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|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.”|
|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.”|
|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.|
|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.1673-16.2016Journal reference: Journal of Neuroscience
Provided by: University of Helsinki
|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