Author Interviews, Gender Differences, Neurological Disorders, Psychological Science / 20.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31375" align="alignleft" width="114"]Lise Eliot PhD Associate Professor of Neuroscience Chicago Medical School Rosalind Franklin University North Chicago, IL 60064 Dr. Lise Eliot[/caption] 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.
Author Interviews, Critical Care - Intensive Care - ICUs, Emory, Neurological Disorders / 17.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31238" align="alignleft" width="100"]Andres Rodriguez Ruiz, MD</strong> Clinical Neurophysiology and Neurology Emory School of Medicine Dr. Andres Rodriguez Ruiz[/caption] 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.
Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 07.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31038" align="alignleft" width="200"]Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, PB 2040 Rotterdam Prof Rogier Q Hintzen[/caption] 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.
Author Interviews, Neurological Disorders, Radiology / 06.01.2017

MedicalResearch.com Interview with: [caption id="attachment_30973" align="alignleft" width="150"]Jay Desai, M.D. Neurologist, Children’s Hospital Los Angeles Assistant Professor, Keck School of Medicine of USC Dr. Jay Desai[/caption] 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.
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.
Author Interviews, Immunotherapy, Multiple Sclerosis, NEJM, University Texas / 22.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30711" align="alignleft" width="160"]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,[/caption] 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.
Author Interviews, Biomarkers, Multiple Sclerosis / 19.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30641" align="alignleft" width="200"]Charles Bangham PhD ScD Division of Infectious Diseases, Department of Medicine Imperial College London London, UK Dr. Charles Bangham[/caption] 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.
Author Interviews, Nature, Neurological Disorders, Technology / 16.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30535" align="alignleft" width="118"]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[/caption] 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.
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 .
Author Interviews, Diabetes, Parkinson's, Science / 09.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30315" align="alignleft" width="200"]Patrik Brundin, M.D., Ph.D. Director, Center for Neurodegenerative Science Van Andel Research Institute Dr. Patrik Brundin[/caption] 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.
Author Interviews, Neurological Disorders / 07.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30297" align="alignleft" width="150"]Dr. Paul Davies PhD Tufts University School of Medicine Department of Neuroscience Boston, MA 02111 Dr. Paul Davies[/caption] 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.
Author Interviews, Brigham & Women's - Harvard, ENT, Neurological Disorders / 30.11.2016

MedicalResearch.com Interview with: [caption id="attachment_30046" align="alignleft" width="150"]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[/caption] 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).
Author Interviews, JAMA, Neurological Disorders, Radiology, UCLA / 28.11.2016

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.
Author Interviews, Neurological Disorders, Ophthalmology, Pediatrics / 23.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29930" align="alignleft" width="167"]Marius George Linguraru, DPhil, MA, MB Principal Investigator Associate Professor of Pediatrics and Radiology George Washington University School of Medicine and Health Sciences Children’s National Health System Washington, DC Dr. Marius George Linguraru[/caption] Marius George Linguraru, DPhil, MA, MB Principal Investigator Associate Professor of Pediatrics and Radiology George Washington University School of Medicine and Health Sciences Children’s National Health System Washington, DC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the central nervous with an incidence of one in 3,000 births. Nearly one in five children with NF1 develops an optic pathway glioma (OPG), a low-grade tumor of the anterior visual pathway (i.e., optic nerves, chiasm and tracts). These tumors are not amenable to surgical resection and can cause permanent vision loss ranging from a mild decline in visual acuity to complete blindness. Only half of children with NF1-OPGs will experience vision loss, typically between 1 to 6 years of age. The other half will never lose vision or require treatment. All previous studies have consistently demonstrated that the change in NF1-OPG size is not related to the clinical outcome. For example, the optic pathway glioma size may be stable or even decrease, yet the vision will decline. Alternatively, the OPG size may increase, yet the clinical outcome remains stable or even improves. As no imaging or clinical features can identify which children with NF1-OPGs will ultimately lose vision, clinicians struggle to follow these children and decide when to intervene. We used quantitative imaging technology to accurately assess in magnetic resonance imaging (MRI) the total volume of OPGs in NF1. We also determined the retinal nerve fiber layer thickness in these children, a measure of axonal degeneration and an established biomarker of visual impairment. The results were outstanding, as we showed for the first time that the volume of an optic pathway glioma is indeed correlated with the likelihood of vision loss in children with Neurofibromatosis type 1.
ADHD, Author Interviews, JAMA, Neurological Disorders, NIH / 22.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29904" align="alignleft" width="200"]Gustavo Sudre, PhD Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch National Human Genome Research Institute Bethesda, Maryland Dr. Gustavo Sudre[/caption] Gustavo Sudre, PhD Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch National Human Genome Research Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Response: ADHD is the most common childhood neuropsychiatric disorder, affecting 7-9% of school age children. It is highly heritable (h2=0.7), but few risk genes have been identified. In this study, we aimed to provide quantitative brain-based phenotypes to accelerate gene discovery and understanding. ADHD is increasingly viewed as resulting from anomalies of the brain’s connectome. The connectome is comprised of the structural connectome (white matter tracts joining different brain regions) and the functional connectome (networks of synchronized functional activity supporting cognition). Here, we identified features of the connectome that are both heritable and associated with ADHD symptoms.
Author Interviews, Immunotherapy, Multiple Sclerosis / 22.11.2016

MedicalResearch.com Interview with Ralph Kern, M.D. Senior vice president, Worldwide Medical Biogen MedicalResearch.com: What is the background for this study? Response: Previously reported clinical trials of daclizumab demonstrated significant efficacy across clinical and MRI measures, compared to placebo and interferon beta-1a 30 mcg intramuscular (IM) injection, and established the therapy’s safety profile for up to two to three years. These trials were the basis for approval by health authorities in the United States, European Union and Australia. Daclizumab is a once-monthly, self-administered, subcutaneous therapy for relapsing forms of MS (RMS). At ECTRIMS we presented the first interim results from EXTEND, a long-term extension study. EXTEND is an ongoing multicenter, open-label study to evaluate the safety and efficacy of daclizumab treatment in more than 1,500 patients with RMS. This interim ECTRIMS analysis includes up to five years of data from patients who were previously enrolled in DECIDE. DECIDE was a Phase 3 study evaluating the effects of daclizumab relative to interferon beta-1a IM. In the new analysis, patients who were treated with interferon beta-1a IM for two to three years in DECIDE switched to daclizumab when they enrolled in EXTEND, and were compared to daclizumab patients treated continuously in both DECIDE and EXTEND.
Author Interviews, JAMA, Neurological Disorders, Parkinson's / 21.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29406" align="alignleft" width="120"]Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College Dr. Adolfo Ramirez Zamora[/caption] Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias. Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease.
ALS, Author Interviews, NEJM, Technology / 19.11.2016

MedicalResearch.com Interview with: Mariska Van Steensel PhD Nick F. Ramsey, Ph.D. Department of Neurology and Neurosurgery Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who are severely paralyzed due to for example ALS or brain stem stroke are often unable to speak (also called ‘ Locked-in State'), and therefore need assistive devices, such as an eye tracker, for their communication. When these devices fail (e.g. due to environmental lighting or eye movement problems), people may indicate yes or no with eye blinks in response to closed questions. This leaves patients in a highly dependent position, since questions asked may or may not represent their actual wish or comment. In the current study, we used a technology called brain-computer interfacing (BCI), to allow a patient with late-stage amyotrophic lateral sclerosis (ALS) to control a communication device using her brain signals. The patient was implanted with subdural electrodes that covered the brain area that is normally responsible for hand movement. The electrodes were connected with wires, subcutaneously, to an amplifier/transmitter device that was placed subcutaneously under the clavicle. The patient was able to generate a signal equivalent to a mouse-click with this brain-computer interface by attempting to move her hand, and used it to make selections of letters or words on her communication device, with high accuracy and a speed of 2 letters per minute. She used the brain-computer interface system to communicate whenever she was outside, as her eye-tracker device does not function well in that situation.
Author Interviews, Brigham & Women's - Harvard, Neurological Disorders / 17.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29729" align="alignleft" width="162"]Michael D. Fox, MD, PhD Assistant Professor in Neurology Berenson-Allen Center for Noninvasive Brain Stimulation Division of Cognitive Neurology, Department of Neurology Beth Israel Deaconess Medical Center Boston, MA Dr. Michael Fox[/caption] Michael D. Fox, MD, PhD Assistant Professor in Neurology Berenson-Allen Center for Noninvasive Brain Stimulation Division of Cognitive Neurology, Department of Neurology Beth Israel Deaconess Medical Center Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Consciousness is thought to be composed of arousal plus awareness, but no one knows where these processes live in the human brain. We took a unique approach to this question by studying human brain lesions that disrupt consciousness and cause coma. We found one small spot in the brainstem that was specific for coma (i.e. lesions that hit this spot caused coma while lesions that didn’t hit the spot did not cause coma). In other words, there was one spot in the human brainstem that, when lesioned, disrupted arousal and caused coma We then looked at the connectivity of that brainstem spot, and found that it was connected to two cortical regions previously implicated in awareness. These cortical regions also contained a unique type of brain cell thought only to be present in higher order mammals that are self-aware. To confirm our findings, we looked at the integrity of our network in patients with disorders of consciousness (e.g. persistent vegetative state) and found selective disruption of this network.
Author Interviews, Hepatitis - Liver Disease, JAMA, Neurological Disorders / 08.11.2016

MedicalResearch.com Interview with: Philip Van Damme, MD, PhD Department of Neurology and Department of Neurosciences, Experimental Neurology KU Leuven University of Leuven VIB, Vesalius Research Center, Leuven, Belgium Philip Van Damme, MD, PhD Department of Neurology and Department of Neurosciences, Experimental Neurology KU Leuven University of Leuven VIB, Vesalius Research Center, Leuven, Belgium MedicalResearch.com: What is the background for this study? Response: The hepatitis E virus (HEV) has been discovered more that 60 years ago. Its clinical manifestations are usually self-limiting and mild. More recently, several immune-mediated neurological complications of this virus have been described, such as the Guillain-Barre syndrome (GBS) and neuralgic amyotrophy. In this study, we investigated the frequency of a preceding HEV infection in patients presenting with a GBS syndrome or one of its less common disease variants. At the same time, we tested for other known pathogens known to be associated with GBS.
Author Interviews, Neurological Disorders / 04.11.2016

MedicalResearch.com Interview with: [caption id="attachment_29409" align="alignleft" width="200"]Researchers suggest that there are unique areas in the brain’s neuronal network that can serve as the conscious complex of the brain, enabling conscious activity Researchers suggest that there are unique areas in the brain’s neuronal network that can serve as the conscious complex of the brain, enabling conscious activity. Credit: Nir Lahav,     Eti Ben Simon[/caption] Nir Lahav Physics Department Bar-Ilan University in Israel MedicalResearch.com: What is the background for this study? Response: Our brain is a very complex network, with approximately 100 billion neurons and 100 trillion synapses between the neurons. The question is how can we cope with this enormous complexity? Ultimately, scientists seek to understand how a global phenomenon such as consciousness can emerge from our neuronal network. We used network theory in order to cope with this complexity and to determine how the structure of the human cortical network can support complex data integration and conscious activity. Previous studies have shown that the human cortex is a network with small world properties, which means that it has many local structures and some shortcuts from global structures which connect faraway areas (similar to the difference between local buses and cross-country trains). The cortex also has many hubs, which are nodes that have a high number of links (like central stations), that are also strongly interconnected between themselves, making it easy to travel between the brain's information highways.But in order to examine how the structure of the network can support global emerging phenomena, like consciousness, we need to look not only in the different nodes. We need to check global areas with lots of nodes. That's why we applied a network analysis called k-shell decomposition. This analysis takes into account the connectivity profile of each node making it easy to uncover different neighborhoods of connections in the cortical network, we called shells. The most connected neighborhood in the network is termed the network's nucleus. until today scientists were only interested in the network's nucleus, but we found that these different shells can hold important information about how the brain integrates information from the local levels of each node to the entire global network. For the first time we can build a comprehensive topological model of our cortex.
ALS, Antioxidants, Author Interviews, Columbia, Inflammation, JAMA, Nutrition / 26.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29061" align="alignleft" width="165"]Dr. Jeri Nieves PhD Director of bone density testing New York's Helen Hayes Hospital Dr. Jeri Nieves[/caption] Dr. Jeri Nieves PhD Director of bone density testing New York's Helen Hayes Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Amyotrophic lateral sclerosis (ALS) is a devastating severe neurodegenerative disorder that causes progressive muscle atrophy, paralyses, and eventual respiratory failure. Our objective was to evaluate the associations between nutrition and severity of ALS around the time of diagnosis. This was a cross-sectional analysis of data from a multicenter cohort of 302 patients with ALS. We assessed nutrient intake using a modified Block Food Frequency Questionnaire. The outcomes were respiratory function (measured using percentage forced vital capacity; FVC%) and functional performance measured by ALS Functional Rating Scale–Revised (ALSFRS-R), both considered important indicators of the severity of ALS. Results of the regression analysis were that higher intakes of antioxidants and carotenes from vegetable intake were associated with higher ALSFRS-R scores or better %FVC. We used a novel analysis to evaluate the diet as a whole and found that higher intakes of antioxidants, fiber from grains, vegetables, fruit, eggs, fish, and poultry were all associated with higher function in patients with ALS. However, milk and lunch meats were associated with lower measures of function. These consistent results from two different statistical analyses indicate that diet may help minimize the severity of ALS. Perhaps these findings point to the role of oxidative stress in ALS severity. In summary, increased consumption of antioxidant nutrients, foods high in carotenoids and fiber, vegetables and fruits, poultry and fish are associated with better function around the time of ALS diagnosis.
Author Interviews, Neurological Disorders, Pulmonary Disease / 24.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28937" align="alignleft" width="118"]Paolo Prandoni, M.D., Ph.D. Dr.Paolo Prandoni[/caption] Paolo Prandoni, M.D., Ph.D. and Department of Cardiovascular Sciences Vascular Medicine Unit University of Padua, Padua [caption id="attachment_28938" align="alignleft" width="82"]Sofia Barbar, M.D Dr.Sofia Barbar[/caption] Sofia Barbar, M.D Department of Internal and Emergency Medicine Civic Hospital of Camposampiero Camposampiero MedicalResearch.com: WhaWhat are the main findings? Response: Syncope is defined as a sudden loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. According to the most recent guidelines, syncope can be classified as neurally-mediated, due to orthostatic hypotension and cardiovascular. Syncope is frequent in general population and represents up to 2% of all attendances in Emergency Department in Europe. The initial approach is unable to identify a plausible cause for syncope in 25-30% of cases and approximately 40% of syncope referred to an Emergency Department is then admitted to the hospital. Pulmonary embolism (PE) is an obstruction in the pulmonary arteries interfering with both blood circulation and gas exchange and therefore representing a potentially life-threatening event. Clinical features of PE are extremely variable. Available guidelines on syncope management consider PE as an infrequent cardiovascular cause of syncope. However, the true prevalence of pulmonary embolism in syncope-patients it is actually unknown. Moreover a workup for PE diagnosis in these patients is not suggested in the current guidelines.
Alzheimer's - Dementia, Author Interviews, JAMA, Neurological Disorders / 20.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29020" align="alignleft" width="132"]Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London Dr David Lynch[/caption] Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2011 it was discovered that mutations in a gene called CSF1R cause a rare syndrome of early onset dementia often accompanied by movement disorders, spasticity and seizures, which is named adult onset leukoencephalopathy with axonal spheroids (ALSP). The hallmarks of ALSP are a characteristic appearance on MRI imaging and findings in brain pathological specimens - axonal swellings or 'spheroids'. We manage a multidisciplinary group with expertise in leukoencephalopathies and have previously identified patients with mutations in CSF1R. However, we also found patients with a syndrome typical of ALSP who did not carry mutations in CSF1R. In this study, we showed that some of these patients carry recessive mutations in a different gene, AARS2. This included a patient with characteristic axonal spheroids in brain tissue and typical ALSP clinical and imaging features.
Author Interviews, Parkinson's, Pharmacology / 28.09.2016

MedicalResearch.com Interview with: Dr. Christina Friedrich Chief Engineer, PhysioPD Rosa & Co. LLC MedicalResearch.com: What is the background for this study? Response: Elan was developing compounds for the treatment of Parkinson’s Disease. The compounds were designed to modify negative effects of alpha-synuclein on neurotransmitter vesicle trafficking, but these effects are poorly understood. Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model architecture to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking, memorialize and communicate the current state of knowledge within Elan, and to recommend experiments to test hypotheses, resolve uncertainties and identify and prioritize potential targets.
Author Interviews, Multiple Sclerosis, Pharmacology / 27.09.2016

MedicalResearch.com Interview with: Marcia Kayath, MD Vice President and Head US Clinical Development and Medical Affairs US General Medicines Novartis Pharmaceuticals Corporation MedicalResearch.com: What is the background for this study? What are the main findings? Response: Injectable disease-modifying therapies (DMTs) are typically used first-line in patients with multiple sclerosis (MS), but discontinuation of injectable DMTs is common, especially within the first 12 months of treatment1,2. PREFERMS is the largest, prospective, randomized, active-controlled, open-label study to evaluate patient retention in patients with relapsing-remitting multiple sclerosis (RRMS). In the 12-month, Phase IV study, a total of 875 patients were randomized (1:1) to Gilenya® (fingolimod) 0.5 mg or to a pre-selected injectable DMT (IFNβ-1a, IFNβ-1b or glatiramer acetate), and followed up quarterly for 12 months3. After a minimum of 3 months of treatment, a single on-study treatment switch was allowed, however, switches due to efficacy or safety were allowed (based on patient-doctor consultation) at any month following randomization3. The primary endpoint was to compare the patient retention on randomized treatment over 12 months3. This study was powered for the primary endpoint (retention rate)3. The study was not powered to detect the treatment difference in the secondary efficacy endpoints or treatment effects related to switching study medication3.
Author Interviews, Biomarkers, JAMA, NIH, Parkinson's / 26.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28339" align="alignleft" width="200"]Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland Dr. Yong Cheng[/caption] Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland MedicalResearch.com: What is the background for this study? Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.
Author Interviews, Epilepsy, JAMA, Mayo Clinic, Neurological Disorders / 23.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28300" align="alignleft" width="180"]Brian Nils Lundstrom, MD, PhD Department of Neurology Mayo Clinic Rochester, Minnesota Dr. Brian Lundstrom[/caption] Brian Nils Lundstrom, MD, PhD Department of Neurology Mayo Clinic Rochester, Minnesota MedicalResearch.com: What is the background for this study? What are the main findings? Response: About as many people have drug-resistant focal epilepsy as have multiple sclerosis, and treatment options are limited. This study describes an alternative treatment option that has proven very helpful for the majority of participants. Electrical stimulation is delivered continuously via implanted electrodes to the region of brain where seizures start. The electrical stimulation decreases the seizure-related discharges from the brain, and for about 40% of patients their disabling seizures were completely stopped.
Author Interviews, Neurological Disorders / 31.08.2016

MedicalResearch.com Interview with: Sanne Kikkert, DPhil student FMRIB Centre, University of Oxford Oxford, United Kingdom MedicalResearch.com: What is the background for this study? Response: One of the most mysterious questions about the brain’s ability to adaptively change to new circumstances is: what happens to the brain once a key input is lost (e.g. through amputation)? It has been thought that the hand representation in the brain, located in the primary somatosensory cortex, is maintained by regular sensory input from the hand. Indeed, textbooks teach that any sensory representation in the brain will be ‘overwritten’ if its primary input stops. Following this explanation, people who have undergone hand amputation would show extremely low or no activity related to its original focus in the brain area of the missing hand. However, we know that amputees often experience phantom sensations from their missing hand, such that when asked to move a phantom finger they can ‘feel’ that movement. We previously showed that we can trace some activity in the missing hand brain area when amputees move their phantom hand. In this study, we were interested in finding how the representation of a missing hand is stored in the brain.
Author Interviews, Genetic Research, Neurological Disorders / 26.08.2016

MedicalResearch.com Interview with: Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852Lee Henderson, Ph.D. CEO, Vybion, Inc. Ithaca, NY 14852 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons.