigators were able to adjust for differences in levodopa doses among the cohort. 

The pathogenesis of GBA on PD is largely unclear, although several types of studies have pointed to disruptions of several different molecular pathways that contribute to the onset of the disease. Blood assays previously demonstrated that normal GBA activity appears to be significantly reduced in carriers of polymorphisms as well as GBA mutations compared to noncarriers⁴ and other nonclinical studies (using cell cultures and animals) have pointed to mechanisms of misfolded proteins resulting in accumulations of alpha-synuclean, now widely associated with PD.^5-8

The current study used a special version of the Unified Parkinson's Disease Rating Scale (UPDRS) Part –III assessment standards sponsored by the Movement Disorders Society, to provide a more sensitive measure of disease progression (and particularly of motor signs) than previous studies that relied on Hoehn and Yahr disease staging. By focusing on the presence of GBA mutations in the cohort of patients with probable PD, the investigators were also able to show that the weight of this single genetic factor is at least as great as all other contributing mutations to both cognitive and motor function decline in PD.

The implications of this study clearly indicate that GBA mutations and E326K polymorphism are both predictive of a more rapid progression of motor signs in PD, and that E326K alone is predictive of cognitive decline and further, that these genetic markers are indicative of a more severe clinical course of disease. 

The authors contend that based on their results, GBA genotyping can provide a strong biomarker for disease progression in future therapeutic trials, in both patient selection and in stratification of therapy groups.

References

1. Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993;328(3):176-183.
2. Poewe W. The need for neuroprotective therapies in Parkinson's disease: a clinical perspective. Neurology. 2006;66(10)(suppl 4):S2-S9.
3. Goetz CG, Stebbins GT, Blasucci LM. Differential progression of motor impairment in levodopa-treated Parkinson's disease. Mov Disord. 2000;15(3):479-484.
4. Alcalay RN, Levy OA,Waters CC, et al. Glucocerebrosidase activity in Parkinson's disease with and without GBA mutations. Brain. 2015;138:2648-2658.
5. Keatinge M, Bui H, Menke A, et al. Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein–independent neuronal cell death. Hum Mol Genet.2015;24:6640-6652.
6. Du TT, Wang L, Duan CL, et al. GBA deficiency promotes CA/α-synSNuclein accumulation through autophagic inhibition by inactivated PPP2A. Autophagy. 2015;11:1803-1820.
7. Uemura N, KoikeM, Ansai S, et al. Viable neuronopathic Gaucher disease model in Medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein. PLoS Genet. 2015;11:e1005065.
8. Awad O, Sarkar C, Panicker LM, et al. Altered TFEB-mediated lysosomal biogenesis in Gaucher disease iPSC-derived neuronal cells. Hum Mol Genet. 2015;24:5775-5788.

1. http://www.neurologyadvisor.com/movement-disorders/gba-variants-predict-rapid-progression-of-parkinsons-disease/article/521295

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Cellular defect may be linked to Parkinson's: study

September 8, 2016

(HealthDay)—Researchers say they've discovered a cellular defect that may be common to all forms of Parkinson's disease.

The defect plays a major role in the die-off of a group of nerve cells whose loss is a hallmark of Parkinson's, according to the Stanford University team. The researchers conducted a series of experiments with cells from Parkinson's patients and healthy people.

"We've found a molecular biomarker that characterizes not just familial cases of Parkinson's, in which a predisposition for the disease is clearly inherited, but also the condition's far more prevalent sporadic forms, for which the genetic contribution is either nonexistent or not yet discovered," said senior author Dr. Xinnan Wang, an assistant professor of neurosurgery.

This defect prevents cells from quickly eliminating their internal power sources (mitochondria) when they wear out. So instead of supplying energy, they start releasing waste, Wang and colleagues explained in a university news release.

The finding could lead to more accurate and earlier diagnoses of Parkinson's, as well as new treatments, the researchers said.

Parkinson's disease, a progressive disorder affecting the nervous system, is marked by tremors, stiffness and loss of balance and coordination. It affects one in every 60 to 70 Americans 65 and older.

The study was published online Sept. 8 in the journal Cell Stem Cell.

More information: The Parkinson's Disease Foundation has more on Parkinson's disease. 

Journal reference: Cell Stem Cell

http://medicalxpress.com/news/2016-09-cellular-defect-linked-parkinson.html