Unwanted formation of blood vessels (angiogenesis) in the brain is likely to be the cause of intractable walking and balance difficulties for people who suffer from Parkinson's disease. This conclusion is supported by new research from Lund University in Sweden.
Many people with Parkinson's disease eventually experience walking and balance difficulties, despite adequate medication. Moreover, some patients cannot fully take dopamine-based medication, as dopamine can lead to side effects.
The current research findings verify similar data from a previous study by other researchers, which was performed on brain tissue from a small number of deceased patients.
"The strength of our study is the number of participants, and the fact that they are alive. Because many suffer from several parallel diseases at the final stage of their lives, it is difficult to analyse samples from deceased persons," explains Oskar Hansson, reader at Lund University and consultant at Skåne University Hospital.
The findings, published in the journal Neurology, were made when the researchers used a broad approach when looking for mechanisms to increase understanding of how Parkinson's disease works. "The measurements showed clear connections between markers of angiogenesis in the brain and walking or balance difficulties among the participants. We also noted an increased permeability of the blood-brain barrier, which leads to blood components potentially leaking into the brain and causing damage," says Oskar Hansson. The first part of the study included 100 Parkinson's patients and 38 healthy control persons at Skåne University Hospital in Malmö. Through a cerebrospinal fluid sample, several different proteins that indicate formation of blood vessels in the brain were measured. To ensure the results, two additional groups of patients of approximately the same size were also tested.
"Medication for angiogenesis already exists. If we can confirm our results in further studies, these drugs can be tested on Parkinson's patients in the future," says Oskar Hansson.
Before it may be time to test the drugs in clinical studies, Oskar Hansson and his colleagues plan on conducting an animal study, to gain further knowledge about the mechanisms that are believed to cause problems for Parkinson's patients, and to enable a selection of the most appropriate drugs to use.
As a live TV audience watches, a neurosurgery team at UH Case Medical Center in Cleveland will perform an operation that has helped many Parkinson’s disease patients get significant relief from their debilitating symptoms—tremors, rigidity, stiffness, slowed movements and difficulty walking—and also enabled them to reduce their amount of medication.
Deep Brain Stimulation, or DBS, was pioneered as a Parkinson’s treatment by Dr. Alim-Louis Benabid, a neurosurgeon who also possessed a Ph.D. in physics. In the 1980s, patients were treated by surgically destroying parts of their brains where tremors originated, or using medication with unpleasant side-effects. In 1987, Benabid was performing a surgery using the then-standard method of burning away brain tissue with an electrode. As he tested various regions with electrical pulses, Benabid wondered what would happen if he used different frequencies. To his surprise, he found one that suppressed the patient’s tremor. "I thought, aha, this might be the solution," he later recalled in a 2010 Lancet article.
Dr. Benabid’s inspiration led to the development of implantable DBS devices to provide patients’ brains with continual stimulation, which were approved by the U.S. Food and Drug Administration for use in treating Parkinson’s symptoms in 2002. Since then, thousands of patients have received DBS, and there are numerous surgical centers in the U.S. that perform the operation. While DBS initially was used as a last resort for the most severely-disabled patients, by the mid-2000s, doctors were using it to help patients with moderate symptoms, after they were unable to control the disease with medication.
Getting DBS is a complex process. Patients generally remain awake during the procedure so that surgeons can communicate with them and do neurological tests along the way and make sure the hardware is implanted in the right place. According to a primer published by the National Parkinson Foundation, the first step is to inject local anesthesia into a patient’s scalp, and then use screws to attach the patient’s head to a box-like frame that helps to guide neurosurgeons more precisely to the target. Then, the surgical team scans the patient’s brain with magnetic resonance imaging (MRI) or computed tomography (CT) to create a roadmap for the operation.
Once the team knows where they want to target, the patient’s scalp is injected with more anesthetic. Then a neurosurgeon uses a drill to bore a dime-sized hole in the patient’s skull. Then, the doctors insert a thin wire with four electrical contacts at its tip into one of several brain areas—the globus pallidus internus, the thalamus, or the subthalamic nucleus—that control movement.At that point, the really delicate work begins. As electrical current is passed through the wire in the patient’s brain, the surgical team asks the patient to move his or her face, arm, or leg, or else moves them. They’re monitoring all of that activity with a computer, in an effort to pinpoint the exact spot where the tiny wire needs to be. Since surgeons are dealing with the brain structures that may only be a few millimeters in length, there’s precious little room for error.
After they’ve found the spot, they connect the wire to an external generator, and give the patient more stimulation to gauge the effect it is having on the Parkinson’s symptoms. Once they’ve confirmed that it is in the right place, they fasten it in place and then seal the hole in the skull and scalp with a plastic cap and stitches. The length of the surgery varies from hospital to hospital, but it often lasts as long as six hours.
After that—either immediately, or in a few days—a second procedure is performed, in which the wiring in the brain is attached through a patient’s neck to a pacemaker-like device called a neurostimulator, which they implant in the patient’s chest, just below the collarbone. When the device is turned on, it delivers electrical stimulation to the brain.
Exactly how DBS reduces Parkinson’s symptoms in some patients is not yet completely understood. One theory is that the electrical pulses given off by the DBS device stimulate neurons to fire, which makes them too busy to transmit the abnormal electrical signals triggered by the disease. But that hasn’t been proven, and scientists are at a loss to explain exactly why DBS works better for some patients than others.
Researchers continue to work to improve DBS in hopes of making it more effective. UH Case Medical Center’s team will utilize a digital visualization product created by a Cleveland-based company called Surgical Theater, headed by a former Israeli air force officer who once created flight simulators for fighter pilots. The simulator allows surgeons to create and explore 3D-models of patients’ brains. As an article in Crain’s Cleveland Business reports, Case surgeons also are interested in using Oculus Rift virtual reality headsets in the operating room, so that they can use the simulations to help guide an operation.
Meanwhile, medical researchers are looking at DBS to treat other brain illnesses, such as obsessive-compulsive disorder and treatment-resistant depression. So that operation which viewers will watch on “Brain Surgery Live” is one that could become increasingly common in the future.
A drug that's already approved for treating leukemia appears to dramatically reduce symptoms in people who have Parkinson's disease with dementia, or a related condition called Lewy body dementia.
A pilot study of 12 patients given small doses of nilotinib found that movement and mental function improved in all of the 11 people who completed the six-month trial, researchers reported Saturday at the Society for Neuroscience meeting in Chicago.
And for several patients the improvements were dramatic, says Fernando Pagan, an author of the study and director of the Movement Disorders Program at Georgetown University Medical Center. One woman regained the ability to feed herself, one man was able to stop using a walker, and three previously nonverbal patients began speaking again, Pagan says.
"After 25 years in Parkinson's disease research, this is the most excited I've ever been," Pagan says.
f the drug's effectiveness is confirmed in larger, placebo-controlled studies, nilotinib could become the first treatment to interrupt a process that kills brain cells in Parkinson's and other neurodegenerative diseases, including Alzheimer's.
One of the patients in the pilot study was Alan Hoffman, 74, who lives with his wife, Nancy, in Northern Virginia.
Hoffman was diagnosed with Parkinson's in 1997. At first, he had trouble moving his arms. Over time, walking became more difficult and his speech became slurred. And by 2007, the disease had begun to affect his thinking.
"I knew I'd dropped off in my ability to read," Hoffman says. "People would keep giving me books and I'd have read the first chapter of about 10 of them. I had no ability to focus on it."
"He had more and more difficulty making sense," Nancy Hoffman says. He also became less active, less able to have conversations, and eventually stopped doing even household chores, she says.
But after a few weeks on nilotinib, Hoffman "improved in every way," his wife says. "He began loading the dishwasher, loading the clothes in the dryer, things he had not done in a long time."
Even more surprising, Hoffman's scores on cognitive tests began to improve. At home, Nancy Hoffman says her husband was making sense again and regained his ability to focus. "He actually read the David McCullough book on the Wright brothers and started reading the paper from beginning to end," she says.
The idea of using nilotinib to treat people like Alan Hoffman came from Charbel Moussa, an assistant professor of neurology at Georgetown University and an author of the study.
Moussa knew that in people who have Parkinson's disease with dementia or a related condition called Lewy body dementia, toxic proteins build up in certain brain cells, eventually killing them. Moussa thought nilotinib might be able to reverse this process.
His reasoning was that nilotinib activates a system in cells that works like a garbage disposal — it clears out unwanted proteins. Also, Moussa had shown that while cancer cells tend to die when exposed to nilotinib, brain cells actually become healthier.
So Moussa had his lab try the drug on brain cells in a petri dish. "And we found that, surprisingly, with a very little amount of the drug we can clear all these proteins that are supposed to be neurotoxic," he says.
Next, Moussa had his team give the drug to transgenic mice that were almost completely paralyzed from Parkinson's disease. The treatment "rescued" the animals, he says, allowing them to move almost as well as healthy mice.
Moussa's mice got the attention of Pagan from Georgetown's Movement Disorders Program. "When Dr. Moussa showed them to me," Pagan says, "it looked like, hey, this is type of drug that we've been looking for because it goes to the root of the problem."
The pilot study was designed to determine whether nilotinib was safe for Parkinson's patients and to determine how much drug from the capsules they were taking was reaching their brains. "But we also saw efficacy, which is really unheard of in a safety study," Pagan says.
The study found that levels of toxic proteins in blood and spinal fluid decreased once patients began taking nilotinib. Also, tests showed that the symptoms of Parkinson's including tremor and "freezing" decreased. And during the study patients were able to use lower doses of Parkinson's drugs, suggesting that the brain cells that produce dopamine were working better.
But there are some caveats, Pagan says. For one thing, the study was small, not designed to measure effectiveness, and included no patients taking a placebo.
Also, nilotinib is very expensive. The cost of providing it to leukemia patients is thousands of dollars a month.
And finally, Parkinson's and dementia patients would have to keep taking nilotinib indefinitely or their symptoms would continue to get worse.Alan Hoffman was OK for about three weeks after the study ended and he stopped taking the drug. Since then, "There's (been) a pretty big change," his wife says. "He does have more problems with his speech, and he has more problems with cognition and more problems with mobility."
The Hoffmans hope to get more nilotinib from the drug's maker, Novartis, through a special program for people who improve during experiments like this one.
Meanwhile, the Georgetown team plans to try nilotinib in patients with another brain disease that involves toxic proteins: Alzheimer's.
Institute of Neurosciences of Apollo Hospitals, Bangalore, have started providing Deep brain stimulation (DBS), to patients with Parkinson’s disease and various other movement disorders. Parkinson’s disease, one of the commonest neurodegenerative disorders, whose prevalence has been increasing with increased life expectancy. Currently millions of people are suffering from Parkinson’s disease world wide and off late it is being commonly recognized in India too.
Unlike various other disorders, Parkinson’s disease has good therapeutic options to improve the quality of life. In April 2014, Apollo Hospitals, had launched exclusive Parkinson’s disease and Movement disorders clinic. This clinic is being run by Dr. Prashanth LK. Dr. Prashanth LK, is a neurologist, who is further specialized in Parkinson’s disease and other movement disorders. After successive launch of the clinic, they have recently conducted a first Deep Brain stimulation (DBS) procedure. The procedure involves installing a specialized stimulation device in the brain similar to cardiac pacemaker, which tries to modulate the brain functions. The surgery was conducted by Dr. Arun Naik and team. According to the Neurosciences team, DBS is a very effective therapy for patients with moderately advanced Parkinson’s disease, where in benefit of medications are limited by its side effects. The surgery is currently well approved therapy for Parkinson’s disease world wide and currently forms the standard of care in Parkinson’s disease therapeutic armamentarium.
New University of Michigan research finds people with Parkinson's disease may want to consider attempting to do the dishes, fold the laundry and take strolls around the neighborhood in their quest to control their symptoms.
Parkinson's patients often become sedentary because of motor symptoms such as gait, balance problems or falls, said study principal investigator Nicolaas Bohnen, M.D., Ph.D., director of the U-M Functional Neuroimaging, Cognitive and Mobility Laboratory.
Once patients feel unstable on their feet, they may develop a fear of falling and then get scared to do any activity at all. Bohnen's team investigated whether participation in exercise, like swimming or aerobics, could help alleviate the motor symptoms that made these patients want to stay sedentary in the first place.
"What we found was it's not so much the exercise, but the routine activities from daily living that were protecting motor skills," Bohnen said. "Sitting is bad for anybody, but it's even worse for Parkinson's patients."
The imaging study, now available online in Parkinsonism and Related Disorders, was conducted by U-M faculty who hold appointments in both radiology and neurology.
Researchers investigated the relationship between the duration of both non-exercise and exercise physical activity and motor symptom severity for 48 Parkinson's disease patients over a 4-week period. They performed PET brain imaging to measure dopamine levels and used a questionnaire to learn about how physically active the patients were, including both exercise and non-exercise activity. They found that non-exercise physical activity was linked to less severe motor symptoms.
Although loss of dopamine is a key brain change for Parkinson's patients, and has been thought to be the main reason why Parkinson's patients become more sedentary, the researchers found non-exercise physical activity protected motor skills even among patients with differing levels of dopamine.
"This may have a big impact for Parkinson's patients," said co-author Jonathan Snider, M.D., clinical lecturer of neurology at the University of Michigan. "Not only worsening Parkinsonism but also increasingly sedentary behavior may explain more severe motor symptoms in advanced Parkinson's disease."
"I tell my patients to stand up, sit less, and move more," said Bohnen, also professor of radiology and neurology at the University of Michigan, VA Ann Arbor Healthcare System staff physician and investigator in U-M's Udall Center for Excellence in Parkinson's Disease Research.
The above post is reprinted from materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.
Jonathan Snider, Martijn L.T.M. Müller, Vikas Kotagal, Robert A. Koeppe, Peter J.H. Scott, Kirk A. Frey, Roger L. Albin, Nicolaas I. Bohnen. Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration. Parkinsonism & Related Disorders, 2015; DOI: 10.1016/j.parkreldis.2015.08.027
we petition the obama administration to: Dystonia is the third most common movement disorder but remains largely unknown to the public. Dystonia is a neurological disorder characterized by involuntary muscle contractions causing abnormal, often repetitive, movements and/or postures.
Symptoms may impede the ability to walk (as in generalized dystonia or foot/leg dystonia), control the posture of the head (as in cervical dystonia), speak (as in spasmodic dysphonia or oromandibular dystonia), see (as in blepharospasm), and/or write (as in hand dystonia). Many individuals experience debilitating pain. There are numerous manifestations of dystonia, affecting people of all ages and backgrounds. Individuals are frequently misdiagnosed, which delays access to appropriate medical care and community support.