Author Interviews, Epilepsy, JAMA, Karolinski Institute, OBGYNE, Pediatrics, Weight Research / 06.04.2017

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. (more…)
Author Interviews, Brain Injury, Neurological Disorders, Pediatrics / 06.04.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Multiple Sclerosis / 05.04.2017

MedicalResearch.com Interview with: 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. (more…)
ALS, Author Interviews, Biomarkers, Neurology / 24.03.2017

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 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. (more…)
Author Interviews, Neurological Disorders / 23.03.2017

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. (more…)
Author Interviews, Cognitive Issues, Multiple Sclerosis, NYU / 01.03.2017

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 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. (more…)
ADHD, Author Interviews, Lancet, MRI, Neurological Disorders / 01.03.2017

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. (more…)
Author Interviews, Epilepsy, Pharmacology / 28.02.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Neurological Disorders, Zika / 19.02.2017

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 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. (more…)
Author Interviews, JAMA, Multiple Sclerosis, Neurology / 18.02.2017

MedicalResearch.com Interview with: 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. (more…)
ALS, Author Interviews, Genetic Research, JAMA / 15.02.2017

MedicalResearch.com Interview with: Prof. Dr. Christine Van Broeckhoven PhD DSc Professor in Molecular Biology and Genetics, University 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. (more…)
Author Interviews, Heart Disease, JAMA, Neurological Disorders, Stroke / 13.02.2017

  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. (more…)
ALS, Author Interviews, Brain Injury, Mental Health Research, PLoS, Technology / 12.02.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Neurological Disorders, Pharmacology / 12.02.2017

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 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. (more…)
Author Interviews, Genetic Research, Nature, Neurological Disorders / 31.01.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Education, Neurological Disorders, Neurology, University of Pittsburgh / 30.01.2017

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 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. (more…)
Author Interviews, Heart Disease, Neurological Disorders, Pediatrics, Science, Stem Cells / 27.01.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Mental Health Research, Neurological Disorders, Psychological Science / 27.01.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Gender Differences, Neurological Disorders, Psychological Science / 20.01.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Emory, Neurological Disorders / 17.01.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 07.01.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Neurological Disorders, Radiology / 06.01.2017

MedicalResearch.com Interview with: 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. (more…)
Aging, Author Interviews, Neurological Disorders, Yale / 22.12.2016

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. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis, NEJM, University Texas / 22.12.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Biomarkers, Multiple Sclerosis / 19.12.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Nature, Neurological Disorders, Technology / 16.12.2016

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 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. (more…)
Author Interviews, Biomarkers, Infections, JAMA, Neurological Disorders / 12.12.2016

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 . (more…)
Author Interviews, Diabetes, Parkinson's, Science / 09.12.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Neurological Disorders / 07.12.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Brigham & Women's - Harvard, ENT, Neurological Disorders / 30.11.2016

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 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). (more…)