Parkinson’s Treatment Tips for Constipation

Older but helpful information

Published: September 12th, 2011

By: Michael Okun

Category: Parkinson Treatment Tips, treatment

Over the years we have noticed that Parkinson’s disease patients commonly present with constipation.  We always recommend as much daily vigorous exercise as is possible, and drinking 6-8 glasses of water a day.  If that doesn’t work, we have over the last ten years handed people this formula, which has been a secret that has been refined by Janet Romrell, P.A.-C in our practice.

Constipation is an alteration in stool frequency, consistency, and/or passage of stool. The normal pattern of bowel movements can and will vary by 1 to 3 days. A stool-voiding pattern of every day or every other day is encouraged.

Causes

• Change in diet or activity
  • Lowered activity – Exercise and increased activity will assist in establishing regular bowel patterns.
  • Diet – Be sure to include fiber-rich foods:  bran, whole-grain breads – oat, rye, fruits, vegetables (leave peel on), whole-grain cereals, oatmeal, pasta, nuts, popcorn and brown rice.
• Medical Reasons –  cancer, pregnancy, hemorrhoids, neurological disorder, muscular disorder, intestinal inflammation.
• Medications –  narcotics, sedatives, antacids, antispasmodics, iron supplements
• Not drinking enough fluids – Drink at least 6 to 8, 8 ounce glasses of fluids per day. This is all inclusive (everything you drink like water, tea, coffee, juice, colas, etc.), but water is best, and we encourage you to drink primarily water. Bladder patients should reduce fluid intake after the evening meal.

Note that the daily recommended fiber intake:  20 – 30 grams

A Natural Recipe

Miller’s (unprocessed wheat) Bran*        1 cup

Applesauce                                      ½ cup

Prune Juice                                      ½ cup

Mix these ingredients together and refrigerate. Replace the mixture each week. Take 1 – 2 Tablespoons daily for one week for desired results. If needed, you may increase dose by 1 Tablespoon each week. Stool frequency and gas may increase the first few weeks but will usually adjust after one month.

*Miller’s Bran is unprocessed wheat bran. This may be purchased at most large grocery stores and is found with either the hot cereals or flours and baking goods. The most commonly found brand name is Hodgson Mill and it comes in a brown 14 oz. box. Miller’s Bran may also be purchased in bulk at health food stores.

You can also sprinkle bran on food to supplement your fiber intake.

Bowel Clean Out

The bowel clean out should be done before starting on the bowel program that is outlined for you by your physician. This should be done on a day when you will be at home all day to minimize the risk of accidentally soiling your clothes. The bowel clean out is a two-part procedure:

In the morning take 2 oz. of Milk of Magnesia and follow that with a hot drink. This could be hot coffee, hot tea or even hot broth. This helps to stimulate the bowel and enhance the effects of the Milk of Magnesia.

That evening, after dinner, give yourself a Fleet enema. This helps to make sure the rectum is empty. You should be able to rest the night without worry or discomfort.

This procedure may be repeated the next day if needed.

Medications

• Bulk producing:  Metamucil, Fibercom or Citrucel. Mix 1-2 Tablespoons in juice or water and take by mouth 1 to 2 times daily. This adds consistency or bulk to the stool and facilitates water retention in stool – must take adequate fluids by mouth to avoid causing constipation.
  • Note: some practitioners do not recommend these but other practitioners find it useful. See the quote below.
• Stool Softeners:  Colace. Softens stool by facilitating the admixture of fat and water (detergent activity). Do not use with mineral oil. Take 1 tablet by mouth 1 to 2 times daily.
• Combinations:  Pericolace. Mild stool softener and laxative combined. Take by mouth 1 to 2 times daily.
• Irritant/Stimulant:  Products containing Senna. Laxative with direct action on the intestinal mucosa and the nervous plexus of the bowel.
• Suppositories:  Glycerin, Dulcolax. Inserted rectally every other day or when needed. Stimulates the rectum and assists with evacuation.

Dr. Janis Miyasaki at the University of Toronto, recently shared her experiences in treating constipation in PD patients over many years, and I have found her approach particularly helpful (here is a blurb from her):

I learned in practice never to ask patients, “do you have a problem with constipation?” Most People With Parkinson’s don’t have a problem with constipation – they’ve been living with it for years. Now, I ask, “how often do you have a bowel movement?” Most people – even with Parkinson disease – can have a bowel movement every day. Constipation is present in more than 60% of patients and may occur even before motor symptoms like tremor and stiffness start.

Constipation is a problem because stomach emptying is also slow. As a result, your pills don’t get delivered to the part of the bowels where they can be absorbed. Your pills may be less effective. You will feel bloated and uncomfortable. Your appetite may reduce. There is evidence that constipation increases your risk for bowel cancer. In extreme cases, bowel obstruction may occur. This means that your bowels can not move because all of the stool (poop) in your gut. This is a problem because the blood supply to the gut is also blocked and your bowels can have a “stroke”. Then you will need to have surgery and possibly an ostomy bag (the gut is attached to your abdominal wall and a bag collects your stool and must be emptied at least daily).

Prevention is the key! Exercise, proper diet and enough water to help your bowels work are essential (generally eight glasses of water a day or more if you are sweating – this is more than your body needs to keep hydrated, but enough to keep your stool soft). Changing the diet to include more whole grains, avoiding white bread, pasta and rice will also help.

Your body wants to have a bowel movement in the morning. Help it by taking hot oatmeal in the morning with a hot strong cup of coffee. You can add dried figs or dates.

Avoid Metamucil or other forms of psyllium since in the slow gut, this tends to become hard and make constipation worse in Parkinson disease.

Polyethylene glycol 1350 or Miralex (available in drug stores over the counter) is also effective in Parkinson disease. The dose used in a study was 7.3 grams of macrogol dissolved in 1 cup of water twice a day.

If this doesn’t work, ask your Primary Care Physician, neurologist or movement disorders specialist for prescribed medications.

References:

Ramjit AL, Sediq L, Leibner J, Wu ss, Dai Y, Okun MS< Rodriguez RL, Malaty IA, Fernandez HH. The relationship between anosmia, constipation and orthostasis and Parkinson’s disease duration: results of a pilot study. Int J Neurosci 2010 Jan;120(1):67-70.

Zesiewicz TA, Sullivan KL, Arnulf I, Chaudhuri KR, Morgan JC, Gronseth GS, Miyasaki J, Iverson DJ, Weiner WJ. Practice parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74(11):924-31.

A Florida Blog by Michael S. Okun, M.D.

UF Center for Movement Disorders & Neurorestoration, Gainesville FL

http://movementdisorders.ufhealth.org/2011/09/12/parkinsons-treatment-tips-for-constipation/

National Veteran Resources

Veterans and Parkinson's disease

Veterans may be at an increased risk of Parkinson's disease (PD)because of their service. Evidence suggests that one cause of PD may be exposure to pesticides or herbicides. During the Vietnam War, many veterans were exposed to Agent Orange, a mix of herbicides that was used by the US military to defoliate trees and remove concealment for the enemy. There are other causes of PD as well, and most people who develop PD were never exposed to high levels of pesticides or herbicides.

Education and Clinical Centers

The Department of Veterans' Affairs (VA) established six Parkinson's Disease Research, Education, and Clinical Centers or "PADRECCs". Each PADRECC delivers state-of-the-art clinical care, conducts innovative research, and offers outreach and educational programs to all veterans currently enrolled in the VA Healthcare System. Eligible veterans include those who have been diagnosed with PD and those who have just started to notice PD-like symptoms.

PADRECCs also treat veterans diagnosed with other movement disorders, like essential tremor. PADRECCs are located in Houston, TX; Los Angeles, CA; Portland, OR; Seattle, WA; Philadelphia, PA; Richmond, VA; and San Francisco, CA.

For veterans who cannot travel to a PADRECC, the VA more than 51 Consortium Centers—VA clinics that offer specialized PD and movement-disorder specialty care. These Centers are staffed by movement disorder specialists or clinicians with vast experience and interest in the field of movement disorders. These VA Consortium Centers work collaboratively with the six PADRECCs to ensure the highest level of care for all veterans.

For more information: Call the PADRECC/Consortium Hotline at 800-949-1001, x5769 or visit their website www.parkinsons.va.go

AGENT ORANGE

Veterans exposed to Agent Orange during military service may be eligible for an Agent Orange. Registry health examination, healthcare benefits, and disability compensation. Vietnam veterans with PD or other diseases possibly associated with Agent Orange may claim benefits without having to prove that their conditions are due to Agent Orange exposure.

For more information: www.publichealth.va.gov/exposures/agentorange/ or call 800-749-8387, x3. Registry health examination, health care benefits, and disability compensation. 

Vietnam veterans with PD or other diseases possibly associated with Agent Orange may claim benefits without having to prove that their conditions are due to Agent Orange exposure.Veterans exposed to Agent Orange during military service may be eligible for an Agent Orange.

Information and services can change. Please check the Veteran's Administration website for the most accurate and up-to-date information.

http://www.apdaparkinson.org/resources-support/national-veteran-resources/

Legislators Consider a Bill to Legalize Aid-in-Dying Meds

February 16, 2017

ANNAPOLIS, Md. (AP) — In 2014, Alexa Fraser’s 90-year-old father successfully ended his life with a gun to the head after two failed suicide attempts.

Her father, whom Fraser described as a “fiercely independent person,” suffered from Parkinson’s disease, a progressive movement disorder marked by involuntary tremors and slowed movement. His condition had worsened and he feared he would be kept alive beyond his will in a nursing home so he decided to take action, Fraser said.

Since his death, Fraser has been on the forefront of Maryland’s legal aid-in-dying movement, which advocates to allow patients with a terminal diagnosis to receive a lethal prescription to painlessly end their life.

The Maryland legislature for the third year in a row is considering a joint House and Senate bill that would legalize aid-in-dying. Sponsors of previous bills have withdrawn them before a vote, citing lack of support.

“Mom has told the hospice nurse — on numerous occasions — that she just wants to go to sleep and not wake up,” Kevin Gillogly from Silver Spring, Maryland, wrote in testimony for a Thursday hearing before a pair of House committees. His mother entered hospice care in December. “As a son, I want my mom to live out her life — and death — with dignity.”

The language surrounding the issue has been contentious. Opponents resist the term legal aid-in-dying, deeming it instead as physician-assisted suicide.

“It is very important to be up front, clear and honest about what this is,” Anita Cameron, director of minority outreach for Not Dead Yet, wrote in testimony submitted for the hearing. Cameron, who also had two degenerative disabilities, wrote that the bill is referring to physician-assisted suicide.

“Couching it in pretty language and hiding the truth is disingenuous, at best, and dangerous, at worst.”

The bill would undermine the doctor-patient relationship, according to a Maryland physician.

“Instead of the doctor’s role being one of caring for those at all stages, including at the end of life, the shift would be toward patient abandonment at a time when a patient is most vulnerable,” Dr. Ellen McInerney, who practices internal medicine in Edgewater, Maryland, wrote in testimony to the committee.

Fraser, who was diagnosed with a rare form of uterine cancer in December, remains optimistic that the bills will garner enough support this year to pass. Although this legislation may eventually directly affect her own end-of-life choices, Fraser said, she continues her fight for her friends and family, not herself.

“I don’t know when I’m going to die, but what I know is there are people who right now are dying in ways they don’t want to,” Fraser said. “That is what is urgent. My situation isn’t urgent.”

Fraser testified Thursday that her son has been recently diagnosed with multiple sclerosis, a diagnosis that has not changed her support for death with dignity.

Delegate Shane Pendergrass, D-Howard, and Sen. Guy Guzzone, D-Howard, are sponsoring the bills in their respective chambers.

Pendergrass said her support for the bill stems from witnessing her grandfather’s battle with Parkinson’s. Her parents eventually no longer took her to see him in a nursing home because they didn’t want her to remember him in a debilitated state.

His brain was “absolutely alert to the very end,” Pendergrass said, but “he was locked in his body and his body was locked away from us.

“We’re all one bad death away from supporting this bill,” Pendergrass added. “Nobody wants to see their family suffer.”

The climate surrounding the issue appears to have shifted in favor of the bill since 2014, the first year it was considered.

In 2016, the Maryland State Medical Society, composed of 8,000 licensed physicians, changed its position on aid-in-dying from opposition to neutral after 65 percent of its members advocated for either support or a neutral position on the legislation.

Delegate Clarence Lam, D-Baltimore and Howard, told the University of Maryland’s Capital News Service that as a physician, he supports the bill because it enables the patients to have control over their own end-of-life decisions.

“It’s a very difficult time for patients and I’ve seen folks face some very difficult, challenging decisions,” Lam said. “For me it’s really a patient empowerment bill.”

Moreover, 69 percent of Americans say doctors should be able to end a patient’s life by painless means, according to a 2016 Gallup poll.

“I don’t see this as a partisan issue,” Lam said. “The tide of public support . has really gone in the direction in favor of this type of legislation and we feel that if folks are able to set aside their partisan biases that people will act in accordance with what’s best or their community and the other constituents (who) support this bill.”

If the bill passes, Maryland would join six other states — Oregon, Washington, Montana, Vermont, California and Colorado — that allow legal aid-in-dying. Congress is also reviewing a Washington, D.C., Council bill that would authorize the end-of-life option.

The Maryland Catholic Conference and some disability rights groups remain opposed to legal aid-in-dying legislation.

Lori Scott, a director at disability rights organization The Arc Maryland, said it’s not uncommon for someone with a disability to feel like a burden to family members, which could lead them to feel compelled to request a lethal prescription. She fears this could affect her own daughter, who is wheelchair-bound, she added.

“Disabled people are vulnerable because they like to have the assurance of people that they work with and they want to have their approval,” Scott said. “They may undertake something that they really shouldn’t be doing or don’t want to do, but want to please a provider or please a familymember.”

However, Scott said, a doctor could incorrectly give a terminal diagnosis causing “someone to end their life prematurely — an irrevocable decision,” adding that a six-month prognosis can often be “unreliable.”

Pendergrass said the bill is “tightly crafted” to protect patients from this type of abuse.

Patients eligible for the lethal medication must have two doctors diagnose them with a terminal illness with only six months or less to live, the patient must be a mentally competent adult, they must issue one oral request followed by a written request, there must be two witnesses, including one who could not directly benefit from their death, and the patient must be able to self-administer the drug.

“There are a lot of concerns about how patients may be coerced or how physicians may . lean towards greater treatment or lean towards greater end-of-life options,” Lam said. “The bill strikes a good balance between those competing concerns to make sure there are strong safeguards in place.”

Dr. Samuel Kerstein, a philosophy professor at the University of Maryland, said legal aid-in-dying legislation may be garnering more support as this generation — who have had more control over their lives than previous generations — want to be able to control their end-of-life choices as well.

Many of the arguments for legal aid-in-dying legislation — easing suffering, respecting a person’s choices and individual liberty — could also be used to support arguments for legalizing aid-in-dying for non-terminal patients as well, such as a chronically depressed individual who wanted to end his or her suffering, Kerstein added.

But Donna Edwards, Compassion and Choices Maryland campaign manager, said legal aid-in-dying legislation is far from suicide.

“The definition of suicide is a mentally incompetent person, who otherwise is fairly healthy who wants to end their life,” Edwards said. “The patients who take this, they are already terminal. They have done everything they can do to save their life. This is at the end of their lives when they decide how and the when, but the disease is killing them.”

Scott said she thinks instead of legal aid-in-dying legislation, Maryland should allocate more resources toward palliative care, which focuses on providing relief from pain, hospice care and expanding education.

“This is an option that shouldn’t even be on the table for people,” Scott said.

Fraser said palliative care and aid-in-dying aren’t mutually exclusive, adding that many people who request lethal medication don’t end up taking it, but rather use it as a source of comfort. About one-third of patients who request the prescription don’t use it, according to a 2013 report by the Oregon Public Health Division.

“This is a totally voluntary bill,” Fraser said. “If you don’t like it, don’t use it. But it’s a two-stage bill. The first stage is the legislature approves it, and then every person, with the help of their family, their doctors, their conscience and their ministers, . reaches their own conclusion.”

If the bill passes through both chambers, Gov. Larry Hogan, a Catholic, could veto it. Although he hasn’t made any public statements on the issue recently, in 2014 Hogan told a diocesan magazine, The Catholic Standard, that he would oppose the measure.

“I believe in the sanctity of human life, and I believe a physician’s role is to save lives, not terminate them,” Hogan said in that report.

A statement from the governor was unavailable at press time on Thursday afternoon.

However, Pendergrass said she doesn’t assume Hogan would veto the bill because of his religious beliefs.

“The governor has been through cancer treatment,” Pendergrass said. “I’m sure he’s suffered — not that he had a terminal diagnosis — but I suspect he came across people who did. I don’t think that they governor would want people to suffer.”

Fraser, a Unitarian Universalist minister, said there is a misconception that anyone of faith has a common view on this issue, adding that many faith leaders who have seen their congregants suffer are becoming more bold in speaking out in favor of legal aid-in-dying.

“We in public office are entrusted to keep the church and the state separate,” Pendergrass said. “We can have our personal beliefs, but we can know that our values may be different from some people and we can give them the ability to use this as one more tool.”

— Capital News Service reporter Carrie Snurr contributed to this story.

http://baltimore.cbslocal.com/2017/02/16/legislators-consider-a-bill-to-legalize-aid-in-dying-meds/

Why Standing Up Could Worsen Cognition in Parkinson's Patients with Orthostatic Hypotension

February 16, 2017

ARTICLE IN BRIEF

Parkinson's disease patients with orthostatic hypotension experienced more cognitive decline, according to a new study. The results suggest that routine blood pressure monitoring should be a part of cognitive assessment in Parkinson's disease, and point toward treatment of orthostatic hypotension as a promising approach to improving cognitive function in some patients.

Cognitive impairment is associated with orthostatic hypotension, and both are common in Parkinson's disease (PD). But does orthostatic hypotension contribute to cognitive impairment in PD? A new study published in the January 3 edition of Neurology indicates it does.

The simple but important conclusion from the study is that “when a Parkinson's disease patient with orthostatic hypotension is sitting down, he or she is going to be cognitively different than when standing up,” said the senior co-author Roy L. Freeman, MD, professor of neurology at Harvard Medical School and director of the Center for Autonomic and Peripheral Nerve Disorders at Beth Israel Deaconess Hospital in Boston.

That raises several critical issues for assessing patients, for treating them, and for advising them about remaining active in the community, he said. The results suggest that routine blood pressure monitoring should be a part of cognitive assessment in PD, Dr. Freeman added, and point toward treatment of orthostatic hypotension as a promising approach to improving cognitive function in some patients.

Little is known about the cognitive effects of orthostatic hypotension, even outside of PD, Dr. Freeman noted. Yet it is the most common autonomic disturbance in PD, affecting as many of half of patients. Cognitive impairment is similarly common in advanced disease, “but it has been difficult to disentangle the underlying disease, which itself drives cognitive impairment, from the effects of orthostatic hypotension,” Dr. Freeman said.

STUDY DESIGN

DR. ROY L. FREEMAN said the simple but important conclusion from the study is that “when a Parkinson's disease patient with orthostatic hypotension is sitting down, he or she is going to be cognitively different than when standing up.”

To address that issue, Dr. Freeman and colleagues, including first author Justin Centi, PhD, a neuropsychologist, studied 37 non-demented PD patients (18 with orthostatic hypotension and 19 without) with an average disease duration of about six years, along with 18 healthy controls. All subjects were given a battery of neuropsychological tests, first while supine, then while tilted up at 60 degrees, then again while supine, and again while upright.

Systolic blood pressure in those with orthostatic hypotension fell an average of 30 mm Hg when tilted up, compared to a decline of 5 mm Hg in PD patients without hypostatic hypotension and 2 mm Hg in controls.

PD patients as a whole performed somewhat worse on cognitive tests than controls while supine, specifically on semantic fluency, Stroop color naming, memory encoding, and delayed recall. There were no significant differences between patients with and without orthostatic hypotension on any test while in the supine position.

Upon upright tilt, the cognitive abilities of patients with and without orthostatic hypotension worsened, but the effect in those with orthostatic hypotension was much greater. On nine of the 18 individual tests performed, patients with orthostatic hypotension performed significantly worse than those without OH while tilted upright.

“What was astonishing to me was the magnitude of the deficit,” Dr. Freeman said. Even patients whose classical orthostatic hypotension symptoms were relatively mild “still had a quite profound increase in cognitive impairment, which was reversible when they returned to the supine position.”

For patients with orthostatic hypotension, “we need to be aware that the symptoms we all think of, such as presyncope, lightheadedness, and dizziness, may not encompass the entire symptom complex.” Consideration of cognitive impairment should be part of taking the full history, he said.

“We also need to think about the possibility that, in patients complaining about attention, concentration, or executive function deficits, orthostatic hypotension may be contributing to that,” even if they are not complaining about the more classical symptoms. It is also possible, though not yet tested, that treatment of orthostatic hypotension in such patients may improve their cognition.

Because cognitive testing in the clinic, which is usually performed while seated, may underestimate the degree of impairment the patient experiences while upright, it calls into question the so-called “ecological validity” of the tests — that is, how well the results predict how the patient performs on similar tasks in their daily life.

“When a patient is standing up and functioning in the world,” whether making change or crossing a street or shopping for dinner, “the degree of competency may not be predictable from the clinical results,” Dr. Freeman said. Performance is unlikely to improve, and may continue to decline the longer the patient remains upright. Over prolonged periods of standing, blood pressure may continue to fall, or at best stabilize, and “there is no reason to expect that cognition will improve when the blood pressure does not.”

EXPERTS COMMENT

DR. CHRISTOPHER HESS said assuming the results are replicated in a larger study, “clinicians need to consider the possibility that even in our patients who are not experiencing presyncope or syncopal episodes, in those patients with cognitive impairment, it may be reasonable to be more aggressive in treating their orthostatic hypotension in order to try to improve their cognitive function.”

“Although this is a small study, the results indicate it is reasonable to think that orthostatic hypotension might be a factor in cognitive impairment in a subset of PD patients, which we had not considered before,” said Christopher Hess, MD, assistant professor of neurology at the University of FloridaCollege of Medicine in Gainesville. “This could potentially represent a variable that is not being controlled for.”

Assuming the results are replicated in a larger study, he said, “clinicians need to consider the possibility that even in our patients who are not experiencing presyncope or syncopal episodes, in those patients with cognitive impairment, it may be reasonable to be more aggressive in treating their orthostatic hypotension in order to try to improve their cognitive function.”

In the same way that a complete exam includes querying about other non-motor symptoms such as depression and constipation, he added, “I think it is reasonable for all neurologists to measure a sitting and standing blood pressure in all patients, regardless of whether they are reporting symptoms.”

[Indeed, the American College of Physicians and the American Academy of Family Physicians recommend that clinicians initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. Both organizations recommend that clinicians select the treatment goals for adults aged 60 years or older based on a periodic discussion of the benefits and harms of specific blood pressure targets with the patient.]

DR. MARIO MASELLIS said the clinical implication, pending confirmation in larger studies, “is that we should be changing our practice to check for orthostatic hypotension more routinely. Unless you check for drops in blood pressure, you may miss it, because patients may not be able to tell you they are having symptoms,” and may not associate cognitive symptoms with postural changes.

“This is an important study,” commented Mario Masellis, MD, PhD, associate scientist at Sunnybrook Research Institute in Toronto, Canada, “because it is one of the first to show a definitive association between postural changes and changes in cognitive impairment in Parkinson's disease.”

The results provide a rationale for a trial targeting orthostatic hypotension in PD patients as a way to improve cognitive impairment, he said.

The clinical implication, pending confirmation in larger studies, “is that we should be changing our practice to check for orthostatic hypotension more routinely,” he said. “Unless you check for drops in blood pressure, you may miss it, because patients may not be able to tell you they are having symptoms,” and may not associate cognitive symptoms with postural changes.

In his own practice, Dr. Masellis asks caregivers to perform supine and standing blood pressure readings at home, twice a day for a week, in order to check for orthostatic hypotension that may not manifest as clearly in the clinic.

http://journals.lww.com/neurotodayonline/Fulltext/2017/02160/Why_Standing_Up_Could_Worsen_Cognition_in.7.aspx

Neurotrophic factor GDNF is an important regulator of dopamine neurons in the brain

February 16, 2017

Nerve cells. Credit: 123RF

New research results are expanding our understanding of the physiological role of the glial cell line-derived neurotrophic factor GDNF in the function of the brain's dopamine systems. In an article recently published in the Journal of Neuroscience, University of Helsinki researchers establish that GDNF is an important physiological regulator of the functioning of the brain's dopamine neurons.

Dopamine neurons have an important role in cognitive control, learning and motor control. GDNF is best known for its ability to protect dopaminergic neurons from damage, which is why it is currently in clinical trials for treatment of Parkinson's patients. Nevertheless, the significance of endogenous GDNF that is produced in our brains for the regulation of the dopamine systems is still poorly understood.

Dr Jaan-Olle Andressoo from the Institute of Biotechnology has developed new transgenic mice which have allowed researchers to gain much more reliable information on the physiological functions of GDNF. The studies were conducted in close cooperation with the research groups led by Professor Mart Saarma and Dr Petteri Piepponen, docent of pharmacology.

The new research results indicate that the GDNF produced in the brain regulates dopamine reuptake. Mice with no GDNF in their brains displayed significantly stronger reuptake of dopamine into nerve endings.

"The reuptake of dopamine is the most important factor regulating the brain's dopamine balance and signalling. In practice, this means that differences in GDNF levels might explain certain differences in people's ability to learn or focus," explains Jaakko Kopra, a researcher in Andressoo's group.

In addition, the transgenic mice had an atypically low reaction to amphetamine, which specifically targets the dopamine transporter in the brain. These observations were associated with changes in the functionality, amount and localization of the dopamine transporter in the nerve endings.

So we know that GDNF regulates the amount and localization of the dopamine transporter in the neurons, but we suspect that there may be additional mechanisms. It seems that the relationship between GDNF and dopamine transporter is surprisingly complex, which is, of course, interesting from a research viewpoint, explains Kopra.

Mice with GDNF removed from their brain in adulthood displayed very similar changes. This indicates that the underlying cause for the changes is not the impact of GDNF on brain development. The group's previously published studies on the same mouse models demonstrated that contrary to expectations, the removal of GDNF does not lead to the destruction of dopamine neurons. This means that these new results significantly expand our understanding of physiological GDNF, from a factor protecting dopamine neurons to a dynamic regulator of their function.

This knowledge is crucial for developing new treatments for not just Parkinson's disease, but also for addiction, ADHD and bipolar disorder, as all of these diseases are associated with some type of disorder in the function of the dopamine neurons, and specifically in the dopamine transporter, states Kopra.

More information: Jaakko J. Kopra et al. Dampened Amphetamine-Stimulated Behavior and Altered Dopamine Transporter Function in the Absence of Brain GDNF, The Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.1673-16.2016

Journal reference: Journal of Neuroscience

Provided by: University of Helsinki

https://medicalxpress.com/news/2017-02-neurotrophic-factor-gdnf-important-dopamine.html

Complex neurological infections require team care

February 16, 2017

Approach and implications to rating the quality of evidence and strength of recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology (unrestricted use of the figure granted by the US GRADE Network).Credit: https://academic.oup.com/cid/article/2996079/2017

A team approach is vital to the successful diagnosis and treatment of complex neurological infections related to placement of devices in the brain, or as a result of neurosurgery or head trauma. This is among the recommendations in the first comprehensive guidelines on healthcare-associated ventriculitis and meningitis, which are being released by the Infectious Diseases Society of America (IDSA) and published in the journal Clinical Infectious Diseases.

"These complicated infections affect the central nervous system and can lead to death and permanent disability if not recognized and managed appropriately," said Allan R. Tunkel, MD, PhD, lead author of the guidelines and professor of medicine and associate dean for medical education at Warren Alpert Medical School of Brown University, Providence, R.I. "While other guidelines have addressed infections in specific circumstances, these provide more comprehensive guidance to physicians of various specialties who care for these complex patients."

The guidelines provide parameters regarding when clinicians should consider the possibility of ventriculitis (inflammation of the ventricles in the brain) or meningitis (inflammation of the lining of the brain or spinal cord) in patients who have cerebrospinal fluid shunts and drains (devices placed in the brain to relieve pressure due to fluid buildup), intrathecal drug pumps (for administration of pain medicine or other drugs into the spinal canal), deep brain stimulation hardware (medical devices that provide electrostimulation in the brain to treat Parkinson's disease or other neurological symptoms) or who have undergone neurosurgery or suffered from head trauma. 

Due to the complexity of these infections, they need to be managed by a multidisciplinary team most often featuring infectious diseases (ID) specialists, neurologists, neurosurgeons and neurocritical care specialists, Dr. Tunkel said.

The guidelines help clinicians determine when to suspect ventriculitis or meningitis and start patients on appropriate antimicrobial therapy while awaiting culture results to confirm the infection and organism causing it. Vancomycin typically is the recommended antimicrobial agent of choice while clinicians await culture results, due to its success at combating the staphylococcus bacteria (a common cause of these types of infections); another antimicrobial agent is also added to treat other potential organisms. Additionally, the guidelines recommend when a device should be removed and replaced.

The guidelines also delve into various ways these infections may be prevented, such asusing prophylactic antibiotics during placement of the devices, as well as employing "practice bundles," specific steps neurosurgeons should take when placing shunts and drains.

"Specialists must work together to ensure proper management of these patients, which is critically important to improving outcome," said Dr. Tunkel. "These guidelines offer currently available evidence for treating these infections, but physicians need to use individual judgement based on how patients are responding to therapy."

More information: Allan R. Tunkel et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis*, Clinical Infectious Diseases (2017). DOI: 10.1093/cid/ciw861

Journal reference: Clinical Infectious Diseases

Provided by: Infectious Diseases Society of America

https://medicalxpress.com/news/2017-02-complex-neurological-infections-require-team.html