Early Surgery for Drug Resistant Epilepsy May Limit Cognitive Disabilities

MedicalResearch.com Interview with:
Dr. Manjari Tripathi Professor, Epileptology, Neurology
Dr. P Sarat Chandra, Chief epilepsy Neurosurgeon
AIIMS, New Delhi

MedicalResearch.com: What is the background for this study?:

  1. Surgery for drug resistant epilepsy (DRE) is an accepted procedure for children and there have been multiple surgical series and surgical techniques published in literature. However, till date there are no randomized controlled trials (RCT) available to objectively demonstrate the safety and efficacy of surgical therapy in children with DRE. There are till date only 2 randomized trials for adult patients with drug resistant epilepsy (both for mesial temporal sclerosis only, Wiebe S et al, New Eng J Med, 2001 & Engel J et al, JAMA, 2012).
  2. Children constitute a significant proportion of patients undergoing surgical therapy for DRE (close to 50% in tertiary centers). They have unique problems associated due to uncontrolled epilepsy and some of these include epileptic encephalopathy and status epilepticus. In addition, surgery is also associated with problems like hypothermia, issues related to blood loss etc. Thus the senior author (Manjari Tripathi) and her team felt that a RCT would be very important to objectively assess the role of surgery and hence designed this study.

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More Evidence for Zika as a Causal Agent Of Guillain-Barré Syndrome

MedicalResearch.com Interview with:

Emilio Dirlikov, PhD Epidemic Intelligence Service Officer CDC 

Dr. Dirlikov

Emilio Dirlikov, PhD
Epidemic Intelligence Service Officer
CDC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In December 2015, Puerto Rico Department of Health (PRDH) reported its first confirmed locally acquired case of Zika virus disease. In February 2016, PRDH reported the first person diagnosed with Guillain-Barré syndrome (GBS) who also had evidence of Zika virus infection. At the time, scientific evidence of the potential association between Zika virus infection and GBS was lacking, and rigorous studies were needed.

Through a collaboration between PRDH, CDC, and the University of Puerto Rico (UPR), we conducted a case-control study to determine risk factors for GBS during the 2016 Zika virus epidemic. By prospectively enrolling case-patients, we shortened the time to enrollment, increasing the likelihood of detecting Zika virus nucleic acids to confirm Zika virus infection.

As a result, we found that an acute Zika virus infection confirmed by laboratory testing is a risk factor for developing Guillain-Barré syndrome. This is the first case-control study to find laboratory evidence showing this given the difficulty of confirming Zika virus infection among people diagnosed with GBS.

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Scientists Discover Why Seizures Are Harder To Control During Menstruation

MedicalResearch.com Interview with:

Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX

Dr. Samba Reddy

Dr. Samba Reddy, Ph.D., R.Ph., FAAPS, FAAAS, FAES
Professor
Neuroscience and Experimental Therapeutics
College of Medicine
Texas A&M University Health Science Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For the past two decades, D. Samba Reddy, PhD, RPh, professor of neuroscience and experimental therapeutics at the Texas A&M College of Medicine, has been searching for answers to catamenial epilepsy, a subset of chronic epilepsy that causes a dramatic increase in seizures during women’s menstrual periods. Although this condition has been documented for millennia, there is currently no effective treatment for catamenial seizures, leaving many women and their families desperate for answers.

In this report, the researchers discovers the neuro-code for treating women with menstrual period-linked epilepsy. A unique platform has been created for clinical trials for catamenial seizures with synthetic neurosteroid agents.

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Parasitic Infection With Toxoplasmosis May Be Linked To Parkinson’s & Alzheimer’s Disease

MedicalResearch.com Interview with:

Under a magnification of 900X, this hematoxylin and eosin-stained (H&E) photomicrograph of a brain tissue specimen revealed a case of neurotoxoplasmosis in a patient who had also been diagnosed with multiple myeloma. Note the Toxoplasma gondii tissue cyst, within which bradyzoites could be seen developing. CDC Image

Rima McLeod, M.D., F.A.C.P, F.I.D.S.A
Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College,
Director, Toxoplasmosis Center,
Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis,
Member Global Health Center, Affiliate CHeSS;
Attending Physician, Chicago Medicine,
The University of Chicago

MedicalResearch.com: What is the background for this study?

* One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii.
* Approximately fifteen million of these have congenital toxoplasmosis.
* The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites.
* In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process.
* Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior.
* Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases.
* Although neurobehavioral disease is associated with seropositivity, causality is unproven.
* Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality.
* Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases.
* We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design
* To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments?
* We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions.
* To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  Continue reading

Diabetes Medication Exenatide Shows Promise In Treating Parkinson’s Disease

MedicalResearch.com Interview with:
Dr Dilan Athauda MRCP
Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London

MedicalResearch.com: What is the background for this study?

Response: Exenatide is a synthetic version of a naturally occurring protein – exendin-4 – that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes.

Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival.

Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw.

As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.

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Potential Blood Biomarker Predicts Course of Huntington’s Disease

MedicalResearch.com Interview with:

Dr Edward Wild PhD MRC Clinician Scientist Huntington's Disease Centre UCL Institute of Neurology Honorary Consultant Neurologist National Hospital for Neurology & Neurosurgery, London UK

Dr. Wild

Dr Edward Wild PhD
MRC Clinician Scientist
Huntington’s Disease Centre
UCL Institute of Neurology
Honorary Consultant Neurologist
National Hospital for Neurology & Neurosurgery,
London UK

MedicalResearch.com: What is the background for this study?

Response: Having a readily accessible and sensitive biomarker, that is representative of ongoing neuropathology, could facilitate therapeutic development for Huntington’s disease. Neurofilament light (NfL) protein is one of the component that makes up the cytoskeleton of neurons. It is released when neuronal damage or death occurs and can be quantified in blood.

MedicalResearch.com: WWhat are the main findings?

Response: We carried out a retrospective cohort analysis of samples from the TRACK-HD study – a multisite longitudinal observational study of HD patients. NfL was quantified in plasma from 298 participants at baseline and follow-up. NfL was significantly higher in HD compared to healthy controls and increased with disease stage. Baseline levels of plasma NfL predicted clinical progression, including cognitive and functional decline, and the rate of global and regional brain atrophy. Premanifest individuals who converted to manifest  Huntington’s disease in the three years of the study had significantly higher levels of plasma NfL at baseline. These associations remained significant after adjustment for the combined interaction of age and CAG, currently the best predictor of age of onset of Huntington’s disease. In a separate cohort, levels of NfL in plasma and CSF were highly correlated.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: Despite decades of research, no substance in blood has shown any power to predict disease progression of Huntington’s disease. In addition, no substance has been shown to be increased as in premanifest subjects over 10 years from their predicted onset suggesting it may have potential for detecting the earliest signs of HD before overt symptoms manifest.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We hope that quantifying NfL will be incorporated into all future observational studies of  Huntington’s disease and potentially retrospectively where blood or CSF samples have been banked. We feel it should also be used in current and future clinical trials as an efficacy marker to assess whether a drug is slowing neuronal damage, at the very least as an exploratory end point. 

MedicalResearch.com: Is there anything else you would like to add?

Response: At the moment we do not have enough information for this blood test to be of clinical relevance and prognosis of a patient. A lot more research needs to be done before it could be use on an individual basis in the clinic.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: Lauren M Byrne, Filipe B Rodrigues, Kaj Blennow, Alexandra Durr, Blair R Leavitt, Raymund A C Roos, Rachael I Scahill, Sarah J Tabrizi, Henrik Zetterberg, Douglas Langbehn, Edward J Wild. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysisThe Lancet Neurology, 2017; DOI: 10.1016/S1474-4422(17)30124-2

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(17)30124-2/fulltext

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

Refined Deep Brain Stimulation Turns On ‘As Needed’ To Treat Tremors

MedicalResearch.com Interview with:

Howard Jay Chizeck ScD Professor, Electrical Engineering Adjunct Professor, Bioengineering Co-Director UW Biorobotics Laboratory Graduate Program in Neuroscience UW CoMotion Presidential Innovation Fellow Research Thrust Testbed Co-Leader

Prof. Chizeck

Howard Jay Chizeck ScD
Professor, Electrical Engineering
Adjunct Professor, Bioengineering
Co-Director UW Biorobotics Laboratory
Graduate Program in Neuroscience
UW CoMotion Presidential Innovation Fellow
Research Thrust Testbed Co-Leader

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Essential Tremor is treated using Deep Brain Stimulation (DBS) in some patients. Current clinical practice involves Deep Brain Stimulation with an “always on” stimulation. This causes extra battery drain, because stimulation is applied when not needed. Also excessive stimulation is not necessarily a good thing,

Our work is aimed at adjusting the stimulation, so that it comes on and turns off only when needed to suppress tremor symptoms.

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Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage

MedicalResearch.com Interview with:
Andrea Morotti, M.D.
Research Fellow in Neurology
Massachusetts General Hospital
Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The CT angiography (CTA) spot sign is a validated marker of Intracerebral Hemorrhage (ICH) expansion and may identify those subjects more likely to benefit from intensive blood pressure reduction.

We observed that less than 20% of ICH patients received a CTA as part of their diagnostic workup in a large, international randomized clinical trial. The performance of the spot sign in predicting ICH growth was suboptimal compared with what was reported in previous studies. Intensive blood pressure reduction did not improve functional outcome in spot sign positive patients.

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Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

MedicalResearch.com Interview with:
Rajesh Pahwa MD
Department of Neurology
University of Kansas Medical Center, Kansas City, KS,

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia.

This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017).

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Music Making Causes Rapid Neuroplastic Changes in Brain

MedicalResearch.com Interview with:

Bernhard Ross, Ph.D. Rotman Research Institute Baycrest Centre ON, Toronto

Dr. Ross

Bernhard Ross, Ph.D.
Rotman Research Institute
Baycrest Centre
ON, Toronto 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know from previous research that brain function for hearing is more strongly developed in musicians. The effect of a musician’s long-term training leads to a neuroplastic effect where their brain has more neurons involved in auditory processing. These neurons show stronger activity during listening to sound than in non-musicians and these findings strongly encouraged us to study neuroplasticity of the adult brain. We were interested in understanding why the neuroplastic effects of training and learning are so clearly expressed in professional musicians.

The study’s main finding was that actively making sound, by playing a musical instrument, changed brain responses for listening and perception. Most importantly, neuroplastic brain changes occurred very quickly, within one hour of listening and making sound. In contrast, brain changes were observed after days in previous studies that only had participants listening to sounds.

Another finding was that brain responses to hearing a sound are different when a person produces the sound themselves compared to listening to a recorded sound or a sound made by another person. This difference demonstrates that brain networks of intention, movement planning, movement execution, and expectation are involved when making a sound. We compared playing a real instrument with pressing a button for hearing a sound and found larger changes in the brain’s response to actively playing a musical instrument than pressing a button to elicit the same sound.

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Antidepressant May Enhance Drug Delivery to the Brain

MedicalResearch.com Interview with:

Ronald Cannon, Ph.D. Staff scientist at NIH’s National Institute of Environmental Health Sciences

Dr. Cannon

Ronald Cannon, Ph.D.
Staff scientist at NIH’s National Institute of Environmental Health Sciences

MedicalResearch.com: What is the background for this study?

Response: The protein pump, P-glycoprotein, is a major obstacle to the delivery of therapeutic drugs across the blood-brain barrier and into the central nervous system (CNS). During the last 10 years, our laboratory has studied the regulation of P-glycoprotein with the hope of treating CNS diseases.

MedicalResearch.com: What are the main findings?

Response: Our most recent finding shows that the antidepressant, amitriptyline, suppresses P-glycoprotein pump activity. The discovery is significant because P-glycoprotein restricts most CNS targeted drugs from entering the brain. If fully translatable to human patients, suppression of P-glycoprotein could allow higher levels of CNS therapeutic drugs to reach their intended target.

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Vagotomy May Point To Gut Origin of Parkinson’s Disease

MedicalResearch.com Interview with:

Karin Wirdefeldt, MD, PhD</strong> Associate professor Karolinska Institutet Stockholm, Sweden

Dr. Wirdefeldt

Karin Wirdefeldt, MD, PhD
Associate professor
Karolinska Institutet
Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It has been hypothesized that Parkinson’s disease may start in the gut and spread to the brain via the vagal nerve. We found that people who had a truncal vagotomy (ie, the nerve trunk fully resected) at least 5 years earlier were less likely to develop Parkinson’s disease compared to people without vagotomy or people who had a selective vagotomy (ie, only branches of the nerve resected).

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Considering Circadian Rhythms May Aide in Diagnosis of Consciousness Disorders

MedicalResearch.com Interview with:

Copyright Anna-Lisa Bexten Dr. Christine Blume PhD Post-Doctoral Researcher University of Salzburg Centre for Cognitive Neuroscience (CCNS) Laboratory for Sleep, Cognition & Consciousness Research Salzburg

Dr. Christine Blume

Dr. Christine Blume PhD
Post-Doctoral Researcher
University of Salzburg
Centre for Cognitive Neuroscience (CCNS)
Laboratory for Sleep, Cognition & Consciousness Research
Salzburg

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We are governed by rhythmic processes. Many of these processes follow a circadian pattern, that is, they have a period length of approximately 24 hours and are under tight control of a biological master clock located in the suprachiasmatic nucleus of the hypothalamus. Given the circadian variation in global states like alertness, it is not surprising that consciousness also varies rhythmically in healthy individuals, it follows the sleep-wake cycle.

From a clinical perspective, misalignment of circadian rhythms, which occurs when the sleep-wake schedule is at odds with the light-dark cycle as in the case of night shifts, can cause considerable stress, have detrimental effects on the immune system and impair cognitive abilities. Despite the knowledge that entrained circadian rhythms are important for healthy body and brain functioning, very little is known about circadian rhythms in patients diagnosed with a disorder of consciousness (DOC) following severe brain injuries. We argue that studying circadian rhythms in DOC patients may be especially interesting and important for two reasons.

First, the presence or absence of circadian rhythms as well as anomalies in them could be informative about the state of the patient as well as their potential for recovery.

Second, this could provide information about time points that best capture remaining cognitive functions thereby minimising the risk of misdiagnoses.

Beyond this, examining circadian processes may also provide targets for therapeutic interventions such as light stimulation, which has proven successful in individuals with e.g. circadian sleep disorders. Interestingly, analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3h).

We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised (CRS-R) were closely linked to the integrity of circadian variations in body temperature.

Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in two out of eight patients.

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Human Behavioral Complexity Peaks At Age 25

MedicalResearch.com Interview with:
Dr. Hector Zenil

Co-director
Information Dynamics Lab
Unit of Computational Medicine, SciLifeLab
Center for Molecular Medicine
Karolinska Institute, Stockholm, Sweden 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The generation of randomness is known to be related to cognitive abilities. It has also recently been shown that animals can recur to random behaviour to outsmart other animals or overcome certain situations. Our results that humans can best outsmart computers in generating randomness at a certain age (25). The results correspond to what it was suspected, that cognitive abilities peak at an early age before declining and that no other factor was important.

We quantified a type of mathematical randomness that is known to be the true type of randomness as opposed to e.g. ‘statistical randomness’. Something that is random is difficult to describe in a succinct way. Unlike ‘statistical randomness’, ‘algorithmic randomness’ does not only produce something that appears random but also that is very difficult to generate or produce. Conversely, something that may look random for the standard of statistical randomness may not turn out to be truly random.

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Neural Tube Defects in Infants Share Molecular Processes With Neurodegenerative Diseases

MedicalResearch.com Interview with:

Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD

Dr. Zhiyong Zhao

Zhiyong Zhao, Ph.D.
Associate Professor
Department of Obstetrics, Gynecology & Reproductive Sciences
University of Maryland School of Medicine
Baltimore, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Diabetes in early pregnancy can cause neural tube defects in fetus. The defects are a result of failure in neural tube closure, due to excess cell death. The aim of this study was to delineate molecular processes that induce cell death.

The main findings of this study are:
(1) Hyperglycemia disrupts protein folding. The misfolded proteins, including the ones that are associated with neurodegenerative diseases, form aggregates, indicating similar molecular processes in both fetal neural tube defects and adult neurodegenerative diseases.
(2) Protein aggregation leads to formation of a neurodegenerative disease-related cell death inducting mechanism.

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26 Additional Genes Linked to Intellectual Disability Identified

MedicalResearch.com Interview with:
Dr. Muhammad Ayub MBBS, MRCPsych, MSc., MD

Professor of Psychiatry Chair Division of Developmental Disabilities
Department of Psychiatry Queens
University Kingston
Kingston ON Canada

MedicalResearch.com: What is the background for this study? 

Response: Intellectual Disability affects about 1 percent of the population worldwide. Genetics play a major role in its etiology. Better understanding of the genetic causes is a necessary step in development of improved diagnosis and treatment. Recessive inheritance where the affected child inherits a defective copy of a gene from both the parents is an important genetic mechanism for prevalence of the disease in populations where within family marriages are common. These types of marital bonds are common in South Asia and Middle Eastern countries. The families where parents are related are an effective resource to study recessive forms of Intellectual Disability.

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Nasal Spray of Stem Cell Vesicles First Step Toward Treating Brain Diseases

MedicalResearch.com Interview with:

Dr. Darwin J. Prockop, M.D., Ph.D. Professor and Director Institute for Regenerative Medicine Texas A&M Health Science Center College of Medicine Temple, TX

Dr. Prockop

Dr. Darwin J. Prockop, M.D., Ph.D.
Professor and Director
Institute for Regenerative Medicine
Texas A&M Health Science Center College of Medicine
Temple, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We and many others have been trying for many years to develop therapies with adult stem cells that might rescue the brain from the injuries and disease. Recently many of found that small vesicles secreted by adult stem cells have many of the beneficial effects of the cells themselves. The paper shows that a nasal spray of the vesicles can rescue mice from the long-term effects of severe epilepsy.

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Deep Brain Stimulation Can Be Effective For Severe Tourette Syndrome

MedicalResearch.com Interview with:

Alon Y. Mogilner, M.D., Ph.D. Associate Professor of Neurosurgery and Anesthesiology Director, Center for Neuromodulation Department of Neurosurgery NYU Langone Medical Center New York, NY 10016

Alon Mogilner

Alon Y. Mogilner, M.D., Ph.D.
Associate Professor of Neurosurgery and Anesthesiology
Director, Center for Neuromodulation
Department of Neurosurgery
NYU Langone Medical Center
New York, NY 10016

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study was a review of our series of patients with Tourette’s syndrome who had failed all other treatments and who underwent deep brain stimulation (DBS), and the study demonstrated that the procedure was safe and effective in relieving their tics.

MedicalResearch.com: What should readers take away from your report?

Response:  Deep brain stimulation can be an effective treatment in patients with severe Tourette’s syndrome.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Further studies should be done to confirm which patients are most likely to benefit.

Disclosure: I have received consulting fees from Medtronic, the company who makes the implants.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Richard S. Dowd, Michael Pourfar, Alon Y. Mogilner. Deep brain stimulation for Tourette syndrome: a single-center series. Journal of Neurosurgery, 2017; 1 DOI: 10.3171/2016.10.JNS161573

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Maternal Obesity Linked To Increased Risk of Epilepsy in Offspring

MedicalResearch.com Interview with:
Neda Razaz-Vandyke, PhD, MPH
Postdoctoral Fellow
Reproductive Epidemiology Unit
Karolinska Institutet  

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:   There is a growing concern about long-term neurological effects of prenatal exposure to maternal overweight and obesity.

The etiology of epilepsy is poorly understood and in more than 60% of cases no definitive cause can be determined. We found that maternal overweight and obesity increased the risks of childhood epilepsy in a dose-response pattern.

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White Matter Trajectories Diverge In Children After Traumatic Brain Injury

MedicalResearch.com Interview with:

Emily Dennis Postdoctoral Scholar Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute USC

Emily Dennis

Emily Dennis PhD
Postdoctoral Scholar
Imaging Genetics Center
Mark and Mary Stevens Neuroimaging and Informatics Institute
USC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know that there is heterogeneity in outcome post-traumatic brain injury (TBI), but we generally think of this as a continuous variable – with most patients falling in the middle and only a few at the extremes in terms of recovery process and outcome.

Our main finding was that interhemispheric transfer time (IHTT – the time it takes for information to move from one hemisphere of the brain to the other) identified 2 subgroups of TBI patients – those with slow IHTT and those with normal IHTT. These two groups show differences in cognitive function and brain structure, with the IHTT slow group showing structural disruptions that become progressively worse while the IHTT normal group seems to be recovering from the injury.

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IQuity Developing RNA-Based Disease Activity Test for Multiple Sclerosis

MedicalResearch.com Interview with:

Dr. Chase Spurlock, Ph.D. Executive Officer at IQuity, Inc Nashville, Tennessee

Dr. Chase Spurlock

Dr. Chase Spurlock, Ph.D.
Executive Officer at IQuity, Inc
Nashville, Tennessee

IQuity is working to further develop RNA technologies that can be used to diagnose and treat Multiple Sclerosis. IQuity hopes to develop a ‘disease activity test’, which would help physicians determine when a patient is likely to relapse so that treatments can be timed for best effect.

 

MedicalResearch.com: What is the background for IQuity? What are its goals and mission?

Response: IQuity, Inc. is a biotechnology company that focuses on the research and development of innovative specialty diagnostic technology, specifically for autoimmune diseases. Our research has shown that autoimmune patients have distinct RNA expression patterns in their blood, and we have figured out how to leverage machine learning methods to analyze these RNA expression patterns and test for the presence of diseases like multiple sclerosis, IBS/IBD (Crohn’s and ulcerative colitis) and fibromyalgia. We collected patient samples from around the globe to match their RNA profiles against healthy and sick patient profiles we identified through our previous research. These tests led to the development of IQIsolate, our technology that informs the suite of tests which, when used even at the earliest onset of symptoms, can give providers information to rule in or rule out a suspected autoimmune disease with more than 90% accuracy.

Our mission is to relentlessly pursue innovation in specialized diagnostic and analytic technology, identifying complicated autoimmune and autoimmune-related diseases at the earliest signs of symptoms. We strive to enable providers to diagnose early and treat sooner in the disease progression to improve long-term outcomes, lower the overall cost of lifelong autoimmune diseases and minimize the uncertainty and fear patients experience during prolonged diagnosis periods.

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ALS: Urinary p75ECD as a Prognostic, Disease Progression, and Pharmacodynamic Biomarker

MedicalResearch.com Interview with:

Mary-Louise Rogers, PhD Senior Research Fellow, Lab Head, Motor Neurone Disease and Neurotrophic Research Laboratory, Department of Human Physiology, Centre for Neuroscience, Flinders University, School of Medicine, South Australia, Australia

Dr. Rogers

Mary-Louise Rogers, PhD
Senior Research Fellow, Lab Head,
Motor Neurone Disease and Neurotrophic Research Laboratory,
Department of Human Physiology,
Centre for Neuroscience,
Flinders University, School of Medicine,
South Australia, Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ALS is a fatal neurodegenerative disease in which motor neurons, cells that control muscle activity such as walking, talking and breathing, gradually die off, resulting in paralysis. There is no cure for ALS.

In a groundbreaking study published in the journal Neurology, and led by Mary-Louise Rogers, Ph.D., senior research fellow at Flinders University, Australia, and Michael Benatar, M.D., Ph.D, University of Miami, Miller School of Medicine,  have identified concentrations of p75ECD, the extracellular domain on the common neurotrophin receptor p75, as the first biological fluid-based biomarker for ALS progression. .

Neurotrophin receptor p75 is a growth factor receptor for neurotrophins whom promote the survival of nerve cells. Under normal circumstances, it is highly expressed on motor neurons during development but decreases after birth. Following nerve injury, however, the expression of p75 is increased and the extracellular domain of p75 is detectable in urine. Dr Rogers and her Doctoral student Stephanie Shepheard hypothesized and then showed, that p75ECD is excreted into the urine of SOD1 mice, the most commonly used animal model of ALS. These findings empowered further investigation of p75ECD, showing raised levels in the urine of patients with ALS and that it might have potential as an ALS biomarker.

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Reward Circuit in Brain Localized To Central Amygdala

MedicalResearch.com Interview with:
Joshua Kim, researcher
RIKEN-MIT Center for Neural Circuit Genetics at The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Howard Hughes Medical Institute, Massachusetts Institute of Technology
Cambridge, MA 02139

MedicalResearch.com: What is the background for this study?

Response: We previously identified to populations of neurons in a structure known as the basolateral amygdala, one that is capable of mediated fear-related behaviors and the other reward-related behaviors. Both of these basolateral amygdala populations send projections to a structure known as the central amygdala.

For this study, we wanted to examine the function of 7 different populations of central amygdala neurons in regard to fear-related and reward-related function and how each of these 7 populations are connected to the 2 basolateral amygdala populations.

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Multiple Sclerosis Patients Show Cognitive Benefit From Remotely Supervised Transcranial Direct Current Stimulation

MedicalResearch.com Interview with:

Leigh E. Charvet, PhD Associate Professor, Department of Neurology Department of Neurology New York University Langone Medical Center New York, NY

Dr. Charvet

Leigh E. Charvet, PhD
Associate Professor, Department of Neurology
Department of Neurology
New York University Langone Medical Center
New York, NY

MedicalResearch.com: What is the background for transcranial direct current stimulation? What are the main findings of this study in multiple sclerosis patients?

Response: The application of tDCS is a relatively recent therapeutic development that utilizes low amplitude direct currents to induce changes in cortical excitability. When paired with a rehabilitation activity, it may improve learning rates and outcomes.

Multiple repeated sessions are needed for both tDCS and cognitive training sessions to see a benefit. Because it is not feasible to have participants come to clinic daily for treatments, we developed a method to deliver tDCS paired with cognitive training (using computer-based training games) to patients at home. Our protocol uses a telemedicine platform with videoconferencing to assist study participants with all the procedures and to ensure safety and consistency across treatment sessions.

When testing our methods, we enrolled 25 participants with multiple sclerosis (MS) completed 10 sessions of tDCS (2.0 mA x 20 minutes, dorsolateral prefrontal cortex, left anodal) using the remotely-supervised telerehabilitation protocol. This group was compared to n=20 MS participants who completed 10 sessions of cognitive training only (also through remote supervision).

We administered cognitive testing measures at baseline and study end. We found that both the tDCS and cognitive training only group had similar and slight improvements on composites of standard neuropsychological measures and basic attention. However, the tDCS group had a significantly greater gain on computer-based measures of complex attention and on a measure of intra-individual variability in response times.

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Subtle Differences in Brain Volume Detected On MRI In ADHD

MedicalResearch.com Interview with:
M. (Martine) Hoogman PhD.

Postdoc and PI of ENIGMA-ADHD
Radboud universitair medisch centrum
Department of Human Genetics
Nijmegen, The Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are many neuro-imaging studies aimed at investigating structural brain changes related to ADHD, but the results are often inconclusive.

There are two main reasons for this:

1) the small sample size of the studies and
2) the heterogeneous methods used.

We tried to address these issues by forming an international collaboration to provide a sample size sufficient to detect even small effects in volume differences. And in addition, we analyzed all the raw scans again using homogenized methods. There are data of more than 1700 patients (aged 4-63 years of age) and more than 1500 healthy controls in our dataset, coming from 23 sites around the world. We studied the possible volume differences between cases and controls of 7 subcortical regions and intracranial volume by performing mega- and meta-analysis.

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mGlu2 receptor Agonist ADX71149 Plus Levetiracetam May Reduce Seizures With Fewer Side Effects

MedicalResearch.com Interview with:

Robert Lutjens, PhD Head of Discovery at Addex Therapeutics Geneva, Switzerland

Dr. Lutjens

Robert Lutjens, PhD
Head of Discovery at Addex Therapeutics
Geneva, Switzerland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Metabotropic glutamate receptors represent an attractive therapeutic target for various neurologic conditions. In particular, the metabotropic glutamate receptor subtype 2 (mGlu2) can affect excitatory synaptic transmission by decreasing glutamate release. As excess gluatamate is observed in epilepsy, targeting mGlu2 could lead to new avenues of therapy. Positive allosteric modulators (PAMs) of mGlu2 could be valuable candidate drugs as they do not directly activate receptors. Therefore, they may avoid tachyphylaxis and side effects emerging from direct receptor agonism. 

The publication summarizes the effects obtained when the mGlu2 receptor is activated using an agonist or PAM, such as ADX71149, in the 6Hz psychomotor seizure test, considered to be the most relevant model of pharmacoresistant limbic seizures. The data show that while seizures are reduced when mGlu2-acting compounds are administered alone, their combination with the antiseizure drug levetiracetam (LEV) result in a potent reduction of doses required to produce full efficacy, which is important because higher doses of LEV are associated with dose-limiting side effects, such as aggression, nervousness/anxiety, somnolence and fatigue. In this study, a fixed dose of ADX71149 was seen to increase the potency of LEV, leading to an approximate 35-fold increase in its potency. Conversely, using a fixed dose of LEV with varying doses of ADX71149 resulted in an approximate 14-fold increase in ADX71149 potency.

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More Children Means Increasingly Less Sleep For Mothers

MedicalResearch.com Interview with:

Kelly L. Sullivan, PhD Assistant Professor Department of Epidemiology Jiann-Ping Hsu College of Public Health Georgia Southern University Statesboro, Georgia

Dr. Sullivan

Kelly L. Sullivan, PhD
Assistant Professor
Department of Epidemiology
Jiann-Ping Hsu College of Public Health
Georgia Southern University
Statesboro, Georgia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The original aim of this study was to determine which factors were associated with getting sufficient sleep in men and women. In this analysis, we considered many possible influences including BMI, age, race, education, marital status, exercise, employment status, and income in addition to having children in the household. The aim was to determine which factors were most strongly associated with insufficient sleep in men and women specifically in order to inform efforts to best address their sleep challenges.

In this study, we found that younger women with insufficient sleep time were more likely to have children in the household compared with women who reported sufficient sleep. Each child in the household was associated with a nearly 50% increase in a woman’s odds of insufficient sleep.

This finding held after controlling for the potential effects of age, exercise, employment status and marital status. Children in the household were also associated with the frequency of feeling unrested among younger women, but not among younger men. Women with children reported feeling tired about 25% more frequently compared to women without children in the household.

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Human Genetics Contributes To Zika-Induced Brain Damage

MedicalResearch.com Interview with:

Ping Wu, MD, PhD John S. Dunn Distinguished Chair in Neurological Recovery Professor, Department of Neuroscience & Cell Biology University of Texas Medical Branch Galveston, TX 77555-0620

Dr. Ping Wu

Ping Wu, MD, PhD
John S. Dunn Distinguished Chair in Neurological Recovery
Professor, Department of Neuroscience & Cell Biology
University of Texas Medical Branch
Galveston, TX 77555-0620

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika viral infection poses a major global public health threat, evidenced by recent outbreaks in America with many cases of microcephaly in newborns and other neurological impairments. A critical knowledge gap in our understanding is the role of host determinants of Zika-mediated fetal malformation. For example, not all infants born to Zika-infected women develop microcephaly, and there is a wide range of Zika-induced brain damage. To begin to fill the gap, we infected brain stem cells that were derived from three human donors, and found that only two of them exhibited severer deficits in nerve cell production along with aberrant alterations in gene expression.

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Long Term Fampridine (AMPYRA) Improves Gait Function in Multiple Sclerosis

MedicalResearch.com Interview with:

Linard Filli, PhD Gait Research Lab Department of Neurology University Hospital Zurich Zürich

Dr. Linard Filli

Linard Filli, PhD
Gait Research Lab
Department of Neurology
University Hospital Zurich
Zürich

MedicalResearch.com: What is the background for this study?

Response: Gait dysfunction is common in patients with multiple sclerosis (MS) and is perceived as the most restricting of symptoms. Fampridine (4-aminopyridine, dalfampridine), a blocker of voltage-gated potassium channels, is currently the only approved medication for the symptomatic treatment of walking disorders in patients in both the early and late phases of  multiple sclerosis.

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Genetically Predisposed Patients May Develop ALS At Earlier Age

MedicalResearch.com Interview with:
Prof. Dr. Christine Van Broeckhoven PhD DSc
Professor in Molecular Biology and GeneticsUniversity of Antwerp
Science Director, VIB Center for Molecular Neurology
Research Director, Laboratory for Neurogenetics, Institute Born-Bunge
Senior Group Leader, Neurodegenerative Brain Diseases
University of Antwerp and
Dr. Sara Van Mossevelde, MD
Center for Molecular Neurology, VIB
Institute Born-Bunge, University of Antwerp
Department of Neurology and Memory Clinic
Hospital Network Antwerp Middelheim and Hoge Beuken
Antwerp, Belgium

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Patients with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) and a C9orf72 repeat expansion present with highly variable onset ages of disease. In the Belgian patient cohort the onset ages ranged from 29 to 82 years of age. This high variability suggested the influence of modifying factors on disease expression. As in other repeat expansion diseases, repeat length is the prime candidate as genetic modifier. In a molecular study (Gijselinck et al., Molecular psychiatry 2016), we were able to provide evidence for an inverse correlation of repeat length with onset age in affected parent – affected children in a C0orf72 families. Also, the degree of methylation of the C9orf72 repeat correlated with repeat size.

In this clinical study of affected parent – affected children pairs we provided additional evidence for the occurrence of disease anticipation in C9orf72 pedigrees by analyzing age at onset, disease duration and age at death in successive generations. Within 36 C9orf72 pedigrees with available age data of patients in two to four generations, we observed a significant decrease in age at onset across successive generation while no generational effect was seen on disease burden, disease duration or age at death.

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Cerebral Microinfarcts Associated With Cardiac Biomarkers and Heart Disease

 

Christopher Chen, FRCP Department of Pharmacology Yong Loo Lin School of Medicine Memory Aging and Cognition Center National University Health System Singapore Saima Hilal, PhD Department of Pharmacology, National University of Singapore Department of Radiology, Epidemiology and Nuclear Medicine Erasmus Medical Center, Rotterdam, the Netherlands

 

 

MedicalResearch.com Interview with:
Christopher Chen, FRCP

Department of Pharmacology
Yong Loo Lin School of Medicine
Memory Aging and Cognition Center
National University Health System
Singapore
Saima Hilal, PhD
Department of Pharmacology, National University of Singapore
Department of Radiology, Epidemiology and Nuclear Medicine
Erasmus Medical Center, Rotterdam, the Netherlands

MedicalResearch.com: What is the background for this study?

Response: Cerebral microinfarcts (CMIs) are defined as small (usually <1 mm) regions of ischemic change found in the brain which are not readily visible on gross examination or on standard 1.5-T magnetic resonance imaging (MRI). On microscopy they appear as foci of neuronal loss, gliosis, pallor, or cysts.

Previous post mortem studies have shown that the presence of CMIs is relatively common in elderly individuals without dementia (24%) but more common in patients diagnosed with Alzheimer disease (43%) or vascular dementia (62%).

Whilst a single CMI is likely to be “silent” as the region of brain affected is probably too small to produce symptoms or neurologic deficits, however, as a large number of CMIs exist in many individuals, especially in the cerebral cortex and watershed areas, the overall effect has clinical importance – as shown by neuropathologic studies which demonstrate an important role of CMIs in cognitive dysfunction and dementia. However in vivo studies have been hampered by the inability to detect CMIs reliably on neuroimaging, leading to CMIs being termed “invisible” during life.

The advent of high spatial-definition 7-T MRI enabled the identification of cortical  Cerebral microinfarcts in-vivo and importantly a study that directly compared 7-T and 3-T MRIs in the same patients reported that 3-T MRI detected about 1/3 of the lesions found on 7-T MRIs, suggesting that 3-T MRIs, which are more accessible than 7-T, may be able to detect larger cortical CMIs with a lower limit of approximately 1 mm in diameter.

Our group has made major contributions recently on the clinical associations of 3T MRI detected cortical CMIs in patients from memory clinics as well as in community based subjects. Associations were found with age, vascular risk factors, other MRI markers of cerebrovascular disease as well as cognition. However, the causes of CMIs remain unclear and may be heterogeneous with microembolism, microthrombosis, and foci of inflammation as possible causative factors.

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Brain–Computer Interface Allows Communication With Locked-In Patients

MedicalResearch.com Interview with:

Dr. Ujwal Chaudhary, PhD Institute of Medical Psychology and Behavioral Neurobiology University of Tübingen Tübingen, Germany

Dr. Ujwal Chaudhary

Dr. Ujwal Chaudhary, PhD
Institute of Medical Psychology and Behavioral Neurobiology
University of Tübingen
Tübingen, Germany

MedicalResearch.com: What is the background for this study?

Response: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder which causes an Individual to be in Locked-in state (LIS), i.e. the patients have control of their vertical eye movement and blinking, and ultimately in Completely Locked-in state (CLIS), i.e, no control over their eye muscle. There are several assistive and augmentative (AAC) technology along with EEG based BCI which can be used be by the patients in LIS for communication but once they are in CLIS they do not have any means of communication.  Hence, there was a need to find an alternative learning paradigm and probably another neuroimaging technique to design a more effective BCI to help ALS patient in CLIS with communication.

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Multiple Treatment Options Now Available for Multiple Sclerosis

MedicalResearch.com Interview with:

Tomas Kalincik, MD, PhD, PGCertBiostat Neurologist and Senior Research Fellow Melbourne Brain Centre | Department of Medicine | University of Melbourne Department of Neurology | Royal Melbourne Hospital Melbourne | Victoria | Australia

Dr. Tomas Kalincik

Tomas Kalincik, MD, PhD, PGCertBiostat
Neurologist and Senior Research Fellow
Melbourne Brain Centre | Department of Medicine | University of Melbourne
Department of Neurology | Royal Melbourne Hospital
Melbourne | Victoria | Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple sclerosis is a disease predominantly of young adults, with the peak of incidence in the 3rd and 4th decades. It is the most common cause of neurological disability in young adults. Only in Australia, 23,000 people are living with MS, with MS representing an annual cost of almost 1 billion $AU to the Australian society. It is a disease that presents with broad range of neurological symptoms and signs, which are typically temporary (these are called relapses) that with time can lead to permanent neurological disability. While there is currently no cure for MS, with appropriate therapy, its symptoms can be controlled and the disability progression slowed down.

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Key Gene Linked To Brain Plasticity and Learning Identified

MedicalResearch.com Interview with:

Keerthi Krishnan PhD</strong> Cold Spring Harbor Laboratory Cold Spring Harbor, New York 11724,

Dr. Keerthi Krishnan

Keerthi Krishnan PhD
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York 11724

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Rett Syndrome is diagnosed as a neurodevelopmental disorder in girls, caused mainly by mutations in the gene MECP2. Many previous studies, including mine, have shown that mutations in MECP2 result in improper communication between nerve cells in the brain during sensitive periods of development. However, it was unclear if the same mechanisms were responsible for cognitive and behavioral problems found in adulthood.

In this paper, we have utilized a natural, learned response called pup retrieval behavior to study adult neural plasticity in a female mouse model of Rett Syndrome. With some learning, adult female mice will gather scattered pups to the nest, in response to distress calls from the pups. We found that the Rett Syndrome model mice with reduced MECP2 protein do not gather pups efficiently. This is due to the abnormal formation of structures called perineuronal nets on a specific type of neurons (called parvalbumin+ GABAergic neurons) that block plasticity and prevent learning of the appropriate response. Furthermore, the same neural and molecular mechanisms found earlier in development were also found to mediate learning in adulthood.

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Majority of Neurologists Report Symptoms of Burnout

MedicalResearch.com Interview with:

Neil A. Busis, M.D. University of Pittsburgh Physicians Department of Neurology Chief of Neurology, UPMC Shadyside Director of Community Neurology

Dr. Neil A. Busis

Neil A. Busis, M.D.
University of Pittsburgh Physicians
Department of Neurology
Chief of Neurology, UPMC Shadyside
Director of Community Neurology

MedicalResearch.com: What is the background for this study?

Response: Previous studies showed that neurologists have both one of the highest rates of burnout and the lowest rates of satisfaction with work-life balance, compared to other physicians.

The mission of the American Academy of Neurology (AAN) is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction. This is why AAN President Dr. Terrence Cascino initiated this research, to better define the issue. Our findings can guide current and future programs to prevent and mitigate neurologist burnout, promote neurologist career satisfaction and well-being, and direct efforts to advocate on behalf of neurologists and their patients.

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Reduced Stem Cells Link Congenital Heart Disease To Impaired Brain Growth

MedicalResearch.com Interview with:

Childrens National Research Team

Children’s National Research Team

Paul D. Morton, Ph.D.
Research PostDoc and lead study author of “Abnormal Neurogenesis and Cortical Growth in Congenital Heart Disease.”
Children’s National Health System Washington, DC

Nobuyuki Ishibashi, M.D.
Director of the Cardiac Surgery Research Laboratory at Children’s National Health System and co-senior study author.

Vittorio Gallo, Ph.D.
Director of the Center for Neuroscience Research at Children’s National Health System and co-senior study author.

 

 

Richard A. Jonas, M.D.
Chief of the Division of Cardiac Surgery at Children’s National Health System and co-senior study author.

MedicalResearch.com: What is the background for this study?

Response: Congenital heart disease (CHD) is the leading birth defect in the United States and often results in an array of long-term neurological deficits including motor, cognitive and behavioral abnormalities. It has become increasingly clear that children with CHD often have underdeveloped brains. In many cases of complex CHD, blood flow to the brain is both reduced and less oxygenated, which has been associated with developmental abnormalities and delay. The cellular mechanisms underlying the impact of CHD on brain development remain largely unknown. We developed a preclinical chronic hypoxia model to define these mechanisms.

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Our Personality is Shaped By Wrinkles and Folds of Our Brain

MedicalResearch.com Interview with:

Dr. Roberta Riccelli Magna Graecia University Catanzaro, Italy

Dr. Roberta Riccelli

Dr. Roberta Riccelli
Magna Graecia University
Catanzaro, Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years, there has been a growing interest in personality neuroscience, an emergent field of research exploring how the extraordinary variety of human behaviors arise from different patterns of brain function and structure. According to psychologists, the extraordinary variety of human personality can be broken down into the so-called ‘Big Five’ personality traits, namely neuroticism (how moody a person is), extraversion (how enthusiastic a person is), openness (how open-minded a person is), agreeableness (a measure of altruism), and conscientiousness (a measure of self-control).

However, the relationships between personality profile and brain shape remains still poorly characterized and understood.

The findings of our study highlighted that the personality type characterizing each person is connected to the brain shape of several regions implicated in emotional behaviors and control. We found that neuroticism, a personality trait underlying mental illnesses such as anxiety disorders, was linked to a thicker cortex (the brain’s outer layer of neural tissue) and a smaller area and folding in some brain regions. Conversely, openness, a trait reflecting curiosity and creativity, was associated to thinner cortex and greater area and folding in the brain. The other personality traits were linked to other differences in brain structure, such as agreeableness being correlated with a thinner prefrontal cortex (which is linked to empathy and other social skills). Overall, all the traits characterizing this model of personality are related to some features (e.g. thickness, area and folding) of brain regions implicated in attention, salience detection of stimuli and emotion processing. This could reflect the fact that many personality traits are linked to high-level socio-cognitive skills as well as the ability to modulate ‘core’ affective responses.

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Amygdala Region in Brain Not So Different in Men and Women

MedicalResearch.com Interview with:

Lise Eliot PhD Associate Professor of Neuroscience Chicago Medical School Rosalind Franklin University North Chicago, IL 60064

Dr. Lise Eliot

Lise Eliot PhD
Associate Professor of Neuroscience
Chicago Medical School
Rosalind Franklin University
North Chicago, IL 60064

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Studies in rats indicate that the amygdala, which is important for many social behaviors including aggression and rough-and-tumble play, is larger in male animals.  Early MRI studies also reported that the human amygdala is larger in men, even after correcting for males’ larger overall brain size.  Because so many MRI studies are now imaging amygdala volume in matched groups of healthy males and females, we realized that there is a lot of published data that could settle whether the human amygdala is indeed proportionally larger in men.  Another rationale for the study is that many psychiatric disorders that involve the amygdala (e.g., depression, anxiety, substance abuse) differ in prevalence between men and women.

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Standardized EEG Reporting Helps Predict Risk of Seizures

MedicalResearch.com Interview with:

Andres Rodriguez Ruiz, MD</strong> Clinical Neurophysiology and Neurology Emory School of Medicine

Dr. Andres Rodriguez Ruiz

Andres Rodriguez Ruiz, MD
Clinical Neurophysiology and Neurology
Emory School of Medicine

MedicalResearch.com: What is the background for this study?

Response: The Critical Care EEG monitoring research consortium (CCEMRC) was established with the goal of promoting collaboration and research among healthcare institutions highly involved in continuous EEG monitoring of critically ill patients. This group together with the American Clinical Neurophysiology Society (ACNS) established the standardized critical care EEG terminology that allowed uniform reporting of EEG findings in critically ill patients. As part of this effort, a database was developed for collection and clinical reporting of such EEG findings and was adopted for daily clinical use by Yale University, Emory University and Brigham and Women’s Hospital.

Prior retrospective reports have acknowledged an association between periodic discharges and seizures. However, many of these reports were small series and did not include specific characteristics of these patterns. Our goal was to ascertain whether features of periodic and rhythmic patterns such as location (generalized vs. lateralized), frequency and prevalence influenced seizure risk in a large cohort of critically ill adults.

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CSF Biomarker May Signal Progression of Clinically Isolated Syndrome to MS

MedicalResearch.com Interview with:

Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, PB 2040 Rotterdam

Prof Rogier Q Hintzen

Prof Rogier Q Hintzen
Neurologist/immunologist
Head MS Centre ErasMS
Dept of Neurology
Erasmus MC, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.)
As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient.
Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment.
We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls.

In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course.

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Stuttering Linked To Decreased Blood Flow to Broca’s Area in Brain

MedicalResearch.com Interview with:

Jay Desai, M.D. Neurologist, Children’s Hospital Los Angeles Assistant Professor, Keck School of Medicine of USC

Dr. Jay Desai

Jay Desai, M.D.
Neurologist, Children’s Hospital Los Angeles
Assistant Professor, Keck School of Medicine of USC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We obtained measures of blood flow at rest from all regions of brain using an MRI technique called pulsed arterial spin labeling in 26 participants (children and adults) with stuttering. We compared these blood flow measures with those from 36 fluent controls. We found decreased blood flow in Broca’s region in participants with stuttering when compared to the fluent controls. The amount of blood flow correlated inversely with the severity of stuttering and these findings extended into other portions of the language loop. We also detected alterations in blood flow in other brain regions including superior frontal gyrus, cerebellar nuclei and parietal cortex.

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Neuroanatomy Accounts for Age-Related Changes in Risk Preferences.

MedicalResearch.com Interview with:
Ifat Levy, PhD

Associate Professor
Comparative Med and Neuroscience
Yale School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The proportion of older adults in the population is rapidly rising. These older adults need to make many important decisions, including medical and financial ones, and therefore understanding age-related changes in decision making is of high importance. Prior research has shown that older adults tend to be more risk averse than their younger counterparts when making choices between sure gains and lotteries. For example, asked to choose between receiving $5 for sure and playing a lottery with 50% of gaining $12 (but also 50% of gaining nothing), older adults are more likely than young adults to prefer the safe $5. We were interested in understanding the neurobiological mechanisms that are involved in these age-related shifts in preferences.

An earlier study that we have conducted in young adults provided a clue. In that study, we measured the risk preference of each participant (based on a series of choices they made between safe and risky options), and also used MRI to obtain a 3D image of their brain. Comparing the behavioral and anatomical measures, we found an association between individual risk preferences and the gray-matter volume of a particular brain area, known as “right posterior parietal cortex” (rPPC), which is located at the back of the right side of the brain. Participants with more gray matter in that brain area were, on average, more tolerant of risk (or less risk averse).

This suggested a very interesting possibility – that perhaps the increase in risk aversion observed in older adults is linked to the thinning of gray matter which is also observed in elders. In the current study we set out to test this hypothesis, by measuring risk preference and gray matter density in a group of 52 participants between the ages of 18 and 88. We found that, as expected, older participants were more risk averse than younger ones, and also had less gray matter in their rPPC. We also replicated our previous finding – that less gray matter was associated with higher risk aversion. The critical finding, however, was that the gray matter volume was a better predictor of increased risk aversion than age itself.  Essentially, if both age and the gray matter volume of rPPC were used in the same statistical model, rPPC volume predicted risk preferences, while age did not. Moreover, the predictive power was specific to the rPPC – when we added the total gray matter volume to the model, it did not show such predictive power.

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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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Multiple Sclerosis: Brain Atrophy Linked to Leaked Hemoglobin

MedicalResearch.com Interview with:

Charles Bangham PhD ScD Division of Infectious Diseases, Department of Medicine Imperial College London London, UK

Dr. Charles Bangham

Charles Bangham PhD ScD
Division of Infectious Diseases, Department of Medicine
Imperial College London
London, UK

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) is a neurological disease of the brain and spinal cord, often beginning in the 20s and 30s which can cause both attacks (relapses) and disability over time. Most people with the condition have intermittent episodes of illness at first, but about two-thirds go on to develop a progressive form, known as secondary progressive MS. In this form, there is a gradual loss of nerve cells in the brain, resulting in shrinkage of the brain and progressive disability.

Neither the initiating cause of  Multiple sclerosis nor the reasons for this brain shrinkage are known, and existing treatments for the early phase of the condition are unsatisfactory.

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Non-Invasive Interface Allows Subjects To Control Objects With Just Thoughts

MedicalResearch.com Interview with:

Bin He, Ph.D. Director, Institute for Engineering in Medicine Director, Center for Neuroengineering Distinguished McKnight University Professor of Biomedical Engineering Medtronic-Bakken Endowed Chair for Engineering in Medicine University of Minnesota, Minneapolis, MN 55455

Dr. Bin He

Bin He, Ph.D.
Director, Institute for Engineering in Medicine
Director, Center for Neuroengineering
Distinguished McKnight University Professor of Biomedical Engineering
Medtronic-Bakken Endowed Chair for Engineering in Medicine
University of Minnesota, Minneapolis, MN 55455

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This work is aimed at developing a noninvasive brains-computer interface to allow disabled patients to control their environment by just thinking about it.

We found 8 human subjects were able to accomplish 3D reach and grasp tasks without using any muscle activities but just thinking about it.

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Nasal Swab Can Test for Creutzfeldt–Jakob Disease

MedicalResearch.com Interview with:
Zanusso Gianluigi M.D.Ph.D.

Department of Neurosciences, Biomedicine and Movement Sciences
University of Verona
Verona, Italy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: To determine RT-QuIC assay sensitivity and specificity in cerebrospinal fluid and olfactory mucosa in a large group of patients with a clinical diagnosis of probable, possible or suspect Creutzfeldt–Jakob disease (CJD) and controls.

In these patients, RT-QuIC testing of CSF and olfactory mucosa provided a specificity and sensitivity of 100%.

A softer swab for olfactory mucosa sampling provided the same sensitivity as using a brush .

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Diabetes Drug May Slow Progression of Parkinson’s Disease

MedicalResearch.com Interview with:

Patrik Brundin, M.D., Ph.D. Director, Center for Neurodegenerative Science Van Andel Research Institute

Dr. Patrik Brundin

Patrik Brundin, M.D., Ph.D.
Director, Center for Neurodegenerative Science
Van Andel Research Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The investigational drug at the heart of our study, MSDC-0160, has been in development to treat type 2 diabetes by improving cellular metabolism.

In Parkinson’s, reductions in cellular metabolism slow down vital housekeeping processes that clear out toxic proteins that otherwise accumulate with age. If these proteins aren’t removed, they clump together, leading to the damage and cell death that causes Parkinson’s hallmark symptoms, such as rigidity and tremor. MSDC-0160 helps keep these housekeeping processes working, ultimately protecting the brain.

We demonstrated that MSDC-0160 has strong, reproducible, positive effects across multiple models of Parkinson’s disease—it rescued dopamine-producing cells, improved behavioral deficits in mouse models and reversed inflammation. Overall, we believe it is a strong candidate for repurposing as a potential treatment that actually may slow the disease’s progression, rather than only mitigating symptoms.

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Neuroactive Steroids Evoke Inhibition Through Protein Kinase C Mechanism

MedicalResearch.com Interview with:

Dr. Paul Davies PhD Tufts University School of Medicine Department of Neuroscience Boston, MA 02111

Dr. Paul Davies

Dr. Paul Davies PhD
Tufts University School of Medicine
Department of Neuroscience
Boston, MA 02111

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Inhibition in the brain regulates neuronal action potential generation, too little inhibition can directly cause conditions such as epileptic seizures, neurodevelopment disorders, and neurodegenerative disorders. The main type of inhibition in the mammalian brain occurs when the neurotransmitter γ-aminobutyric acid (GABA) binds to the GABA type A receptors (GABAARs), a ligand-gated ion channel. Once bound with GABA, the receptor changes shape to open the ion channel allowing negative charged chloride ions to flow through into the cell and inhibiting excitation steaming from positive charged ions flowing through opposing excitatory ion channels. GABAARs mediate both synaptic (phasic) and extrasynaptic (tonic) inhibitory neurotransmission in the CNS and are the sites of action of benzodiazepines, barbiturates, general anesthetics and neuro-active steroids. We have been focused on the extrasynaptic GABAARs that mediate tonic inhibition. In the dentate gyrus of the hippocampus, neocortex, striatum and the thalamus tonic inhibition is largely dependent on GABAARs composed of α4, β2/3, and δ subunits. Neuro-active steroids play a central role in regulating behavior via their ability to allosterically enhance GABAARs, particularly extrasynaptic α4-containing GABAARs. Allosteric enhancement means that neuro-active steroids bind to GABAARs and cause a further change in the structure of the ion channel allowing it to remain open for longer.

For the last few decades, allosteric enhancement of GABAARs by neuro-active steroids has been the prevailing explanation for how the steroids increase inhibition in the brain. However, recently we described a new mechanism where the neuro-active steroid, THDOC, increased the association of protein kinase C (PKC) with extrasynaptic α4β3 subunit-containing GABAARs. The increase in PKC-mediated phosphorylation of α4 and β3 subunits leads to an increase in membrane insertion from intracellular stores, an increase in GABAAR stability in the membrane, and a prolonged increase of tonic inhibition, even after when the neuro-active steroids have been removed.
For this present study we asked whether other neuro-active steroids demonstrated the same metabotropic activity. We tested another endogenous neuro-active steroid, allopregnanolone (ALLO), and the synthetic neuro-active steroid, ganaxolone. In collaboration with SAGE Therapeutics, we also tested another synthetic neuro-active steroid, SGE-516.

We found that all the neuro-active steroids tested were able to allosterically potentiate both synaptic and, to a lesser degree, extrasynaptic GABAARs. Short 15-minute exposures to neuro-active steroids resulted in significantly increase in phosphorylation of β3 subunits, and long lasting enhancement of tonic current. These increases were metabotropic in nature, being dependent upon PKC mediated phosphorylation. Following this short 15-minute exposure we saw a change in synaptic currents only with SGE-516 suggesting a selectivity of this metabotropic pathway to extrasynaptic GABAARs. Although ganaxolone was an effective allosteric modulator, it did not produce a metabotropic enhancement of tonic current suggesting that not all neuroactive steroids work through this pathway.

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Vestibular or Inner Ear System Weakens After Age 40

MedicalResearch.com Interview with:

Daniel M. Merfeld, Ph.D. Professor of Otolaryngology Harvard Medical School Massachusetts Eye and Ear Director, Jenks Vestibular Physiology Laboratory Senior Scientist

Dr. Daniel M. Merfeld

Daniel M. Merfeld, Ph.D.
Professor of Otolaryngology
Harvard Medical School
Massachusetts Eye and Ear
Director, Jenks Vestibular Physiology Laboratory
Senior Scientist

MedicalResearch.com: What is the background for this study?

Response: Nearly half of the population will see a clinician at some point in their lives with symptoms related to the vestibular system (e.g., dizziness, vertigo, imbalance and blurred vision). The vestibular system, made up of tiny fluid-filled membranes in the inner ear, is responsible for receiving information about motion, balance and spatial orientation. With the goal of determining whether age affected the function of the vestibular system, our research team administered balance and motion tests to 105 healthy people ranging from 18 to 80 years old and measured their vestibular thresholds (“threshold” refers to the smallest possible motion administered that the subject is able to perceive correctly).

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Neuroimaging Detects Chemical Disturbances in Stuttering

MedicalResearch.com Interview with:
Joseph O’Neill, PhD
Division of Child and Adolescent Psychiatry
University of California–Los Angeles Semel Institute for Neuroscience
Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Stuttering seriously diminishes quality of life. While many children who stutter eventually grow out of it, stuttering does persist into adulthood in many others, despite treatment. Like earlier investigators, we are using neuroimaging to explore possible brain bases of stuttering, aiming, eventually, to improve prognosis. What’s novel is that our study deploy neuroimaging modalities– arterial spin labelling and, in this paper, magnetic resonance spectroscopy (MRS)– not previously employed in stuttering. MRS offers prospects of detecting possible neurochemical disturbances in stuttering.

The MRS results showed differences in neurometabolite– brain chemicals– levels between people who stutter (adults and children) and those who don’t in many brain regions where other neuroimaging has also observed effects of stuttering. In particular, MRS effects were apparent in brain circuits where our recent fMRI work detected signs of stuttering, circuits subserving self-regulation of speech production, attention and emotion. This reinforces the idea that stuttering has to do with how the brain manages its own activity along multiple dimensions: motivation, allocation of resources, and behavioral output.

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