Colorado Neurosurgeon Offers New Technique for PD

Monday September 29, 2014

By Electa Draper

The Denver Post - For Parkinson's disease patients struggling to control tremors, stiffness and abnormal movements,  a surgical procedure called deep brain stimulation  has provided relief —  and a new technique, recently available in Colorado, is gaining ground.

It's a very different patient experience.

In traditional DBS, the patient is awake under local anesthesia during most of the four- to eight-hour brain surgery so he or she  can  help guide the surgical team. Diminished tremors indicate the surgeon is finding the  sweet spot in the brain.

In recent  years, surgeons at about a dozen  U.S. surgical facilities  have been relying instead on improved imaging of the brain during  a typically much-shorter operation of two to three hours. And the patient is asleep.

"Brain surgery is a pretty scary thing to have, and brain surgery while you're awake is even scarier," said Dr. David VanSickle of South Denver Neurosurgery on the Littleton Adventist Hospital campus. 

In both asleep and awake versions of  DBS, a surgeon  implants thin insulated wires, or electrodes, through a small opening in the skull into  targeted areas of the  brain. The wires or leads  deliver  electrical signals  that block the abnormal nerve signals responsible for  the  most debilitating motor symptoms of Parkinson's. It's  done  only after   medication is no longer consistently effective or if it is causing serious side effects.

Electrode  extensions  are passed under the skin of the head, neck and shoulder and connected to a battery-operated device, about the size of a stopwatch, called an implantable pulse generator. 

For a young patient such as Katie Strittmatter, diagnosed with Parkinson's five years ago at age 30,  DBS has restored quality to life and motherhood. She chose "asleep DBS."

"It's incredible," said Strittmatter, the wife of Colorado Rockies catching coordinator Mark Strittmatter. "I was taking 38 pills a day. Now I take three. You would not know if you saw me that I have Parkinson's. I have no sign of tremors."

One side effect of the heavy medication she was taking was interference with sleep. The mother of two children, ages 9 and 11,  was exhausted all the time, she said. DBS has restored more normal sleep, but the procedure  wasn't a snap.

"The recovery was harder than I thought," she said. "It took three weeks. It was really painful."

Strittmatter, who weighed in at 98 pounds at the time of her surgery,  said the battery pack in her chest hurt her at first, as did the 60 metal staples in her head.

"It is brain surgery," she said. "It is  a risk. And it doesn't help with the  non-motor symptoms of Parkinson's."

VanSickle, her surgeon, has been performing DBS for seven years — and doing "asleep DBS" for two years using an MRI,  CT scans of the brain   and a robot the size of a soda can that places the electrodes in the brain.

Fewer than 10 percent of Parkinson's patients undergo DBS, VanSickle said, a number he and other  neurosurgeons say could be higher. 

Awake DBS has been used on roughly 100,000 patients since it was developed in France in 1987, according to Medtronic, a leading supplier of DBS devices. Oregon neurosurgeon Kim Burchiel was the first to use DBS in North America as part of a 1991 clinical trial.  The Food and Drug Administration approved it for tremors associated with Parkinson's disease in 2002.

Burchiel, chair of neurological surgery at Oregon Health and Science University,  developed the new technique of asleep DBS, publishing details of the procedure last year. He predicts it  will become the dominant technique in the near future.

VanSickle said using  advanced real-time imaging   allows the surgical team to verify that they have hit specific targets in the brain. That means that electrodes don't have to be moved around to find the sweet spot.

"We're making this a minimally invasive surgery," VanSickle said. "Fewer hours in the brain is better. A smaller hole in the brain is better. Less bleeding is better. Cheaper is better."

Dr. Steven Ojemann, an associate professor of neurosurgery at the University of Colorado School of Medicine, performs both awake and asleep procedures and finds benefits and disadvantages to both. Each patient presents different challenges, he said.

In asleep DBS, Ojemann uses near-real-time MRI to place the electrodes.

"The main drawback is that you don't have the feedback  from the patient. You're relying on anatomical precision," Ojemann said. "We're not at a stage where we can make the contention that asleep surgery is superior."

The  advantages of DBS have the neurosurgery world buzzing that it could one day be  used to treat many conditions, including obsessive-compulsive disorders, obesity, Alzheimer's disease and some forms of depression.

Electa Draper: 303-954-1276, edraper@denverpost.com or twitter.com/electadraper

http://www.denverpost.com/news/ci_26624398/colorado-neurosurgeon-offers-new-technique-parkinsons-disease

Protein that causes frontotemporal dementia also implicated in Alzheimer's disease

Date:

September 29, 2014

Source:

Summary:

Low levels of the naturally occurring protein progranulin exacerbate cellular and cognitive dysfunction, while raising levels can prevent abnormalities in an Alzheimer's model.

Researchers at the Gladstone Institutes have shown that low levels of the protein progranulin in the brain can increase the formation of amyloid-beta plaques (a hallmark of Alzheimer's disease), cause neuroinflammation, and worsen memory deficits in a mouse model of this condition. Conversely, by using a gene therapy approach to elevate progranulin levels, scientists were able to prevent these abnormalities and block cell death in this model.

Progranulin deficiency is known to cause another neurodegenerative disorder, frontotemporal dementia (FTD), but its role in Alzheimer's disease was previously unclear. Although the two conditions are similar, FTD is associated with greater injury to cells in the frontal cortex, causing behavioral and personality changes, whereas Alzheimer's disease predominantly affects memory centers in the hippocampus and temporal cortex.

Earlier research showed that progranulin levels were elevated near plaques in the brains of patients with Alzheimer's disease, but it was unknown whether this effect counteracted or exacerbated neurodegeneration. The new evidence, published in Nature Medicine, shows that a reduction of the protein can severely aggravate symptoms, while increases in progranulin may be the brain's attempt at fighting the inflammation associated with the disease.

According to first author S. Sakura Minami, PhD, a postdoctoral fellow at the Gladstone Institutes, "This is the first study providing evidence for a protective role of progranulin in Alzheimer's disease. Prior research had shown a link between Alzheimer's and progranulin, but the nature of the association was unclear. Our study demonstrates that progranulin deficiency may promote Alzheimer's disease, with decreased levels rendering the brain vulnerable to amyloid-beta toxicity."

In the study, the researchers manipulated several different mouse models of Alzheimer's disease, genetically raising or lowering their progranulin levels. Reducing progranulin markedly increased amyloid-beta plaque deposits in the brain as well as memory impairments. Progranulin deficiency also triggered an over-active immune response in the brain, which can contribute to neurological disorders. In contrast, increasing progranulin levels via gene therapy effectively lowered amyloid beta levels, protecting against cell toxicity and reversing the cognitive deficits typically seen in these Alzheimer's models.

These effects appear to be linked to progranulin's involvement in phagocytosis, a type of cellular house-keeping whereby cells "eat" other dead cells, debris, and large molecules. Low levels of progranulin can impair this process, leading to increased amyloid beta deposition. Conversely, increasing progranulin levels enhanced phagocytosis, decreasing the plaque load and preventing neuron death.

"The profound protective effects of progranulin against both amyloid-beta deposits and cell toxicity have important therapeutic implications," said senior author Li Gan, PhD, an associate investigator at Gladstone and associate professor of neurology at the University of California, San Francisco. "The next step will be to develop progranulin-enhancing approaches that can be used as potential novel treatments, not only for frontotemporal dementia, but also for Alzheimer's disease."

end text

Story Source:

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

end story_source

Journal Reference:

1  S Sakura Minami, Sang-Won Min, Grietje Krabbe, Chao Wang, Yungui Zhou, Rustam Asgarov, Yaqiao Li, Lauren H Martens, Lisa P Elia, Michael E Ward, Lennart Mucke, Robert V Farese, Li Gan. Progranulin protects against amyloid β deposition and toxicity in Alzheimer's disease mouse models. Nature Medicine, 2014; DOI: 10.1038/nm.3672

end journal_references

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Gladstone Institutes. "Protein that causes frontotemporal dementia also implicated in Alzheimer's disease." ScienceDaily. ScienceDaily, 29 September 2014. <www.sciencedaily.com/releases/2014/09/140929094041.htm>.

Turmeric compound boosts regeneration of brain stem cells

Date:

September 25, 2014

Source:

BioMed Central

Summary:

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer's disease.

A bioactive compound found in turmeric promotes stem cell proliferation and differentiation in the brain, reveals new research published today in the open access journal Stem Cell Research & Therapy. The findings suggest aromatic turmerone could be a future drug candidate for treating neurological disorders, such as stroke and Alzheimer's disease.

The study looked at the effects of aromatic (ar-) turmerone on endogenous neutral stem cells (NSC), which are stem cells found within adult brains. NSC differentiate into neurons, and play an important role in self-repair and recovery of brain function in neurodegenerative diseases. Previous studies of ar-turmerone have shown that the compound can block activation of microglia cells. When activated, these cells cause neuroinflammation, which is associated with different neurological disorders. However, ar-turmerone's impact on the brain's capacity to self-repair was unknown.

Researchers from the Institute of Neuroscience and Medicine in Jülich, Germany, studied the effects of ar-turmerone on NSC proliferation and differentiation both in vitro and in vivo. Rat fetal NSC were cultured and grown in six different concentrations of ar-turmerone over a 72 hour period. At certain concentrations, ar-turmerone was shown to increase NSC proliferation by up to 80%, without having any impact on cell death. The cell differentiation process also accelerated in ar-turmerone-treated cells compared to untreated control cells.

To test the effects of ar-turmerone on NSC in vivo, the researchers injected adult rats with ar-turmerone. Using PET imaging and a tracer to detect proliferating cells, they found that the subventricular zone (SVZ) was wider, and the hippocampus expanded, in the brains of rats injected with ar-turmerone than in control animals. The SVZ and hippocampus are the two sites in adult mammalian brains where neurogenesis, the growth of neurons, is known to occur.

Lead author of the study, Adele Rueger, said: "While several substances have been described to promote stem cell proliferation in the brain, fewer drugs additionally promote the differentiation of stem cells into neurons, which constitutes a major goal in regenerative medicine. Our findings on aromatic turmerone take us one step closer to achieving this goal."

Ar-turmerone is the lesser-studied of two major bioactive compounds found in turmeric. The other compound is curcumin, which is well known for its anti-inflammatory and neuroprotective properties.

end text

Story Source:

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

end story_source

Journal Reference:

1  Joerg Hucklenbroich, Rebecca Klein, Bernd Neumaier, Rudolf Graf, Gereon Fink, Michael Schroeter, Maria Rueger. Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Research & Therapy, 2014; 5 (4): 100 DOI: 10.1186/scrt500

end journal_references

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BioMed Central. "Turmeric compound boosts regeneration of brain stem cells." ScienceDaily. ScienceDaily, 25 September 2014.

http://www.sciencedaily.com/releases/2014/09/140925205819.htm

WEARING OFF IN PARKINSON'S DISEASE

28th September 2014 - New research

Parkinsonism Related Disorders [2014] 20 (2) : 204-211 (F.Stocchi, A.Antonini, P.Barone,
M.Tinazzi, M.Zappia, M.Onofrj, S.Ruggieri, L.Morgante, U.Bonuccelli, L.Lopiano, P.
Pramstaller, A.Albanese, M.Attar, V.Posocco, D.Colombo, G.Abbruzzese)
Complete abstract : http://www.ncbi.nlm.nih.gov/pubmed/24275586
Wearing off of the effect of drugs for Parkinson's Disease has been found to occur far earlier
and in more people with Parkinson's Disease than previously assumed. Wearing off is very
individual and there is no standard time frame for when this may occur or which symptoms
are experienced. For more information go to :
http://www.epda.eu.com/en/parkinsons/in-depth/medication/wearing-off/wearing-off-symptoms/
Neurologists found that there was wearing off in 57% of
people with Parkinson's Disease. However, when this was
assessed by the patients themselves, there was found to be
wearing off in 67% of people with Parkinson's Disease. Even
in people who had Parkinson's Disease for less than 2.5 years
there was wearing off in 21% of people when assessed by
neurologists and in 41% when patients assessed themselves.
The most frequent wearing off symptoms were slowness of
movements (55%) and reduced dexterity (48%). Those
factors most associated with wearing off were : younger age,

female gender, severer symptoms, and duration of treatment.
Wearing Off is already common in the early stages of Parkinson's Disease
 and is underestimated by routine neurological clinical evaluation. 
The effect of Parkinson's Disease drugs is therefore often relatively short lived.



http://www.viartis.net/parkinsons.disease/news/140928.pdf
mail@viartis.net

Ali, Brown reunite years after Ali’s legal fight

Jim Brown, left, and Bill Russell, right, stand behind Muhammad Ali before the Ali Humanitarian Awards ceremony Saturday, Sept. 27, 2014, in Louisville, Ky. The two were participants of the Ali Summit in 1967, and Brown is in Louisville to receive the the Muhammad Ali Humanitarian Lifetime Achievement Award. (Timothy D. Easley/Associated Press)

By Associated Press September 27 at 8:31 PM

LOUISVILLE, Ky. — Muhammad Ali was on the ropes for refusing induction into the Army, and Jim Brown wanted to help. But first, the NFL great wanted to hear the boxing champion’s reasons for not answering the call to military service during the Vietnam War.

So Brown led a group of prominent black athletes who hit Ali with a flurry of questions during a two-hour meeting in Cleveland in June 1967. Ali didn’t duck the questions and stuck to his principles, citing his religious beliefs in refusing to join the military.

The dozen athletes, including Bill Russell and Kareem Abdul-Jabbar, emerged from the meeting to publicly support Ali at a time when the champ was one of the country’s most polarizing figures.

“People got the answers that they wanted,” Brown recalled Saturday.

Nearly 50 years after the meeting, now known as the “Ali Summit,” several participants including Brown and Russell were at Ali’s side again Saturday night in the boxing champ’s hometown. Brown received a lifetime humanitarian achievement award bearing Ali’s name.

While posing for photos with the 72-year-old Ali, Brown leaned over and whispered to the seated former heavyweight champion. Later, Brown said he told Ali: “You’re the greatest of all time.”

The lineup of Muhammad Ali Humanitarian Award winners included Academy Award-winning actress Susan Sarandon and Grammy Award-winning hip-hop artist Common. Other award winners included a half-dozen young adults from around the world honored for their humanitarian roles.But much of the spotlight was on that meeting decades ago in Cleveland when Ali, was at his most vulnerable, and how the group of athletes joined Ali’s corner in the fight of the champ’s life. Several participants met at the Muhammad Ali Center a few hours before the awards event Saturday night. Ali, who is battling Parkinson’s disease, met the group shortly before the awards show at a downtown hotel.

“No one had really sat down and listened to him and given him the respect of having him tell his point of view,” Brown said in recalling the 1967 meeting.

Former NFL player John Wooten, another meeting participant, said Ali’s questioners “came at him with everything.” The man known for his brashness in the ring was humble when explaining his reasons, he said.

It was enough to win over another participant, former NFL player Bobby Mitchell.

“I came there ready to try to talk him into going into the service,” Mitchell said Saturday. “I actually felt that way. He whipped my behind pretty quick, because he can talk. But when it was all over, I felt good about walking out of there saying, ‘We back him.’”

Ali was stripped of his world heavyweight boxing title in 1967 while in his prime and was convicted of draft evasion. Ali found himself embroiled in a legal fight that ended in 1971, when the U.S. Supreme Court ruled in his favor.

Ali regained the heavyweight title in 1974, defeating George Foreman in the “Rumble in the Jungle.” A year later, he outlasted Joe Frazier in the epic “Thrilla in Manila” bout. Ali’s last title came in 1978 when he defeated Leon Spinks.

Long before Ali became an icon, the meeting’s participants were taking a risk by throwing their support behind him.

“It was the United States government that we were dealing with,” Brown said Saturday. “Careers were at stake. And everybody that showed up at that meeting put all of that on the line. That was heavyweight stuff.”

Russell, who pulled up a decades-old photo of himself and Ali on his smartphone, said the legal battle came down to citizenship rights. Russell had known Ali for years and never doubted his sincerity when citing his reasons for refusing military service. Russell said the legal fight transformed Ali.

“He became a hero to a lot of young folks in this country, black and white,” the basketball great said. “Because what he was talking about was citizenship. And my citizenship, or Jim’s ... is not a gift from other citizens. It’s a right of birth.”

Brown, an outspoken civil-rights advocate who remains active in efforts to stem violence, improve education and uplift neighborhoods, said he didn’t want to compare the role of athletes today and in his era.

“I’m here to motivate as many people as I can in this country to take a look at the violence ... and the inferior education that a lot of our kids are getting,” he said.

Former NFL star Ray Lewis, who joined the players from a previous generation Saturday, said Ali’s principles still resonate with young people today.

“He did stand for something, and that something changed generations of young men, realizing that we all have a true freedom, a true opportunity to do what you’re going to do, say what you’re going to say,” he said. “And if you believe strongly in something, truthfully in your heart, follow it.”

MJFF Drives Conversation around Payment for Parkinson’s Care

FoxFeed Blog

Posted by  Maggie McGuire, September 26, 2014

We work so hard trying to get Parkinson’s medications developed and through the phases of clinical testing, that it’s easy to think of the finish line as approval by the U.S. Food and Drug Administration. Truthfully, though, they’re not the only ones who decide if drugs make their way to patient hands.

Payers (insurance companies and Medicaid and Medicare) play a role not only in helping patients get the therapies they need but also in encouraging drug companies to invest in developing new drugs.

A survey of biotech CEOs revealed that the biggest perceived threat for successful product development is no longer regulatory review but insurance coverage and reimbursements. Biotech companies trying to lure bigger partners who can help them advance promising projects are frequently asked to demonstrate commercial potential.

“At The Michael J. Fox Foundation we de-risk the Parkinson’s research field to make it more attractive to companies and investors who can create the treatments patients need,” said Lona Vincent, senior associate director of research partnerships. “Part of that is brokering conversations about the payer environment and what payers are looking for so that we can help companies design studies with the greatest potential for payer coverage.”

Last month MJFF welcomed more than 20 payers and policymakers from the neurology field to discuss what was important in evaluating Parkinson’s treatments for coverage or reimbursement. The Foundation also included physicians and a member of our Patient Council to offer education in the other direction: what outcomes people with Parkinson’s value and should be weighed in payers’ decisions.

“Our patient guest shared an impactful perspective on how his Parkinson’s symptoms affect daily activities that many of take for granted,” said Annesha White, who co-led the meeting and serves as assistant to the MJFF CEO. “The payers all agreed that it resonated with them, and they would be interested to hear more about those kinds of experiences from the patient perspective.”

We’ll continue to engage with payers to represent the patient voice and to gather information that can help inform trial design. We may need your help in collecting opinions and experiences to share. So if we email or ask on our social channels for a survey response, we hope you’ll contribute to our knowledge base. Know your input helps us in our efforts to move closer to a cure.

https://www.michaeljfox.org/foundation/news-detail.php?mjff-drives-conversation-around-payment-for-parkinson-care