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Deep Brain Stimulation for Parkinson Disease

This article appeared in the Spring 2018 issue of The Network magazine.

Deep brain stimulation (DBS) is an advanced therapy for patients with Parkinson disease (PD) suffering from complications of carbidopa/levodopa treatment. It has been FDA approved for use in PD since 2002 and for tremor prior to that. DBS involves the surgical implantation of a device with electrodes that deliver electrical signals to specific areas within the brain. Once the electrodes are placed, they are then connected to an implanted pulse generator (battery) which is placed under the skin, typically in the chest. When the device is activated, it delivers regular electrical pulses to that area of the brain and results in improvement of PD symptoms. The exact mechanisms of how DBS improves symptoms are not known. However, we do know that it disrupts pathological signals that occur within the brain of PD patients.

Currently, DBS is approved for those patients with a diagnosis of idiopathic PD, who have had symptoms for four or more years and suffer from motor complications that are not controlled with medications. Motor complications refer to the medications not lasting as long (wearing off), levodopa induced dyskinesias (extra, abnormal and involuntary movements) and dose failures.

Individuals who would not benefit from DBS are those with atypical forms of PD, those with signs of dementia and those whose symptoms do not improve with levodopa. Depression and anxiety do not preclude someone from receiving DBS, but these should be addressed, treated and well controlled prior to proceeding.

The process of implanting DBS for patients is a lengthy process. It involves careful pre-surgical screening, two or three surgeries and many follow up programming appointments. The first step is what is called an “Off/On Test.” For this test, the patient comes to an appointment with the neurologist after not taking PD medications from the night before. The patient is then examined in this “Off” medication state. Then, the patient receives a higher than usual dose of carbidopa/levodopa and then re-examined once those take effect.

The next step is to have a formal neuropsychological evaluation performed. This evaluation typically takes about a half of a day and includes extensive testing of memory, language and other cognitive abilities. Once these two preliminary evaluations are complete, most DBS centers hold a multi-disciplinary case conference to discuss these results and the patient’s candidacy for DBS surgery. If there are no contraindications to surgery, the patient will meet with the neurosurgeon who reviews the procedure and the potential risk of surgery. Often times, an additional pre-operative medical evaluation is also required to screen for other medical conditions that could pose additional surgical risks or potential complications. The patient also receives a pre-surgical MRI of the brain to assist with placement of the DBS electrodes.

Most centers perform DBS implantation in two or three individual surgeries. After the DBS device is implanted, the patient then returns to the clinic to turn the device on, typically after three or four weeks. The number of programming appointments needed varies from one patient to the next but can take 6-12 months to reach optimal settings. The battery is checked at routine follow-up appointments and depending on which device is implanted, the battery will need to be replaced from time to time.

Not all symptoms of PD will improve from DBS therapy. The general rule of thumb is if particular symptoms improve after taking carbidopa/levodopa then those symptoms can be expected to improve with DBS. The caveat to this rule are refractory tremors. Tremor in PD can often be resistant to carbidopa/levodopa, but responds well to DBS. In addition, DBS can significantly reduce problems with medication wearing off and dyskinesias. Walking difficulties in PD can be varied and complex. Some of these may respond to DBS but many do not, including balance. Therefore, patients should consult with their DBS physician prior to surgery in regard to their specific walking issues.

Symptoms that are unlikely to improve with DBS are those symptoms that worsen with levodopa, balance, memory problems, speech and swallowing difficulties. DBS can also allow the reduction of some of the PD medications, although it is not realistic to expect to stop all PD related medications after surgery.

It is important to understand that DBS is not a cure however, it is very effective at treating many motor symptoms of PD and improving quality of life.

Ryan T. Brennan, D.O. is an assistant professor in the Department of Neurology at Medical College of Wisconsin.

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New Reports Measure Parkinson’s Motor Progression

Two recent papers outline the progression of Parkinson’s disease (PD) movement or motor symptoms in distinct study populations. While these findings do not provide an absolute picture of how one person will progress with PD, the results may help researchers design smaller, faster and less expensive clinical trials of new treatments.

Changes in Early Parkinson’s and with Dopamine Therapy

The Parkinson’s Progression Markers Initiative study, sponsored by The Michael J. Fox Foundation (MJFF), reported on changes in motor symptoms over five years from people who joined the study early in their disease (within two years of diagnosis). The largest change (as measured by the Unified Parkinson’s Disease Rating Scale or UPDRS) came in the first year, then symptoms plateaued as people began taking dopamine medication.

Many studies of therapies that aim to slow or stop disease progression recruit people in similar early stage of disease. Understanding what to expect over the first year and as those study participants begin dopamine medication can help drug developers design their trials.

Read the full paper.

Slower Progression in G2019S LRRK2 Mutation Carriers

Analysis from the LRRK2 Ashkenazi Jewish Consortium — part of the MJFF-supported LRRK2 Cohort Consortium — compared progression in people who carry the G2019S mutation in the LRRK2 gene, a leading genetic cause of Parkinson’s disease, to progression in people without a known cause of their disease (so-called sporadic PD).

People in the study who carried a G2019S LRRK2 mutation advanced 30 percent more slowly on the UPDRS than people with sporadic PD. The authors from Mount Sinai Beth Israel Medical Center in New York noted, though, that they could not confirm whether those results were from a subgroup with less severe disease bringing down the average or if most G2019S LRRK2 mutation carriers have less aggressive disease.

It is not to say, either, that if you do not carry this genetic mutation you will definitely progress quickly; Parkinson’s is a highly variable disease.

The results are already helping companies testing therapies against LRRK2 dysfunction. Carole Ho of Denali Therapeutics, which brought the first LRRK2 drug into clinical trials late last year, told research news website AlzForum, “We are using the new data to design trials to test LRRK2 inhibitors. Knowing the natural course of disease is very important.”

Read more on these results.

PPMI is recruiting people of Ashkenazi Jewish descent with a Parkinson’s or Gaucher disease connection. Learn more about the study.

 

Article from Michael J. Fox Foundation for Parkinson’s Research.

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Could caffeine in the blood help diagnose Parkinson’s?

Blood caffeine levels could be promising diagnostic biomarkers for early-stage Parkinson’s, Japanese researchers reported in the journal ‘Neurology’ earlier this month.

The study found that people with Parkinson’s had lower levels of caffeine and caffeine metabolites in their blood than people without the disease, at the same consumption rate.

Caffeine concentrations also were decreased in Parkinson’s patients with motor fluctuations than in those without Parkinson’s. However, patients in more severe disease stages did not have lower caffeine levels.

The study’s authors, Dr David Munoz, University of Toronto, and Dr Shinsuke Fujioka, Fukuoka University, suggested that the “decrease in caffeine metabolites occurs from the earliest stages of Parkinson’s.”

They added: “If a future study were to demonstrate similar decreases in caffeine in untreated patients with Parkinson’s […] the implications of the current study would take enormous importance.”

 

Article from Parkinson’s Life.

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Duopa device among newer treatments for Parkinson’s disease

Until August, Kern Jackson avoided going out in public.

Parkinson’s disease had progressed far enough that the levadopa pills he’d taken since 2008 weren’t as reliable to ease the symptom of his muscles freezing up. In the past two years, he had to take the medicine more frequently as it wore off quickly, leaving him unable to move.

“I was taking pills every two hours, and during the night,” said Jackson, 70, a retired physician who lives in Medical Lake. “It would take 20 to 45 minutes to be effective, then I’d be moving normally for about an hour. It was hard to plan to do anything.”

So in August, Jackson chose to get a newer Duopa device through Dr. Jason Aldred, a neurologist at Northwest Neurological. The Spokane clinic partners with Inland Imaging, where patients go in for an outpatient procedure to make a small incision in the stomach wall and insert a tube in the small intestine.

The external Duopa device has a pump for continuous delivery via the tube of a levadopa gel, contained in a medication cartridge that patients reload once a day into the device.

According to Aldred, the Duopa device first became available in 2015 after U.S. Food & Drug Administration approval, and it’s among a couple of newer developments for Parkinson’s treatment. The clinic also is participating in two clinical research trials that are attempting to slow disease progression.

The day after his outpatient procedure, Jackson saw Aldred at Northwest Neurological to program the system’s medicine dosage. Clinic staff observed Jackson’s movements for a day during office hours to make sure the new system was syncing correctly for his ability to get around.

Jackson now wears the device in a belted pack around his waist, and he said it’s helped him be more active. He and his wife, Diana, have since traveled by airplane and walked on the Centennial Trail.

“I feel much more confident going somewhere,” Jackson said. “I just went to a men’s retreat in Idaho with my son-in-law, and things went well.”

Although estimates vary, about 1 million people in the U.S. live with the disease, according to the Parkinson’s Foundation. Symptoms include tremor, rigidity, extreme slowness of movement and impaired balance.

Levadopa, now used for more than 50 years to treat Parkinson’s, is often considered the most effective for treatment of motor symptoms.

“Levadopa is turned into dopamine in the brain and replaces dopamine,” Aldred said “That’s huge because dopamine is the natural chemical in the brain that’s low in Parkinson’s patients, so we literally have the ability to replace something that’s low to bring about remarkable improvement in movement, stiffness and tremor.

“However, it doesn’t slow the progression. It treats symptoms remarkably for years or decades. Parkinson’s progresses slowly, but it does progress, and it can cause horrible quality of life issues.”

The Duopa device is offered as a choice for some patients with moderate to advanced Parkinson’s if levadopa in a pill form becomes less reliable, Aldred said. Other patients might be candidates for deep brain stimulation, a therapy that’s been around since 1997, he said.

“As the disease advances for moderate to advanced Parkinson’s, the medicine kicks in and wears off,” said Aldred, adding that also long-term, the disease affects other nerves outside of the brain including in the stomach, so medicine is less effectively moved into the small intestine for absorption.

“We call it dose failure,” he said. “That’s actually a big problem; the medicine is sitting in the stomach and doesn’t move. With the Duopa device, the tube mechanically bypasses the stomach and goes into the small intestine, and the medicine is released physically past the stomach.”

Aldred said the Duopa device is new enough that, so far, just over 30 of its clinic patients have one.

“This is a very new treatment and largely people are slow to warm up to it,” he said, adding that some people might have a stigma about having a tube inserted, a procedure that’s sometimes associated with end-of-life issues.

The small amount of tubing that’s external is flexible, Aldred said, and it’s hidden often under clothing. It can be disconnect for up to two hours if needed.

However, Aldred said current treatments, including Duopa, only partially relieve symptoms, so the two research trials are attempting approaches that might slow or stop the disease’s progression.

Both trials are seeking to stem what is thought to damage cells in the brain that regulate behavior, cognition and movement. A main research focus is finding a way to stop or clear out Lewy bodies, which are abnormal aggregates of protein that develop inside nerve cells in Parkinson’s.

“We have some interesting, cutting-edge NIH, Michael J. Fox Foundation-affiliated clinical research trials,” Aldred said.

One is a vaccine trial using anti-bodies in an attempt that might prevent the spread of Lewy bodies in the brain. A second phase of that study started this month involving a handful of clinic patients.

The other trial will test Nilotinib, a FDA-approved medicine used in treatment for a form of leukemia, but with a fraction of the dose applied for patients with mild Parkinson’s.

“This is a medication that may enhance the clearing of Lewy Bodies from the brain that we think is destructive,” Aldred added.

“We’re trying to get to the point before it spreads,” he said. “That’s a novel way of treating Parkinson’s. These two trials if they’re proven to work, which they haven’t been yet, may be safe and effective ways to slow the disease progression or potentially halt the disease progression.”

There’s also a new device that came out this year for deep brain stimulation, Aldred said. “It was developed by St. Jude’s Medical (since acquired by Abbott). We can aim the electrical current more precisely in the brain to get better effect.”

The DBS treatment requires surgery to implant a wire with four electrodes that deliver an electrical current in the brain to regulate abnormal impulses and smooth out “on time” and “off time” experienced by patients as the impact of medication rises and falls.

The DBS treatment and the Duopa device haven’t been studied head to head on whether one is more effective than the other, Aldred said.

“If someone has moderate cognitive issues, we’d never want to do DBS,” he said.

Alternatively, he added that the Duopa device might be a choice for some patients who aren’t comfortable with DBS.

“I tell patients this is a heavy diagnosis, but there is lot we can do, and one of the things is exercise, ” said Aldred, who encourages physical therapy and regular exercise to maintain better movement and quality of life.

 

Article from The Spokesman-Review.

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Taylor Finseth, MD joins WPA’s Medical Advisory Committee

We are pleased to welcome Taylor Finseth, MD, Aurora Health Care to our Medical Advisory Committee.

Dr. Finseth provides management of movement disorders including Parkinson disease, tremor, dystonia, restless legs and deep brain stimulation programming and performs botox injections for dystonia, chronic migraine and other conditions, as well as treating memory loss. He earned his medical degree at The Ohio State University College of Medicine, Columbus, OH, and completed both his residency in Neurology and fellowship in Movement Disorders at the University of Colorado, Aurora CO. He is board certified by the American Board of Psychiatry and Neurology.

The Medical Advisory Committee provides medical oversight for WPA. The members advise our board and staff on the content of medically-related programs, and on topics related to clinical care of people with Parkinson disease. The Committee consists of doctors from various healthcare locations around the state of Wisconsin.

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6 of the Best Apps for Chronic Illness Management

Managing a chronic illness can be difficult. There are many different medications to take (often at different times), appointments to remember, symptoms to keep track of, and lots of information to absorb. Thankfully, living in a digital age means that there are numerous mobile apps that can help you manage your chronic illness.

We’ve put together a list of some of the best mobile apps for managing your chronic illness:

Medisafe is an app that helps patients manage medications. It helps with dosage and reminds you when you need to take your meds, increasing adherence rates. The information can also be shared with your healthcare team and pharmacy.

Pain Diary works for anyone with a chronic illness. It allows patients to chart and score pain as well as record and track other symptoms of the disease such as fatigue and mood swings. This app also has a feature where patients can connect with others living with the same chronic illness and swap best practices.

ZocDoc is a handy app if you’ve recently been diagnosed with a chronic illness, since one of the first things you’ll need to do is find a doctor to treat you. ZocDoc allows you to search for local specialist doctors who are approved by your insurance company. The app will even tell you when the doctor is available to see you.

My Medical Info is an app that stores all your relevant health history and insurance details. This makes filling out those endless forms a little less challenging, since you won’t have to rely on your memory for all the details. The app will also allow you to program in doctors’ appointments and all the medications you’re taking.

Fooducate helps you keep track of your diet and make healthy choices. Eating well is an integral part of managing any chronic illness and this app will help you to eat the right foods and get you to a healthy body weight. You can program in how many calories you want to consume a day and then add in the food choices you make, the app will work out the nutritional values of everything you eat and tell you how many calories you’ve consumed. It also works in conjunction with many fitness apps to add in details of any physical activities and calories burned.

Sleep Cycle helps you get the best out of your sleep. The app analyzes how much sleep and the quality of sleep you get each night and you can also have the alarm set to wake you when you’re in your lightest sleep, leaving you feeling less groggy and more refreshed each day.

 

Article from Parkinson’s News Today.

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