Author Interviews, Microbiome, Multiple Sclerosis / 05.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23164" align="alignleft" width="85"]Professor JF Cryan PhD Department of Anatomy and Neuroscience APC Microbiome Institute University College Cork Cork, Ireland Prof. John Cryan[/caption] Professor JF Cryan PhD Department of Anatomy and Neuroscience APC Microbiome Institute University College Cork Cork, Ireland MedicalResearch.com: What is the background for this study? What are the main findings?  Prof. Cryan: Over the past decade there has been an ever growing body of preclinical studies that highlight an essential role of the gut microbiota in many aspects of physiology including and perhps most surprtisingly the brain . Germ-free animals are one useful approach used to establish causality in gut microbiota-brain relationships. This model has been extremely useful in establishing that the microbiota is essential for appropriate stress responsibility, anxiety-like behaviours, neurogenesis, blood-brain barrier function and microglia activity. From these findings we can see that there is a clear cut role for the microbiota in CNS developmental processes. Here we wanted to investigate using next generation sequencing, as we had done previously in the amygdala what impact life without microbes has on transcriptional regulation in the prefrontal cortex, a brain region essential in many aspects of emotional behaviour. What we uncovered from this was that there was a large number of dysregulated genes in germ-free animals that have a direct role in myelination. We found increased expression levels of genes that encode for structural proteins that are key in forming the myelin sheath. We followed up this finding with transmission electron microscopy to identify whether this marked increase in myelin related gene expression was functional at a structural level. What we found was germ-free myelinated axons in the prefrontal cortex were hypermyelinated (lower g-ratio), they had thicker myelin sheaths compared to conventionally raised mice. Additionally we also had germ-free colonized animals, animals that were born germ-free but have been colonized with a conventional microbiome early in life. These animals displayed no change in myelin related gene expression and appeared to be indistinguishable from the conventional animals. However, at the protein levels they appeared to have increased myelin protein like germ-free mice. This could be due to the fact that these mice were germ-free for at least 3 weeks of life and the hypermyelinated axons had already been established before colonization. Really this shows that we can still target the microbiota in later life that can have an impact of myelin gene regulation.
Author Interviews, Dermatology, JAMA, Parkinson's / 21.03.2016

MedicalResearch.com Interview with: [caption id="attachment_21019" align="alignleft" width="200"]Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark Dr. Alexander Egeberg[/caption] Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes. Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells. Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson's disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson's disease.
Author Interviews, Diabetes, JAMA, Multiple Sclerosis / 10.03.2016

MedicalResearch.com Interview with: Jorge Correale MD Department of Neurology, Institute for Neurological Research Dr Raúl Carrea Buenos Aires, Argentina MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Correale: First it is now well known that in parallel to the specific treatment of Multiple Sclerosis, those comorbidities that worsen the course of the disease should be treated. For example, cardiovascular diseases. Moreover there are in vitro and in animal models evidence of an anti-inflammatory role of compounds investigated in this publication evidence.
Author Interviews, Lancet, Neurological Disorders, Pain Research / 07.03.2016

MedicalResearch.com Interview with: Nadine Attal, MD PhD Professeur associée de l'UVSQ INSERM U 987 et CETD CHU Ambroise Paré 92100 Boulogne-Billancourt MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Attal: The background for this study is based on the findings of experimental studies in animals and healthy subjects indicating that botulinum toxin type A  (BTX-A) may have analgesic activity independent of its effect on muscle tone. BTX-A has been reported to have analgesic effects against peripheral neuropathic pain in prior trials, but the quality of the evidence was generally low, as it was derived mostly from small pilot studies and no study has evaluated the relevance of repeated administrations for the treatment of NP. Furthermore, the clinical profiles of the patients responding to BTX-A have not been fully characterized. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Attal: They should take away that two repeated subcutaneous administrations of botulinum toxin type A are effective in peripheral  neuropathic pain but mostly in patients with allodynia and/or limited thermal deficits. BTX-A also appears to be particularly effective on paroxysmal pain (ie electric shock like pain). Finally, the efficacy of a second administration of BTX-A is enhanced over the first injection.
Author Interviews, BMJ, Coffee, Karolinski Institute, Multiple Sclerosis / 04.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22362" align="alignleft" width="200"]Anna Hedström PhD student Anna Hedström PhD student[/caption] Anna Hedström PhD student Karolinski Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies on the influence of coffee consumption on multiple sclerosis (MS) risk have yielded inconclusive results, perhaps largely due to statistical power problems since these studies comprised few cases. Caffeine consumption has a protective effect on neuroinflammation and demyelination in animal models of MS. We therefore aimed to investigate whether coffee consumption is associated with MS risk, using two large population-based case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a United States study comprising 1159 cases and 1172 controls). The risk of multiple sclerosis was reduced by approximately 30% among those who reported a high coffee consumption, around six cups daily, compared to those who reported no coffee consumption. The risk of multiple sclerosis decreased with increasing coffee consumption. Potentially important influential factors were taken into consideration, such as smoking and adolescent obesity.
Author Interviews, Neurological Disorders, Stroke / 29.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22199" align="alignleft" width="174"]Georgios Tsivgoulis , M.D., Ph.D., MSc, FESO Assistant Professor of Neurology University of Athens, Athens, Greece Visiting Associate Professor of Neurology Director of Stroke Research Department of Neurology University of Tennessee Health Science Center Dr. Georgios Tsivgoulis[/caption] Georgios Tsivgoulis , M.D., Ph.D., MSc, FESO Assistant Professor of Neurology University of Athens, Athens, Greece Visiting Associate Professor of Neurology Director of Stroke Research Department of Neurology University of Tennessee Health Science Center Medical Research: What is the background for this study? What are the main findings? Dr. Tsivgoulis: Literature data suggest that taking statins before an acute ischemic stroke may improve early outcomes including early neurological deterioration, mortality and disability in patients with acute ischemic stroke. However,the potential beneficial effect of statin pretreatment has never been investigated in acute ischemic stroke due to large artery atherosclerosis. The research question in this specific subgroup of ischemic stroke patients is of great importance, as large-artery atherosclerotic stroke carries the highest risk of early recurrent stroke in comparison to other acute ischemic stroke subtypes. Using prospectively collected data from over 516 consecutive patients with acute large-artery atherosclerotic stroke from seven tertiary-care stroke centers during a three-year period we found that statin pretreatment in patients with acute large-artery atherosclerotic stroke is associated with better early outcomes in terms of neurological improvement, disability, survival and stroke recurrence.
Author Interviews, Neurological Disorders, NYU/NYMC / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22115" align="alignleft" width="150"]Michael A. Long, PhD New York University School of Medicine Assistant Professor New York Stem Cell Foundation Robertson Neuroscience Investigator Dr. Michael Long[/caption] Michael A. Long, PhD New York University School of Medicine Assistant Professor New York Stem Cell Foundation Robertson Neuroscience Investigator Medical Research: What is the background for this study? Response: Speech is, of course, central to our everyday lives, and it is perhaps the most thoroughly studied human behavior.  That said, many aspects of how our brain produces speech are still poorly understood. Human brains are extremely complex, and many of the tools that are available to understand the function of the brain are quite limited.  Although we have a good idea of the brain regions involved in producing speech, our understanding of the roles that each area plays to enable us to produce words is much less clear. Medical Research: How did you become interested in this problem?  Response: I am a basic researcher focusing on the mechanisms that enable the brain to produce complex behaviors.  We primarily study the songbird brain, which contains several clearly defined areas that are dedicated to producing the song.  Through careful study, many research groups have discovered how these areas are working together to produce the song.  I realized that this kind of perspective may be useful to further our understanding of human speech production. Medical Research: How did you translate the findings from the songbird brain to the human brain? Response: Many years ago, when I was a postdoc with Michalel Fee at MIT, I used a small head-mounted cooling device to selectively lower the temperature of specific brain regions in the songbird by a few degrees.  To our surprise and delight, the cooling of a specific brain area – called HVC – resulted in a slowing of the tempo of that song.  From this finding, we realized that HVC was a key timing center for singing, and by cooling that ‘clock’, the song that was produced happened more slowly. When I established my own lab at NYU, I reached out Dr. Matthew Howard’s Neurosurgery group at the University of Iowa because of his impressive history of making fundamental discoveries about human brain function.  There I met Dr. Jeremy Greenlee, and we discussed using a cooling approach for understanding human speech.  Since 2011, we worked with 22 patients that were undergoing neurosurgery for either epilepsy or tumor removal.  Patients were asked to recite simple lists of words, like the days of the week, while a device with a footprint about the size of a quarter would cool different places along the surface of the brain. 
Author Interviews, Diabetes, Neurological Disorders, Yale / 26.02.2016

MedicalResearch.com Interview with: [caption id="attachment_22111" align="alignleft" width="200"]Sabrina Diano, Ph.D. Professor Depts. Ob/Gyn, Neuroscience and Comparative Medicine Associate Chair for Faculty Development Dept Ob/Gyn and Reproductive Sciences Program in Cell Signaling and Neurobiology of Metabolism Yale University School of Medicine and Graduate School Dr. Sabrina Diano[/caption] Sabrina Diano, Ph.D. Professor, Depts. Ob/Gyn, Neuroscience and Comparative Medicine Associate Chair for Faculty Development Dept Ob/Gyn and Reproductive Sciences Program in Cell Signaling and Neurobiology of Metabolism Yale University School of Medicine and Graduate School  Medical Research: What is the background for this study? What are the main findings? Dr. Diano: We have been studying the intracellular mechanisms that regulate glucose sensing by the brain. We found that in a specific area of the brain (called ventromedial nucleus of the hypothalamus) a small group of neurons (the brain cells) are able to sense increased glucose levels in the blood via their mitochondria, the energy powerhouse of the cells. This mitochondrial change enables these neurons to get activated, which in turn, results in a reduction of  glucose levels in the blood due to an increased muscles glucose utilization.
Author Interviews, Compliance, Neurological Disorders, Stroke / 23.02.2016

MedicalResearch.com Interview with: Dr-William-Patrick-Neil William P. Neil, MD Vascular Neurologist SCPMG Regional Stroke Champion Neurology    Medical Research: What is the background for this study? Dr. Neil: Stroke survivors are less likely to have a recurrent stroke, or other complications if they take their medications as prescribed by their doctor. Mail order pharmacies are increasingly being used to deliver medications for a variety of diseases, and their use is associated with better medication adherence.  We wanted to see whether stroke patients who use mail-order pharmacies were more likely to have good medication adherence than those who used  local pharmacies. Medical Research: What are the main findings? Dr. Neil: We looked through a large electronic medical database in California, and found a total of 48,746 people discharged from the hospital with a stroke, and who also filled either a cholesterol medication or an anticoagulant (blood thinner). Of these, 136,722 refills were from a local pharmacy and 68,363 were by mail. Overall, patients were adherent to the medications 46.5% of the time if they picked up the medication from the pharmacy and 74% of the time if they had prescriptions mailed to them.
Author Interviews, Epilepsy / 21.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21891" align="alignleft" width="153"]Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX Dr. Samba Reddy[/caption] Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX Medical Research: What is the background for this study? What are the main findings? Dr. Reddy: Neurosteroids are a group of neuroactive compounds present in the brain. They are known to modulate ionotropic post-synaptic GABA-A receptors, which are the primary mediators of fast inhibitory neurotransmission in the brain. Hence, the neurosteroid—GABA-A receptor system is a critical axis for controlling neuronal excitability in certain brain disorders, such as anxiety and epilepsy. There is new evidence that such neurosteroids can strongly activate extrasynaptic GABA-A receptors, which are located outside of the synapses mainly on soma, dendrites and axons. However, the neurosteroid structure requirement for functional activation of extrasynaptic receptors remains largely unexplored.  In this study, we identified a consensus neurosteroid pharmacophore model at extrasynaptic GABA-A receptors for activation of tonic current and seizure protection.
Author Interviews, Epilepsy, Neurological Disorders, Stroke / 20.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21726" align="alignleft" width="96"]Alexander Merkler, MD Fellow in neuro critical care Weill Cornell Medical College and New York-Presbyterian Hospital, New York Dr. Alexander Merkler[/caption] Alexander Merkler, MD Fellow in neuro critical care Weill Cornell Medical College and New York-Presbyterian Hospital, New York Medical Research: What is the background for this study? What are the main findings? Dr. Merkler:  Patients with stroke often ask about what type of problems they may expect in the future. As neurologists, we often warm our patients about the risk for recurrent stroke, infections, clots, eating difficulty, and depression. Although seizures are a well-known complication of stroke, there was little data regarding the long-term rate of seizures in patients who have a stroke. Therefore, we sought to evaluate the long-term risk of seizures following stroke in order to better advise physicians and patients on the likelihood of developing seizures after suffering a stroke. We identified over 600,000 patients with stroke and found that the rate of seizures after stroke is high – 15.3% of all patients with stroke will develop seizures. Patients who have hemorrhagic stroke face an even higher rate of seizures – 24% of patients with hemorrhagic type stroke will develop seizures. The rate of seizures after ischemic stroke was significantly higher than previous literature - 13.5% of patients with an ischemic stroke had a seizure in our study.
Author Interviews, Cleveland Clinic, Lancet, Multiple Sclerosis / 16.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21655" align="alignleft" width="155"]Dr Jeffrey A Cohen MD Neurological Institute Cleveland Clinic, Cleveland OH 44195, USA Dr. Jeffrey Cohen[/caption] Dr Jeffrey A Cohen MD Mellen Center, Neurological Institute Cleveland Clinic, Cleveland OH 44195, USA Medical Research: What is the background for this study? What are the main findings? Dr. Cohen: Fingolimod, a non-selective sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral medication approved to treat relapsing multiple sclerosis.  Though generally well tolerated, fingolimod’s first dose cardiac effects and other potential adverse effects complicate its use.  Ozanimod is a selective S1PR modulator with several other potentially advantageous pharmacologic properties. The results of phase 2 RADIANCE trial were recently published.  In this trial, participants were randomized to placebo (n=88), ozanimod 0.5 mg (n=87), or ozanimod 1 mg (n=83) PO once daily for 24 weeks.  The mean cumulative number of gadolinium-enhancing lesions on monthly MRI scans at weeks 12-24, the primary endpoint, was reduced from 11.1 +/- 29.9 with placebo to 1.5 +/- 3.7 with ozanimod 0.5 mg and 1.5 +/- 3.4 with ozanimod 1 mg (both p<0.0001).  Other MRI endpoints supported the primary endpoint.  Ozanimod was well tolerated with good safety.  Importantly, the dose up-titration protocol effectively mitigated first dose cardiac effects.
Author Interviews, Epilepsy, Lancet, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21621" align="alignleft" width="160"]Dr. Michael Privitera MD Professor of the Department of Neurology and director of the Epilepsy Center University of Cincinnati Neuroscience Institute Dr. Michael Privitera[/caption] Dr. Michael Privitera MD Professor of the Department of Neurology and director of the Epilepsy Center University of Cincinnati Neuroscience Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Privitera: Generic substitution of medications has saved the American health care system billions of dollars per year. However, based on a series of uncontrolled studies, patients and clinicians share concerns that generic substitution of antiepileptic drugs may lead to loss of efficacy or emergence of adverse effects. To answer this question we undertook a prospective, randomized study that tested bioequivalence of two generic products of the antiepileptic drug lamotrigine. Lamotrigine was identified in several publications as a possible source of problems after generic switches. FDA studies test a single generic versus the brand name product in a single dose study in normal volunteers. We designed a study that would be most likely to show a difference between generics if one existed. We compared the two generic lamotrigine products showing the most difference in prior testing in patients with epilepsy taking the drug daily using rigorous pharmacokinetic methods. Each patient took each of the two generics for 2 four week periods. Our study showed the two generics were essentially indistinguishable and easily met bioequivalence standards. No patient had loss of seizure control or unexpected adverse effects.
Author Interviews, Neurological Disorders / 09.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21428" align="alignleft" width="160"]Prof. Daphna Joel PhD School of Psychological Sciences and Sagol School of Neuroscience Tel-Aviv University Prof. Daphna Joel[/caption] Prof. Daphna Joel PhD School of Psychological Sciences and Sagol School of Neuroscience Tel-Aviv University Medical Research: What is the background for this study? Prof. Joel: The aim of the PNAS study was to test the mosaic hypothesis, published in 2011 (“Male or female? Brains are intersex”), according to which there are no “male brains” and ‘female brains” but rather brains are composed of unique mosaics of features, some more common in males and other more common in females.  This hypothesis was build on animal data showing that the effects of sex on the brain may be different and even opposite under different environmental conditions (i.e., what is typical in one sex under some conditions may be typical in the other sex under other conditions). In the Phil.Trans. paper, we use a very simple mathematical illustration to explain why the existence of sex differences is not sufficient to conclude that there are two types of brain, and how the answer to this question depends on the prevalence of ‘mosaic’ brains. Medical Research: What are the main findings? Prof. Joel: In the PANS study we, found differences between brains from males and brains from females, as has previously been reported.  What we have done in addition, and no previous study has, is look whether brains are internally consistent, that is, have either only “male-end” features (i.e., features in the form more common in males compared to females) of only “female-end” features (i.e., features in the form more common in females compared to males). We found that internally consistent brains are much less common compared to ‘substantially variable’ brains (i.e., brains with both “female-end” and “male-end” features), and that the large majority of brains are composed of unique mosaic of “female-end”, “male-end”, and “intermediate” (i.e., common in both females and males) features.  On the basis of these findings we concluded that there are no “male brains” and “female brains”. In the Phil.Trans. paper we further suggest that human brains belong to a single highly heterogeneous population (see also Joel, 2011, Male or female? Brains are intersex), in which there may be differences between females and males in the frequencies of rare brain mosaics (e.g., brains with only “female-end” characteristics although rare in the population, are more common in females compared to males).
Author Interviews, Frailty, Hip Fractures, Parkinson's, PLoS / 08.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21392" align="alignleft" width="200"]Helena Nyström MD, PhD Candidate Department of Community Medicine and Rehabilitation Umeå University Umeå, Sweden Helena Nyström[/caption] Helena Nyström MD, PhD Candidate Department of Community Medicine and Rehabilitation Umeå University Umeå, Sweden Medical Research: What is the background for this study? Response: Parkinson’s disease (PD) has an insidious onset and the prodromal phase, preceding the onset of the characteristic PD symptoms, may last for decades. Most prodromal signs previously reported are of non-motor type, such as sleep and mood disorders. However, recent studies have reported balance problems and an increased risk of accidental injuries in the last 3-5 years before diagnosis of Parkinson’s disease , and in a previous study we found a lower muscle strength at military conscription in men who were diagnosed with  Parkinson’s disease three decades later. In this study, we aimed to investigate if such subtle strength deficits may translate into an increased risk of fall-related injuries. Medical Research: What are the main findings? Response: The median study time was 20 years before the diagnosis of  Parkinson’s disease , and during this time more individuals with PD (18%) than controls (11.5%) had at least one fall-related injury. The risk was most increased in the last few years before the diagnosis of  Parkinson’s disease , but a difference between the groups appeared already a decade before the PD diagnosis. The risk of hip fracture was increased during the entire study time of 26 years before the diagnosis of Parkinson’s disease .
Author Interviews, Neurological Disorders, Zika / 06.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21356" align="alignleft" width="120"]Dr. Kenneth C. Gorson, MD President Elect GBS|CIDP Foundation International Global Medical Advisory Board Dr. Ken Gorson[/caption] Dr. Kenneth C. Gorson, MD President Elect GBS|CIDP Foundation International Global Medical Advisory Board Guillain-Barre syndrome (GBS) Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Medical Research: What is Guillain-Barré Syndrome? What are the main symptoms? Dr. Gorson: Guillain-Barré Syndrome (GBS) is an immune mediated disorder affecting the peripheral motor and sensory nerves and nerve roots, and is the most common cause of rapidly progressive generalized paralysis in western countries. It is characterized by acute or subacute, progressive, symmetrical limb weakness with distal numbness or tingling in the arms and legs, and reduced or absent deep tendon reflexes in previously healthy patients. Patients notice the sudden onset of difficulty walking, climbing stairs, carrying objects and impaired fine motor skills. Balance is impaired due to sensory loss or weakness and a minority of patients develop facial weakness, trouble speaking and swallowing, and double vision. Severely affected patients may require ventilator support due to respiratory muscle weakness. Symptoms worsen over days to weeks, and most patients reach a maximum deficit (nadir) by 4 weeks, followed by a plateau phase for weeks to months, and then a recovery phase over additional weeks to months. Approximately 80 percent of patients recover to walk with minimal or no residual symptoms or functional disability. Maximal improvement usually occurs by one year, but more severely affected patients may continue to observe subtle improvements for several years after symptom onset. In approximately two thirds of affected patients there is some preceding triggering event, classically a viral syndrome manifest as a transient upper respiratory or gastrointestinal illness with fever that resolves uneventfully prior to the onset of the neuropathy. Current evidence indicates the pathophysiology of GBS is related to molecular mimicry, where the patient's antibody response to the preceding infection interacts with a variety of antigens on peripheral nerve myelin or axons producing a generalized but multifocal inflammatory demyelinating process and associated axonal loss in some instances. The diagnosis is established with nerve conduction studies and electromyography, which shows features indicative of a demyelinating neuropathy affecting multiple motor nerves in the arms and legs. The cerebrospinal fluid protein level is elevated without a cellular response (cyto-albuminological dissociation) in up to 80 percent of patients when performed in the first week of the illness. Treatment is directed toward the immune response, and several large randomized controlled trials have demonstrated that intravenous immunoglobulin and plasma exchange hasten recovery, and both treatments have similar efficacy.
Author Interviews, Brigham & Women's - Harvard, Multiple Sclerosis, Neurological Disorders, Stem Cells / 26.01.2016

MedicalResearch.com Interview with: Zhigang He, PhD, BM Professor of Neurology  and Michela Fagiolini, PhD Assistant Professor of Neurology F.M. Kirby Neurobiology Center, Department of Neurology Children’s Hospital, Harvard Medical School Boston, MA 02115, USA

Medical Research: What is the background for this study? Drs. Fagiolini and He: Brain or spinal cord injury is still a major medical problem and there is no effective treatment of promoting functional recovery. A key issue is the nerve fibers, or axons, connecting different brain regions are damaged and cannot be repaired. For example, the axons in the optic nerve are the only channels transmitting visual signals from eye to brain. If damaged, our brain will not be able to receive visual signals and be blinded. Thus, a logical therapy should be to stimulate damaged axons to regrow to the targets and reconnect the eyes and brain. Studies in the past from us and others revealed several approaches of promoting the regrowth of injured axons, but it was unknown whether these regenerated axons could form functional connections and mediate functional recovery. Medical Research: What are the main findings? Drs. Fagiolini and He:  What we discovered in this study is that these regenerated axons could form functional connections, synapses, in the brain targets, but surprisingly fail to mediate behavioral visual function recovery. In mammals, many long projecting axons are insulated by lipid-enriched myelin sheets which could significantly speed up nerve conduction and facilitate the functional coordination of different brain regions during behavior. Interestingly, we found that different from intact optic nerves, these regenerated axons fail to be myelinated and thus possess poor conductance. When we treat these mice with compounds that can improve nerve conduction, we do observe partial yet significant functional recovery. Thus, there are at least two pieces of information from this study:
  • First, axon regrowth might not enough for functional recovery, nerve conduction could be another hurdle;
  • Second, the combination of these manipulations could serve a proof-of-principle example for achieving functional recovery.
ALS, Author Interviews / 22.01.2016

More on Alzheimer's Disease on MedicalResearch.com MedicalResearch.com Interview with: Sandra Anne Banack Institute for Ethnomedicine Jackson Hole, WY Medical Research: What is the background for this study? What are the main findings? Response: Villagers from the island of Guam had 50-100x the incidence rates of ALS when compared with Western populations. Although the disease on Guam  was first identified as ALS it is now known as ALS/PDC because it can also have clinical features of Parkinson’s and Alzheimer's diseases. The pathological features of this disease include brain tangles and amyloid plaques that are also the diagnostic features of Alzheimer's disease.  We found that an environmental neurotoxin causes brain tangles and amyloid deposits in an animal model. This is the first time that brain tangles, known technically as neurofibrillary tangles, have been created in an animal model along with the amyloid deposits. The animal model can be used to screen potential drugs for Alzheimer's and potentially other neurodegenerative diseases quicker and at a fraction of the cost and risk of current methods using human subjects. In addition, we found that L-serine significantly reduced the formation of brain tangles exposed to this toxin.
Author Interviews, JAMA, Neurological Disorders, Parkinson's / 20.01.2016

[caption id="attachment_20653" align="alignleft" width="132"]Professor Carl E Clarke Professor of Clinical Neurology and Honorary Consultant Neurologist Department of Neurology City Hospital Sandwell and West Birmingham Hospitals NHS Trust Birmingham UK Prof. Carl Clarke[/caption] More Interviews on Neurological Disorders on MedicalResearch.com MedicalResearch.com Interview with: Professor Carl E Clarke Professor of Clinical Neurology and Honorary Consultant Neurologist Department of Neurology City Hospital Sandwell and West Birmingham Hospitals NHS Trust Birmingham UK Medical Research: What is the background for this study? Dr. Clarke: Parkinson's disease causes problems with activities of daily living that are only partially treated by medication and occasionally surgery. Physiotherapy and occupational therapy services like Ck Physio are traditionally used later in the disease, but it is unclear whether they are clinically and cost-effective in Parkinson's disease. Medical Research: What are the main findings? Dr. Clarke: We performed a large pragmatic randomised trial to evaluate the clinical and cost-effectiveness of individualized physiotherapy and occupational therapy in Parkinson's disease. The PD REHAB trial was a multicenter, open label, parallel group, controlled efficacy trial. 762 patients with mild-moderate Parkinson’s disease were recruited from 38 sites across the United Kingdom. For patients with mild to moderate Parkinson disease, there were no clinically meaningful benefits in activities of daily living or quality of life associated with physiotherapy and occupational therapy.
Author Interviews, Neurological Disorders, Sleep Disorders / 19.01.2016

[caption id="attachment_20628" align="alignleft" width="200"]Dr. Andrew Lim MD, FRCPC Assistant Professor Neurology Sunnybrook Health Sciences Centre Toronto, ON Dr. Andrew Lim[/caption] More on Sleep Research on MedicalResearch.com MedicalResearch.com Interview with: Dr. Andrew Lim MD, FRCPC Assistant Professor Neurology Sunnybrook Health Sciences Centre Toronto, ON Medical Research: What is the background for this study? What are the main findings? Dr. Lim: Our group had previously shown that sleep fragmentation is associated with an increased risk of dementia and cognitive decline.  However, there were gaps in what we knew about underlying brain changes that may link sleep fragmentation with these neurological outcomes.  Experiments in mice and other animals suggested that damage to blood vessels may be one potential mechanism. In this study of 315 older individuals who had their sleep measured using wrist-watch like accelerometers, we found that individuals who had the most fragmented sleep were also more likely to have more severe damage to brain blood vessels and blood-vessel related brain injury at death.
Author Interviews, Lipids, Neurological Disorders / 18.01.2016

[caption id="attachment_20704" align="alignleft" width="200"]Noriko Osumi, DDS, PhD Director, Center for Neuroscience Professor, Department of Developmental Neuroscience Tohoku University School of Medicine Seiryo-machi, Aoba-ku, Sendai Japan Dr. Noriko Osumi[/caption] More on Lipids on MedicalResearch.com MedicalResearch.com Interview with: Noriko Osumi, DDS, PhD Director, Center for Neuroscience Professor, Department of Developmental Neuroscience Tohoku University School of Medicine Seiryo-machi, Aoba-ku, Sendai Japan  Medical Research: What is the background for this study? What are the main findings? Dr. Osumi: Omega-6 and omega-3 fatty acids are known to be important for brain growth. This is mainly because many researchers have shown that imbalance between these fatty acids during pregnancy causes several defects in future brain functions both in humans and rodents. Therefore, we asked the underlying mechanism how maternal intake of the omega-6 excess/omega-3 deficient dietary impairs brain development in mice using genetical rescue and comprehensive lipidomics together with neural stem cell biology. We have shown how these fatty acids affect brain growth, and revealed its molecular and cellular mechanisms. In particular, the reduced thickness of the cortex is due to precocious gliogenesis following neurogenesis, which may include epoxide metabolites of omega-6 fatty acids.
ALS, Alzheimer's - Dementia, Author Interviews, JAMA, Multiple Sclerosis, Neurological Disorders, Stem Cells / 12.01.2016

[caption id="attachment_20586" align="alignleft" width="200"]Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs Prof. Dimitrios Karussis[/caption] MedicalResearch.com Interview with: Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs Medical Research: What is the background for this study? What are the main findings? Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD).  Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs).  These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases. Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with ALS.  The two trials featured in the article, a phase 1/2 and a phase 2a, studied the transplantation NurOwn cells in ALS patients.  These trials confirmed the excellent safety profile of NurOwn and suggest a clinically meaningful effect. The investigators used two well established clinical endpoints that measure disease activity in ALS, the Revised ALS Functional Rating Scale and Forced Vital Capacity, and were able demonstrate a slowing of disease activity in the period following treatment.
Author Interviews, Beth Israel Deaconess, CT Scanning, JAMA, Neurological Disorders, Stroke / 04.01.2016

[caption id="attachment_20409" align="alignleft" width="128"]Sandeep Kumar, MD Assistant Professor of Neurology Harvard Medical School Director, Inpatient Stroke Service Department of Neurology, Stroke Division Beth Israel Deaconess Medical Center Boston, MA 02215 Dr. Sandeep Kumar[/caption] MedicalResearch.com Interview with: Sandeep Kumar, MD Assistant Professor of Neurology Harvard Medical School Director, Inpatient Stroke Service Department of Neurology, Stroke Division Beth Israel Deaconess Medical Center Boston, MA 02215 Medical Research: What is the background for this study? What are the main findings? Dr. Kumar: Transient deficits that start suddenly and typically last for a few minutes to a few hours are the hallmark of a transient ischemic attack (TIA) or a minor ischemic stroke. In this single-center observational study, we have reported similar clinical presentation in some patients with intracerebral hemorrhage (ICH) that are difficult to distinguish from cerebral ischemia based only on clinical signs and symptoms.
Author Interviews, JAMA, Mental Health Research, MRI, Neurological Disorders / 12.12.2015

[caption id="attachment_20038" align="alignleft" width="110"]Stephane De Brito, PhD Birmingham Fellow School of Psychology Robert Aitken Building, Room 337a University of Birmingham UK Dr. De Brito[/caption] MedicalResearch.com Interview with: Stephane De Brito, PhD Birmingham Fellow School of Psychology Robert Aitken Building, Room 337a University of Birmingham  UK Medical Research: What is the background for this study? What are the main findings? Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date. Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems.
Author Interviews, Epilepsy, Technology / 11.12.2015

MedicalResearch.com Interview with: Dr. Frances Hutchings Interdisciplinary Computing and Complex BioSystems School of Computing Science, Newcastle University Newcastle upon Tyne, United Kingdom Medical Research: What is the background for this study? Response: Temporal lobe epilepsy is a prevalent and disruptive disorder, which is often treated with surgical removal of epileptic tissue when medication fails to repress seizures. In around a third of cases surgery is unsuccessful at preventing seizures. The aim of this study is to seek ways to improve surgery success rates by giving a better prediction of where seizures are starting and spreading on an individual patient basis, using an individual’s brain imaging data. Surgery is simulated in the model to provide a prediction of a procedures effectiveness at reducing seizures. Medical Research: What are the main findings? Response: Using patient Diffusion Tensor Imaging data to reconstruct the brain as a network, locations commonly implicated in temporal lobe epilepsy were found by the model to be most vulnerable to seizures. Simulations of surgery (following a commonly used surgery procedure) in patient models predicted a surgery success rate close to 70%, matching clinical observations. Subject specific surgery simulations were also tried, following individual predictions from the model of which regions to remove for which person. These showed far greater improvements in seizure likelihood than regular surgery. This is a preliminary study and there is much to be done to improve the predictive success, and also to ensure that model predicted subject specific surgery regions are safe to remove. Nonetheless it is a significant move towards computer aided patient specific surgery planning to improve outcomes.
Author Interviews, Multiple Sclerosis / 07.12.2015

[caption id="attachment_19879" align="alignleft" width="133"]Dr. Vittorio Gallo PhD Center for Neuroscience Research Children’s Research Institute Children’s National Medical Center Washington, DC 20010 Dr. Vittorio Gallo[/caption] MedicalResearch.com Interview with: Dr. Vittorio Gallo PhD Center for Neuroscience Research Children’s Research Institute Children’s National Medical Center Washington, DC 20010 Medical Research: What is the background for this study? What are the main findings? Dr. Gallo: Astrocytes are cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, and help maintain homeostasis. In many neurodegenerative disorders – including multiple sclerosis  (MS) –astrocytes undergo a cellular and biochemical transformation called reactive gliosis. This process significantly impacts – both positively and negatively – neural regeneration. Reactive astrocytes (RAs) synthesize and release a peptide called Endothelin-1 (ET-1). Gallo and his team previously demonstrated that ET-1 is expressed at high levels by RAs in multiple sclerosis (MS) lesions and that – in animal models of MS – this peptide inhibits repair by delaying oligodendrocyte maturation and remyelination.  The main finding of the study published in Cell Reports is the identification of the cellular and molecular pathway that mediates the inhibitory effects of ET-1 on oligodendrocyte regeneration and remyelinaton in demyelinated lesions. In particular - by using pharmacological and genetic approaches - the study demonstrates that the ET-1 acts selectively through the ET-receptor B (ENDRB) on astrocytes - and not oligodendrocytes - to indirectly inhibit remyelination.
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

[caption id="attachment_19869" align="alignleft" width="150"]Professor Rhonda Voskuhl, M.D. Jack H. Skirball Chair in MS Research Director of the UCLA MS Program David Geffen School of Medicine University of California, Los Angeles Prof. Voskuhl[/caption] MedicalResearch.com Interview with: Professor Rhonda Voskuhl, M.D. Jack H. Skirball Chair in MS Research Director of the UCLA MS Program David Geffen School of Medicine University of California, Los Angeles Medical Research: What is the background for this study? What are the main findings? Dr. Voskuhl: It had been known for decades that relapses were reduced during pregnancy in women with Multiple Sclerosis (MS), psoriasis and rheumatoid arthritis. We viewed this as a major clue to help find new disease modifying treatments. Focusing on MS, we investigated treatment with estriol, an estrogen that is made by the fetus/placenta during pregnancy. Preclinical studies and a pilot clinical trial at UCLA showed good results leading to the current Phase 2 clinical trial at 16 sites across the U.S. It showed that treatment with estriol pills compared to placebo pills, each in combination with standard of care (glatirmar acetate) injections, reduced relapses by one third to one half over and above standard of care treatment.
Author Interviews, Genetic Research, Heart Disease, Neurological Disorders, NIH, Science / 05.12.2015

[caption id="attachment_19827" align="alignleft" width="106"]Jonathan Kaltman, MD Chief, Heart Development and Structural Diseases Branch Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute Dr. Kaltman[/caption] MedicalResearch.com Interview with: Jonathan Kaltman, MD Chief, Heart Development and Structural Diseases Branch Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute Medical Research: What are the main findings? Dr. Kaltman:  Congenital heart disease (CHD) is the most common birth defect but the cause for most defects is unknown.  Surgery and clinical care of patients with congenital heart disease has improved survival but now we are learning that many patients have neurodevelopmental abnormalities, including learning disability and attention/behavioral issues. Medical Research:  What are the main findings?
  • Using exome sequencing we found that patients with  congenital heart disease have a substantial number of de novo mutations.  This finding is especially strong in patients with CHD and another structural birth defect and/or neurodevelopmental abnormalities.
  • Many of the genes identified are known to be expressed in both the heart and the brain, suggesting a single mutation may contribute to both congenital heart disease and neurodevelopmental abnormalities.
Author Interviews, Brain Injury, Mayo Clinic, Neurological Disorders / 02.12.2015

[caption id="attachment_19745" align="alignleft" width="125"]Kevin Bieniek Kevin Bieniek[/caption] MedicalResearch.com Interview with: Kevin Bieniek B.Sc. Biology and Psychology Neuroscience researcher Mayo Clinic’s campus in Florida.  Medical Research: What is the background for this study? What are the main findings? Response:  Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury often sustained through contact sports and military blast exposure.  While CTE was first described in boxers in the 1920s, to date many descriptions of CTE have been made in high-profile professional athletes, but the frequency of Chronic traumatic encephalopathy pathology in athletes with more modest contact sports participation is unknown.  For this study, researchers at the Mayo Clinic in Jacksonville, FL examined the Mayo Clinic Brain Bank, one of the largest brain banks of neurodegenerative diseases.  In searching through medical records of over 1,700 patients, 66 individuals with clinically-documented contact sports participation were identified.  Of these 66 former athletes, 21 or 32% had pathologic changes in their brains consistent with CTE.  By comparison, none of 198 control individuals that did not have contact sports documentation in their medical records (including 66 women) had CTE pathology.  These results have been recently published in the December issue of the journal Acta Neuropathologica <<hyperlink: http://www.springer.com/medicine/pathology/journal/401.